The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain).
The characteristic three-dimensional shape of a molecule.
The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to alpha helices, beta strands (which align to form beta sheets) or other types of coils. This is the first folding level of protein conformation.
A change from planar to elliptic polarization when an initially plane-polarized light wave traverses an optically active medium. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
A rigorously mathematical analysis of energy relationships (heat, work, temperature, and equilibrium). It describes systems whose states are determined by thermal parameters, such as temperature, in addition to mechanical and electromagnetic parameters. (From Hawley's Condensed Chemical Dictionary, 12th ed)
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
A research technique to measure solvent exposed regions of molecules that is used to provide insight about PROTEIN CONFORMATION.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
Measurement of the intensity and quality of fluorescence.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
The method of measuring the dispersion of an optically active molecule to determine the relative magnitude of right- or left-handed components and sometimes structural features of the molecule.
Disruption of the non-covalent bonds and/or disulfide bonds responsible for maintaining the three-dimensional shape and activity of the native protein.
Spectroscopic method of measuring the magnetic moment of elementary particles such as atomic nuclei, protons or electrons. It is employed in clinical applications such as NMR Tomography (MAGNETIC RESONANCE IMAGING).
The rate dynamics in chemical or physical systems.
The homogeneous mixtures formed by the mixing of a solid, liquid, or gaseous substance (solute) with a liquid (the solvent), from which the dissolved substances can be recovered by physical processes. (From Grant & Hackh's Chemical Dictionary, 5th ed)
A low-energy attractive force between hydrogen and another element. It plays a major role in determining the properties of water, proteins, and other compounds.
A non-crystalline form of silicon oxide that has absorptive properties. It is commonly used as a desiccating agent and as a stationary phase for CHROMATOGRAPHY. The fully hydrated form of silica gel has distinct properties and is referred to as SILICIC ACID.
The property of objects that determines the direction of heat flow when they are placed in direct thermal contact. The temperature is the energy of microscopic motions (vibrational and translational) of the particles of atoms.
The normality of a solution with respect to HYDROGEN ions; H+. It is related to acidity measurements in most cases by pH = log 1/2[1/(H+)], where (H+) is the hydrogen ion concentration in gram equivalents per liter of solution. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
A conjugated protein which is the oxygen-transporting pigment of muscle. It is made up of one globin polypeptide chain and one heme group.
Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.
A computer simulation developed to study the motion of molecules over a period of time.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Analysis of the intensity of Raman scattering of monochromatic light as a function of frequency of the scattered light.
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
An essential amino acid that is necessary for normal growth in infants and for NITROGEN balance in adults. It is a precursor of INDOLE ALKALOIDS in plants. It is a precursor of SEROTONIN (hence its use as an antidepressant and sleep aid). It can be a precursor to NIACIN, albeit inefficiently, in mammals.
Computer-based representation of physical systems and phenomena such as chemical processes.
NMR spectroscopy on small- to medium-size biological macromolecules. This is often used for structural investigation of proteins and nucleic acids, and often involves more than one isotope.
A class of organic compounds which contain an anilino (phenylamino) group linked to a salt or ester of naphthalenesulfonic acid. They are frequently used as fluorescent dyes and sulfhydryl reagents.
The characteristic 3-dimensional shape and arrangement of multimeric proteins (aggregates of more than one polypeptide chain).
A spectroscopic technique in which a range of wavelengths is presented simultaneously with an interferometer and the spectrum is mathematically derived from the pattern thus obtained.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
Proteins prepared by recombinant DNA technology.
The ability of a protein to retain its structural conformation or its activity when subjected to physical or chemical manipulations.
Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are linear polypeptides that are normally synthesized on RIBOSOMES.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
A clear, odorless, tasteless liquid that is essential for most animal and plant life and is an excellent solvent for many substances. The chemical formula is hydrogen oxide (H2O). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
The naturally occurring or experimentally induced replacement of one or more AMINO ACIDS in a protein with another. If a functionally equivalent amino acid is substituted, the protein may retain wild-type activity. Substitution may also diminish, enhance, or eliminate protein function. Experimentally induced substitution is often used to study enzyme activities and binding site properties.
A basic enzyme that is present in saliva, tears, egg white, and many animal fluids. It functions as an antibacterial agent. The enzyme catalyzes the hydrolysis of 1,4-beta-linkages between N-acetylmuramic acid and N-acetyl-D-glucosamine residues in peptidoglycan and between N-acetyl-D-glucosamine residues in chitodextrin. EC
The protein components of a number of complexes, such as enzymes (APOENZYMES), ferritin (APOFERRITINS), or lipoproteins (APOLIPOPROTEINS).
The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds.
The first chemical element in the periodic table. It has the atomic symbol H, atomic number 1, and atomic weight [1.00784; 1.00811]. It exists, under normal conditions, as a colorless, odorless, tasteless, diatomic gas. Hydrogen ions are PROTONS. Besides the common H1 isotope, hydrogen exists as the stable isotope DEUTERIUM and the unstable, radioactive isotope TRITIUM.
Small proteinaceous infectious particles which resist inactivation by procedures that modify NUCLEIC ACIDS and contain an abnormal isoform of a cellular protein which is a major and necessary component. The abnormal (scrapie) isoform is PrPSc (PRPSC PROTEINS) and the cellular isoform PrPC (PRPC PROTEINS). The primary amino acid sequence of the two isoforms is identical. Human diseases caused by prions include CREUTZFELDT-JAKOB SYNDROME; GERSTMANN-STRAUSSLER SYNDROME; and INSOMNIA, FATAL FAMILIAL.
A strong organic base existing primarily as guanidium ions at physiological pH. It is found in the urine as a normal product of protein metabolism. It is also used in laboratory research as a protein denaturant. (From Martindale, the Extra Pharmacopoeia, 30th ed and Merck Index, 12th ed) It is also used in the treatment of myasthenia and as a fluorescent probe in HPLC.
Liquids that dissolve other substances (solutes), generally solids, without any change in chemical composition, as, water containing sugar. (Grant & Hackh's Chemical Dictionary, 5th ed)
Rhodopsins found in the PURPLE MEMBRANE of halophilic archaea such as HALOBACTERIUM HALOBIUM. Bacteriorhodopsins function as an energy transducers, converting light energy into electrochemical energy via PROTON PUMPS.
Spectrophotometry in the infrared region, usually for the purpose of chemical analysis through measurement of absorption spectra associated with rotational and vibrational energy levels of molecules. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
The accumulation of an electric charge on a object
Determination of the spectra of ultraviolet absorption by specific molecules in gases or liquids, for example Cl2, SO2, NO2, CS2, ozone, mercury vapor, and various unsaturated compounds. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
Condensation products of aromatic amines and aldehydes forming azomethines substituted on the N atom, containing the general formula R-N:CHR. (From Grant & Hackh's Chemical Dictionary, 5th ed)
Proteins found in any species of bacterium.
A fibrous protein complex that consists of proteins folded into a specific cross beta-pleated sheet structure. This fibrillar structure has been found as an alternative folding pattern for a variety of functional proteins. Deposits of amyloid in the form of AMYLOID PLAQUES are associated with a variety of degenerative diseases. The amyloid structure has also been found in a number of functional proteins that are unrelated to disease.
The study of PHYSICAL PHENOMENA and PHYSICAL PROCESSES as applied to living things.
The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.
The thermodynamic interaction between a substance and WATER.
Large, hoofed mammals of the family EQUIDAE. Horses are active day and night with most of the day spent seeking and consuming food. Feeding peaks occur in the early morning and late afternoon, and there are several daily periods of rest.
Deuterium. The stable isotope of hydrogen. It has one neutron and one proton in the nucleus.
Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.
The process by which two molecules of the same chemical composition form a condensation product or polymer.
The physical characteristics and processes of biological systems.
The formation of crystalline substances from solutions or melts. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
The measurement of the amplitude of the components of a complex waveform throughout the frequency range of the waveform. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
The pressure due to the weight of fluid.
An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.
Compounds and molecular complexes that consist of very large numbers of atoms and are generally over 500 kDa in size. In biological systems macromolecular substances usually can be visualized using ELECTRON MICROSCOPY and are distinguished from ORGANELLES by the lack of a membrane structure.
A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task.
A type of FLUORESCENCE SPECTROSCOPY using two FLUORESCENT DYES with overlapping emission and absorption spectra, which is used to indicate proximity of labeled molecules. This technique is useful for studying interactions of molecules and PROTEIN FOLDING.
A group of genetic, infectious, or sporadic degenerative human and animal nervous system disorders associated with abnormal PRIONS. These diseases are characterized by conversion of the normal prion protein to an abnormal configuration via a post-translational process. In humans, these conditions generally feature DEMENTIA; ATAXIA; and a fatal outcome. Pathologic features include a spongiform encephalopathy without evidence of inflammation. The older literature occasionally refers to these as unconventional SLOW VIRUS DISEASES. (From Proc Natl Acad Sci USA 1998 Nov 10;95(23):13363-83)
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Presence of warmth or heat or a temperature notably higher than an accustomed norm.
Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).
A serine endopeptidase secreted by the pancreas as its zymogen, CHYMOTRYPSINOGEN and carried in the pancreatic juice to the duodenum where it is activated by TRYPSIN. It selectively cleaves aromatic amino acids on the carboxyl side.
The process of cleaving a chemical compound by the addition of a molecule of water.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
The transfer of energy of a given form among different scales of motion. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed). It includes the transfer of kinetic energy and the transfer of chemical energy. The transfer of chemical energy from one molecule to another depends on proximity of molecules so it is often used as in techniques to measure distance such as the use of FORSTER RESONANCE ENERGY TRANSFER.
The extent to which an enzyme retains its structural conformation or its activity when subjected to storage, isolation, and purification or various other physical or chemical manipulations, including proteolytic enzymes and heat.
The art or process of comparing photometrically the relative intensities of the light in different parts of the spectrum.
The study of CHEMICAL PHENOMENA and processes in terms of the underlying PHYSICAL PHENOMENA and processes.
The physical phenomena describing the structure and properties of atoms and molecules, and their reaction and interaction processes.
Organic compounds containing the -CO-NH2 radical. Amides are derived from acids by replacement of -OH by -NH2 or from ammonia by the replacement of H by an acyl group. (From Grant & Hackh's Chemical Dictionary, 5th ed)
A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.
Proteins produced from GENES that have acquired MUTATIONS.
A family of cellular proteins that mediate the correct assembly or disassembly of polypeptides and their associated ligands. Although they take part in the assembly process, molecular chaperones are not components of the final structures.
A serine endopeptidase that is formed from TRYPSINOGEN in the pancreas. It is converted into its active form by ENTEROPEPTIDASE in the small intestine. It catalyzes hydrolysis of the carboxyl group of either arginine or lysine. EC
Organic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.
A mutation caused by the substitution of one nucleotide for another. This results in the DNA molecule having a change in a single base pair.
A mass spectrometry technique used for analysis of nonvolatile compounds such as proteins and macromolecules. The technique involves preparing electrically charged droplets from analyte molecules dissolved in solvent. The electrically charged droplets enter a vacuum chamber where the solvent is evaporated. Evaporation of solvent reduces the droplet size, thereby increasing the coulombic repulsion within the droplet. As the charged droplets get smaller, the excess charge within them causes them to disintegrate and release analyte molecules. The volatilized analyte molecules are then analyzed by mass spectrometry.
Variation in a population's DNA sequence that is detected by determining alterations in the conformation of denatured DNA fragments. Denatured DNA fragments are allowed to renature under conditions that prevent the formation of double-stranded DNA and allow secondary structure to form in single stranded fragments. These fragments are then run through polyacrylamide gels to detect variations in the secondary structure that is manifested as an alteration in migration through the gels.
A technique applicable to the wide variety of substances which exhibit paramagnetism because of the magnetic moments of unpaired electrons. The spectra are useful for detection and identification, for determination of electron structure, for study of interactions between molecules, and for measurement of nuclear spins and moments. (From McGraw-Hill Encyclopedia of Science and Technology, 7th edition) Electron nuclear double resonance (ENDOR) spectroscopy is a variant of the technique which can give enhanced resolution. Electron spin resonance analysis can now be used in vivo, including imaging applications such as MAGNETIC RESONANCE IMAGING.
An atom or group of atoms that have a positive or negative electric charge due to a gain (negative charge) or loss (positive charge) of one or more electrons. Atoms with a positive charge are known as CATIONS; those with a negative charge are ANIONS.
Proteins that contain an iron-porphyrin, or heme, prosthetic group resembling that of hemoglobin. (From Lehninger, Principles of Biochemistry, 1982, p480)
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
A type of scanning probe microscopy in which a probe systematically rides across the surface of a sample being scanned in a raster pattern. The vertical position is recorded as a spring attached to the probe rises and falls in response to peaks and valleys on the surface. These deflections produce a topographic map of the sample.
The color-furnishing portion of hemoglobin. It is found free in tissues and as the prosthetic group in many hemeproteins.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
A process that includes the determination of AMINO ACID SEQUENCE of a protein (or peptide, oligopeptide or peptide fragment) and the information analysis of the sequence.
Analysis based on the mathematical function first formulated by Jean-Baptiste-Joseph Fourier in 1807. The function, known as the Fourier transform, describes the sinusoidal pattern of any fluctuating pattern in the physical world in terms of its amplitude and its phase. It has broad applications in biomedicine, e.g., analysis of the x-ray crystallography data pivotal in identifying the double helical nature of DNA and in analysis of other molecules, including viruses, and the modified back-projection algorithm universally used in computerized tomography imaging, etc. (From Segen, The Dictionary of Modern Medicine, 1992)
A compound formed in the liver from ammonia produced by the deamination of amino acids. It is the principal end product of protein catabolism and constitutes about one half of the total urinary solids.
Agents that emit light after excitation by light. The wave length of the emitted light is usually longer than that of the incident light. Fluorochromes are substances that cause fluorescence in other substances, i.e., dyes used to mark or label other compounds with fluorescent tags.
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
The ability of a substance to be dissolved, i.e. to form a solution with another substance. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
The characteristic 3-dimensional shape of a carbohydrate.
Databases containing information about PROTEINS such as AMINO ACID SEQUENCE; PROTEIN CONFORMATION; and other properties.
An essential amino acid. It is often added to animal feed.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
Established cell cultures that have the potential to propagate indefinitely.
The scattering of x-rays by matter, especially crystals, with accompanying variation in intensity due to interference effects. Analysis of the crystal structure of materials is performed by passing x-rays through them and registering the diffraction image of the rays (CRYSTALLOGRAPHY, X-RAY). (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
A group of cytochromes with covalent thioether linkages between either or both of the vinyl side chains of protoheme and the protein. (Enzyme Nomenclature, 1992, p539)
A field of biology concerned with the development of techniques for the collection and manipulation of biological data, and the use of such data to make biological discoveries or predictions. This field encompasses all computational methods and theories for solving biological problems including manipulation of models and datasets.
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
Sites on an antigen that interact with specific antibodies.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.
One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.
Antibodies produced by a single clone of cells.
That portion of the electromagnetic spectrum in the visible, ultraviolet, and infrared range.
A metallic element of atomic number 30 and atomic weight 65.38. It is a necessary trace element in the diet, forming an essential part of many enzymes, and playing an important role in protein synthesis and in cell division. Zinc deficiency is associated with ANEMIA, short stature, HYPOGONADISM, impaired WOUND HEALING, and geophagia. It is known by the symbol Zn.
The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.
The sum of the weight of all the atoms in a molecule.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
Serum albumin from cows, commonly used in in vitro biological studies. (From Stedman, 25th ed)
Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA.
The branch of science that deals with the geometric description of crystals and their internal arrangement. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
The oxygen-carrying proteins of ERYTHROCYTES. They are found in all vertebrates and some invertebrates. The number of globin subunits in the hemoglobin quaternary structure differs between species. Structures range from monomeric to a variety of multimeric arrangements.
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Sequential operating programs and data which instruct the functioning of a digital computer.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
The process by which ELECTRONS are transported from a reduced substrate to molecular OXYGEN. (From Bennington, Saunders Dictionary and Encyclopedia of Laboratory Medicine and Technology, 1984, p270)
Transport proteins that carry specific substances in the blood or across cell membranes.
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which VEGETABLE PROTEINS is available.
Elements of limited time intervals, contributing to particular results or situations.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
A group of 13 or more deoxyribonucleotides in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.
A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN.
The assembly of the QUATERNARY PROTEIN STRUCTURE of multimeric proteins (MULTIPROTEIN COMPLEXES) from their composite PROTEIN SUBUNITS.
Proteins obtained from the species SACCHAROMYCES CEREVISIAE. The function of specific proteins from this organism are the subject of intense scientific interest and have been used to derive basic understanding of the functioning similar proteins in higher eukaryotes.
Chemical groups containing the covalent disulfide bonds -S-S-. The sulfur atoms can be bound to inorganic or organic moieties.
The modification of the reactivity of ENZYMES by the binding of effectors to sites (ALLOSTERIC SITES) on the enzymes other than the substrate BINDING SITES.
A non-aqueous co-solvent that serves as tool to study protein folding. It is also used in various pharmaceutical, chemical and engineering applications.
Scattering of a beam of electromagnetic or acoustic RADIATION, or particles, at small angles by particles or cavities whose dimensions are many times as large as the wavelength of the radiation or the de Broglie wavelength of the scattered particles. Also know as low angle scattering. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed) Small angle scattering (SAS) techniques, small angle neutron (SANS), X-ray (SAXS), and light (SALS, or just LS) scattering, are used to characterize objects on a nanoscale.
A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.
The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)
A representation, generally small in scale, to show the structure, construction, or appearance of something. (From Random House Unabridged Dictionary, 2d ed)
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.
The degree of 3-dimensional shape similarity between proteins. It can be an indication of distant AMINO ACID SEQUENCE HOMOLOGY and used for rational DRUG DESIGN.
Proteins obtained from ESCHERICHIA COLI.
Layers of lipid molecules which are two molecules thick. Bilayer systems are frequently studied as models of biological membranes.
A group of deoxyribonucleotides (up to 12) in which the phosphate residues of each deoxyribonucleotide act as bridges in forming diester linkages between the deoxyribose moieties.
A site on an enzyme which upon binding of a modulator, causes the enzyme to undergo a conformational change that may alter its catalytic or binding properties.
The measurement of the quantity of heat involved in various processes, such as chemical reactions, changes of state, and formations of solutions, or in the determination of the heat capacities of substances. The fundamental unit of measurement is the joule or the calorie (4.184 joules). (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)
A non-essential amino acid that is synthesized from GLUTAMIC ACID. It is an essential component of COLLAGEN and is important for proper functioning of joints and tendons.
Pairing of purine and pyrimidine bases by HYDROGEN BONDING in double-stranded DNA or RNA.
The phenomenon whereby certain chemical compounds have structures that are different although the compounds possess the same elemental composition. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)
Disruption of the secondary structure of nucleic acids by heat, extreme pH or chemical treatment. Double strand DNA is "melted" by dissociation of the non-covalent hydrogen bonds and hydrophobic interactions. Denatured DNA appears to be a single-stranded flexible structure. The effects of denaturation on RNA are similar though less pronounced and largely reversible.
Peptides composed of between two and twelve amino acids.
Particles consisting of aggregates of molecules held loosely together by secondary bonds. The surface of micelles are usually comprised of amphiphatic compounds that are oriented in a way that minimizes the energy of interaction between the micelle and its environment. Liquids that contain large numbers of suspended micelles are referred to as EMULSIONS.
The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)
The molecular designing of drugs for specific purposes (such as DNA-binding, enzyme inhibition, anti-cancer efficacy, etc.) based on knowledge of molecular properties such as activity of functional groups, molecular geometry, and electronic structure, and also on information cataloged on analogous molecules. Drug design is generally computer-assisted molecular modeling and does not include pharmacokinetics, dosage analysis, or drug administration analysis.
Reagents with two reactive groups, usually at opposite ends of the molecule, that are capable of reacting with and thereby forming bridges between side chains of amino acids in proteins; the locations of naturally reactive areas within proteins can thereby be identified; may also be used for other macromolecules, like glycoproteins, nucleic acids, or other.
A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases IMMUNITY, and provides energy for muscle tissue, BRAIN, and the CENTRAL NERVOUS SYSTEM.
A polynucleotide consisting essentially of chains with a repeating backbone of phosphate and ribose units to which nitrogenous bases are attached. RNA is unique among biological macromolecules in that it can encode genetic information, serve as an abundant structural component of cells, and also possesses catalytic activity. (Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)
Electron microscopy involving rapid freezing of the samples. The imaging of frozen-hydrated molecules and organelles permits the best possible resolution closest to the living state, free of chemical fixatives or stains.
Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.
An essential amino acid that is required for the production of HISTAMINE.
Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.
A basic science concerned with the composition, structure, and properties of matter; and the reactions that occur between substances and the associated energy exchange.
Single chains of amino acids that are the units of multimeric PROTEINS. Multimeric proteins can be composed of identical or non-identical subunits. One or more monomeric subunits may compose a protomer which itself is a subunit structure of a larger assembly.
The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.
A group of peptide antibiotics from BACILLUS brevis. Gramicidin C or S is a cyclic, ten-amino acid polypeptide and gramicidins A, B, D are linear. Gramicidin is one of the two principal components of TYROTHRICIN.
Protein modules with conserved ligand-binding surfaces which mediate specific interaction functions in SIGNAL TRANSDUCTION PATHWAYS and the specific BINDING SITES of their cognate protein LIGANDS.
The composition, conformation, and properties of atoms and molecules, and their reaction and interaction processes.
Physical motion, i.e., a change in position of a body or subject as a result of an external force. It is distinguished from MOVEMENT, a process resulting from biological activity.
Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.
The diversion of RADIATION (thermal, electromagnetic, or nuclear) from its original path as a result of interactions or collisions with atoms, molecules, or larger particles in the atmosphere or other media. (McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
The property of emitting radiation while being irradiated. The radiation emitted is usually of longer wavelength than that incident or absorbed, e.g., a substance can be irradiated with invisible radiation and emit visible light. X-ray fluorescence is used in diagnosis.
Measurement of the polarization of fluorescent light from solutions or microscopic specimens. It is used to provide information concerning molecular size, shape, and conformation, molecular anisotropy, electronic energy transfer, molecular interaction, including dye and coenzyme binding, and the antigen-antibody reaction.
Conformational transitions of the shape of a protein to various unfolded states.
The facilitation of biochemical reactions with the aid of naturally occurring catalysts such as ENZYMES.
A group of enzymes which catalyze the hydrolysis of ATP. The hydrolysis reaction is usually coupled with another function such as transporting Ca(2+) across a membrane. These enzymes may be dependent on Ca(2+), Mg(2+), anions, H+, or DNA.
The deductive study of shape, quantity, and dependence. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 6th ed)
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)
A sequence of amino acids in a polypeptide or of nucleotides in DNA or RNA that is similar across multiple species. A known set of conserved sequences is represented by a CONSENSUS SEQUENCE. AMINO ACID MOTIFS are often composed of conserved sequences.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Circular duplex DNA isolated from viruses, bacteria and mitochondria in supercoiled or supertwisted form. This superhelical DNA is endowed with free energy. During transcription, the magnitude of RNA initiation is proportional to the DNA superhelicity.
A computer simulation technique that is used to model the interaction between two molecules. Typically the docking simulation measures the interactions of a small molecule or ligand with a part of a larger molecule such as a protein.

Endocytosis: EH domains lend a hand. (1/52898)

A number of proteins that have been implicated in endocytosis feature a conserved protein-interaction module known as an EH domain. The three-dimensional structure of an EH domain has recently been solved, and is likely to presage significant advances in understanding molecular mechanisms of endocytosis.  (+info)

Membrane fusion: structure snared at last. (2/52898)

The structure of the core of the neuronal 'SNARE complex', involved in neurotransmitter release, has been determined recently. Its topological similarity to viral fusion proteins suggests how the SNARE complex might facilitate membrane fusion.  (+info)

Four dimers of lambda repressor bound to two suitably spaced pairs of lambda operators form octamers and DNA loops over large distances. (3/52898)

Transcription factors that are bound specifically to DNA often interact with each other over thousands of base pairs [1] [2]. Large DNA loops resulting from such interactions have been observed in Escherichia coli with the transcription factors deoR [3] and NtrC [4], but such interactions are not, as yet, well understood. We propose that unique protein complexes, that are not present in solution, may form specifically on DNA. Their uniqueness would make it possible for them to interact tightly and specifically with each other. We used the repressor and operators of coliphage lambda to construct a model system in which to test our proposition. lambda repressor is a dimer at physiological concentrations, but forms tetramers and octamers at a hundredfold higher concentration. We predict that two lambda repressor dimers form a tetramer in vitro when bound to two lambda operators spaced 24 bp apart and that two such tetramers interact to form an octamer. We examined, in vitro, relaxed circular plasmid DNA in which such operator pairs were separated by 2,850 bp and 2,470 bp. Of these molecules, 29% formed loops as seen by electron microscopy (EM). The loop increased the tightness of binding of lambda repressor to lambda operator. Consequently, repression of the lambda PR promoter in vivo was increased fourfold by the presence of a second pair of lambda operators, separated by a distance of 3,600 bp.  (+info)

Probing interactions between HIV-1 reverse transcriptase and its DNA substrate with backbone-modified nucleotides. (4/52898)

BACKGROUND: To gain a molecular understanding of a biochemical process, the crystal structure of enzymes that catalyze the reactions involved is extremely helpful. Often the question arises whether conformations obtained in this way appropriately reflect the reactivity of enzymes, however. Rates that characterize transitions are therefore compulsory experiments for the elucidation of the reaction mechanism. Such experiments have been performed for the reverse transcriptase of the type 1 human immunodeficiency virus (HIV-1 RT). RESULTS: We have developed a methodology to monitor the interplay between HIV-1 RT and its DNA substrate. To probe the protein-DNA interactions, the sugar backbone of one nucleotide was modified by a substituent that influenced the efficiency of the chain elongation in a characteristic way. We found that strand elongation after incorporation of the modified nucleotide follows a discontinuous efficiency for the first four nucleotides. The reaction efficiencies could be correlated with the distance between the sugar substituent and the enzyme. The model was confirmed by kinetic experiments with HIV-1 RT mutants. CONCLUSIONS: Experiments with HIV-1 RT demonstrate that strand-elongation efficiency using a modified nucleotide correlates well with distances between the DNA substrate and the enzyme. The functional group at the modified nucleotides acts as an 'antenna' for steric interactions that changes the optimal transition state. Kinetic experiments in combination with backbone-modified nucleotides can therefore be used to gain structural information about reverse transcriptases and DNA polymerases.  (+info)

A hyperstable collagen mimic. (5/52898)

BACKGROUND: Collagen is the most abundant protein in animals. Each polypeptide chain of collagen is composed of repeats of the sequence: Gly-X-Y, where X and Y are often L-proline (Pro) and 4(R)-hydroxy-L-proline (Hyp) residues, respectively. These chains are wound into tight triple helices of great stability. The hydroxyl group of Hyp residues contributes much to this conformational stability. The existing paradigm is that this stability arises from interstrand hydrogen bonds mediated by bridging water molecules. This model was tested using chemical synthesis to replace Hyp residues with 4(R)-fluoro-L-proline (Flp) residues. The fluorine atom in Flp residues does not form hydrogen bonds but does elicit strong inductive effects. RESULTS: Replacing the Hyp residues in collagen with Flp residues greatly increases triple-helical stability. The free energy contributed by the fluorine atom in Flp residues is twice that of the hydroxyl group in Hyp residues. The stability of the Flp-containing triple helix far exceeds that of any untemplated collagen mimic of similar size. CONCLUSIONS: Bridging water molecules contribute little to collagen stability. Rather, collagen stability relies on previously unappreciated inductive effects. Collagen mimics containing fluorine or other appropriate electron-withdrawing substituents could be the basis of new biomaterials for restorative therapies.  (+info)

How do peptide synthetases generate structural diversity? (6/52898)

Many low-molecular-weight peptides of microbial origin are synthesized nonribosomally on large multifunctional proteins, termed peptide synthetases. These enzymes contain repeated building blocks in which several defined domains catalyze specific reactions of peptide synthesis. The order of these domains within the enzyme determines the sequence and structure of the peptide product.  (+info)

Crystal structure of MHC class II-associated p41 Ii fragment bound to cathepsin L reveals the structural basis for differentiation between cathepsins L and S. (7/52898)

The lysosomal cysteine proteases cathepsins S and L play crucial roles in the degradation of the invariant chain during maturation of MHC class II molecules and antigen processing. The p41 form of the invariant chain includes a fragment which specifically inhibits cathepsin L but not S. The crystal structure of the p41 fragment, a homologue of the thyroglobulin type-1 domains, has been determined at 2.0 A resolution in complex with cathepsin L. The structure of the p41 fragment demonstrates a novel fold, consisting of two subdomains, each stabilized by disulfide bridges. The first subdomain is an alpha-helix-beta-strand arrangement, whereas the second subdomain has a predominantly beta-strand arrangement. The wedge shape and three-loop arrangement of the p41 fragment bound to the active site cleft of cathepsin L are reminiscent of the inhibitory edge of cystatins, thus demonstrating the first example of convergent evolution observed in cysteine protease inhibitors. However, the different fold of the p41 fragment results in additional contacts with the top of the R-domain of the enzymes, which defines the specificity-determining S2 and S1' substrate-binding sites. This enables inhibitors based on the thyroglobulin type-1 domain fold, in contrast to the rather non-selective cystatins, to exhibit specificity for their target enzymes.  (+info)

Structural basis of profactor D activation: from a highly flexible zymogen to a novel self-inhibited serine protease, complement factor D. (8/52898)

The crystal structure of profactor D, determined at 2.1 A resolution with an Rfree and an R-factor of 25.1 and 20.4%, respectively, displays highly flexible or disordered conformation for five regions: N-22, 71-76, 143-152, 187-193 and 215-223. A comparison with the structure of its mature serine protease, complement factor D, revealed major conformational changes in the similar regions. Comparisons with the zymogen-active enzyme pairs of chymotrypsinogen, trypsinogen and prethrombin-2 showed a similar distribution of the flexible regions. However, profactor D is the most flexible of the four, and its mature enzyme displays inactive, self-inhibited active site conformation. Examination of the surface properties of the N-terminus-binding pocket indicates that Ile16 may play the initial positioning role for the N-terminus, and Leu17 probably also helps in inducing the required conformational changes. This process, perhaps shared by most chymotrypsinogen-like zymogens, is followed by a factor D-unique step, the re-orientation of an external Arg218 to an internal position for salt-bridging with Asp189, leading to the generation of the self-inhibited factor D.  (+info)

TY - JOUR. T1 - Nucleotide-dependent conformational changes in the σ 54-dependent activator DctD. AU - Wang, Ying Kai. AU - Park, Sungdae. AU - Nixon, B. Tracy. AU - Hoover, Timothy R.. PY - 2003/10. Y1 - 2003/10. N2 - Activators of σ54-RNA polymerase holoenzyme couple ATP hydrolysis to formation of an open promoter complex. DctDΔ 1-142, a truncated and constitutively active form of the σ 54-dependent activator DctD from Sinorhizobium meliloti, displayed an altered DNase I footprint at its binding site located upstream of the dctA promoter in the presence of ATP. The altered footprint was not observed for a mutant protein with a substitution at or near the putative arginine finger, a conserved arginine residue thought to contact the nucleotide. These data suggest that structural changes in DctDΔ1-142 during ATP hydrolysis can be detected by alterations in the DNase I footprint of the protein and may be communicated by interactions between bound nucleotide and the arginine finger. In ...
Listing of all Polbase results with context for Reference: Nucleotide-dependent conformational change governs specificity and analog discrimination by HIV reverse transcriptase., Polymerase: HIV RT
Effects of fluorophore attachment on protein conformation and dynamics studied by spFRET and NMR. Related Articles Effects of fluorophore attachment
The following examples show how to set up alternate conformations for structure factor calculations as well as for empirical energy calculations. The first step is to append the alternate conformations to the current molecular structure file. In this particular case, one wants to generate alternate conformations for the side chains of residues 1 and 7. alternate.inp Now one has to go to the graphics and move the alternate conformations into the correct positions. In subsequent protocols, one has to insert the following statement after reading the molecular structure file ...
Roucan, M. and Kielmann, M. and Connon, S.J. and Bernhard, S.S.R. and Senge, M.O., Conformational control of nonplanar free base porphyrins: Towards bifunctional catalysts of tunable basicity, Chemical Communications, 54, 1, 2017, 26-29 ...
TY - JOUR. T1 - Comparative Visualization of the RNA Suboptimal Conformational Ensemble In Vivo. AU - Woods, Chanin T.. AU - Lackey, Lela. AU - Williams, Benfeard. AU - Dokholyan, Nikolay V.. AU - Gotz, David. AU - Laederach, Alain. N1 - Funding Information: This work was supported by the National Institutes of Health (NIH) under grant Nos. HL111527, GM101237, and HG008133 to A.L., grant Nos. R01 GM123238-01, 1R01GM123247, and R01 GM064803-12 to N.V.D., and grant No. 3R01GM080742-08S1 to B.W. L.L. was supported by an American Cancer Society ? Lee National Denim Day Postdoctoral Fellowship, grant No. PF-15-133-01-RMC. Publisher Copyright: © 2017 Biophysical Society Copyright: Copyright 2017 Elsevier B.V., All rights reserved.. PY - 2017/7/25. Y1 - 2017/7/25. N2 - When a ribonucleic acid (RNA) molecule folds, it often does not adopt a single, well-defined conformation. The folding energy landscape of an RNA is highly dependent on its nucleotide sequence and molecular environment. Cellular ...
TY - JOUR. T1 - Prediction of the receptor conformation for iGluR2 agonist binding. T2 - QM/MM docking to an extensive conformational ensemble generated using normal mode analysis. AU - Sander, Tommy. AU - Liljefors, Tommy. AU - Balle, Thomas. N1 - Keywords: Protein flexibility, molecular docking, normal mode analysis, elastic network model, ensemble generation, iGluR2 receptor, domain closure. PY - 2008. Y1 - 2008. KW - Former Faculty of Pharmaceutical Sciences. U2 - 10.1016/j.jmgm.2007.11.006. DO - 10.1016/j.jmgm.2007.11.006. M3 - Journal article. VL - 26. SP - 1259. EP - 1268. JO - Journal of Molecular Graphics and Modelling. JF - Journal of Molecular Graphics and Modelling. SN - 1093-3263. IS - 8. ER - ...
The accurate determination of a large number of protein structures by X-ray crystallography makes it possible to conduct a reliable statistical analysis of the distribution of the main-chain and side-chain conformational angles, how these are dependent on residue type, adjacent residue in the sequence, secondary structure, residue-residue interactions and location at the polypeptide chain termini. The interrelationship between the main-chain (phi, psi) and side-chain (chi 1) torsion angles leads to a classification of amino acid residues that simplify the folding alphabet considerably and can be a guide to the design of new proteins or mutational studies. Analyses of residues occurring with disallowed main-chain conformation or with multiple conformations shed some light on why some residues are less favoured in thermophiles. ...
DynDom is a program that determines protein domains, hinge axes and amino acid residues involved in the hinge bending. It is fully automated.. You can use DynDom if you have two conformations of the same protein. These may be two X-ray structures, or structures generated using simulation techniques such as molecular dynamics or normal mode analysis.. The application of DynDom provides a view of the conformational change that is easily understood. The conformational change may be quite complicated in detail, but by using DynDom you can visualize it as involving the movement of domains as quasi-rigid bodies. The analysis of a conformational change in terms of domain movements only makes sense if the interdomain deformation is at least comparable to the intradomain deformation. You can use DynDom to assess this, but the results could be misleading if this is not the case.. DynDom allows you to visualize the domain motion in terms of the rotation of one domain relative to another. Here we see the ...
Supplementary data for article: Grozdanovic, M. M.; Drakulić, B. J.; Gavrović-Jankulović, M. Conformational Mobility of Active and E-64-Inhibited Actinidin. Biochimica et Biophysica Acta: General Subjects 2013, 1830 (10), 4790-4799. ...
SWISS-MODEL Template Library (SMTL) entry for 1ht1. Nucleotide-Dependent Conformational Changes in a Protease-Associated ATPase HslU
Integrins undergo large‐scale conformational changes (Springer & Dustin, 2012). In the bent‐closed (BC) conformation, the integrin ectodomain folds at knees in the α‐ and β‐subunits so that the head and upper legs associate with the lower legs (Fig 1A). In two extended states, the extended‐closed (EC) and extended‐open (EO) conformations, extension of the α‐ and β‐knees raises the headpiece above the lower legs on cell surfaces (Fig 1A). In transition from EC to EO, that is, headpiece opening, the ligand‐binding metal ion‐dependent adhesion site (MIDAS) in the β‐subunit βI domain rearranges. This reshaping of the ligand‐binding site is linked by α‐helix pistoning within the βI domain to swing of the hybrid domain away from the integrin α‐subunit (Fig 1A). Although the affinities of these states have not yet been measured, previous studies have correlated integrin adhesiveness and high affinity for ligand with the EO conformation (Takagi et al, 2002, 2003; ...
As a member of the wwPDB, the RCSB PDB curates and annotates PDB data according to agreed upon standards. The RCSB PDB also provides a variety of tools and resources. Users can perform simple and advanced searches based on annotations relating to sequence, structure and function. These molecules are visualized, downloaded, and analyzed by users who range from students to specialized scientists.
TY - JOUR. T1 - DPD simulation of protein conformations. T2 - From α-helices to β-structures. AU - Vishnyakov, Aleksey. AU - Talaga, David S.. AU - Neimark, Alexander V.. PY - 2012/11/1. Y1 - 2012/11/1. N2 - We suggest a coarse-grained model for DPD simulations of polypeptides in solutions. The model mimics hydrogen bonding that stabilizes α-helical and β-structures using dissociable Morse bonds between quasiparticles representing the peptide groups amenable to hydrogen bonding. We demonstrate the capabilities of the model by simulating transitions between coil-like, globular, α-helical, and β-hairpin configurations of model peptides, varying Morse potential parameters, the hydrophobicities of residue side chains, and pH, which determines the charges of residue side chains. We construct a model triblock polypeptide mimicking the sequence of residues α-synuclein at two different pHs. The conformations of this model polypeptide depend on pH similarly to the behavior observed experimentally. ...
You searched for: Publisher American Chemical Society Remove constraint Publisher: American Chemical Society Subject Molecular Structure Remove constraint Subject: Molecular Structure Subject Protein Conformation Remove constraint Subject: Protein Conformation ...
The present study on the ATP-lid of HSP90, a pharmaceutically relevant oncology target is aimed at shedding light on the differences in conformational plasticity in the presence or absence of known fragments and small molecules. Unbiased, atomistic simulations in the upper microsecond range in explicit solvent will be used to generate a large number of conformational ensembles which will serve as a basis to address the conformational preferences in terms of the induced fit or the conformational selection concept. We expect to get useful atomistic insights for designing ligands which are able to freeze HSP90 in a particular conformation and therefore have a higher binding affinity and residence time. The project addresses the two extremes which underlie protein-ligand interactions, namely induced fit (1) and conformational selection (2). While in the former, binding is obtained by a specific structural change, the later selects the adequate protein conformation from the unbound ensemble. The ...
You searched for: Format Text Remove constraint Format: Text Subject Molecular Structure Remove constraint Subject: Molecular Structure Subject Protein Conformation Remove constraint Subject: Protein Conformation ...
When in a complex, a protein has bonds that mediate protein-protein interactions as well as those that maintain its own conformation. Upon force application, the dissociation of bonds between proteins in the complex competes with the dissociation of bonds within the protein, with the latter instance being favored as this allows the complex as a whole to maintain tension. This has been demonstrated using actin, filamin and a-actinin [1].. A change in conformation can be explained as a transition between two energy minima that are separated by a high energy state that slows down the transition [2]. Applied force favors this transition by lowering the energy requirement and altering the energy minima i.e. stabilizing the new conformation [3] (see figure below). Thus conformational changes are therefore dependent on force sensing, in terms of both the magnitude and duration of the detected force [4],[5]. The conformational changes pass the signal onto neighboring molecules by exposing catalytic ...
Another example of the initial conformer affecting systematic results can be found by inspecting an 8 member carbon chain: C1-C2-C3-C4-C5-C6-C7-C8. For illustrative purposes consider the central C4-C5 bond as we rotate it 360 degrees; from -180 to 180 degrees. If one starts in the all trans conformation, we find that as we rotate the C4-C5 bond the final conformation of 360 degrees is identical to the initial at 0 degrees. However, if the initial conformation had a number of kinks in it, we might discover that at the 120 degree mark, the C1 and C8 ran into each other. To relieve this steric problem the other dihedral angles, will relax, likely changing by more than 100 degrees and falling into new energy wells. As we continue the coordinate driving of the central C4-C5 angle to trans (180), we might find that the final conformation is not the same as the initial conformation because these other dihedrals have changed ...
Bustos, Paula, Gabriel Garber, and Jacopo Ponticelli. 2020. Capital Accumulation and Structural Transformation. The Quarterly Journal of Economics. 135(2): 1037-1094.
Obstructing conformational shifts in active proteins keeps therapeutic guarantee biologically. of taxol in vitro and in a xenograft style of lung tumor. Also the expected mode of actions of the energetic peptides was experimentally confirmed. Both peptides destined to their mother or father protein and their natural activity was abolished in the current presence of the peptides related towards the counterpart helices. These data demonstrate a uncharacterized way for rational style of proteins antagonists previously. displays the experimentally-derived get in touch with map of HIV-1 gp41 as extracted from PDB 1ENV. The helix-helix relationships can be recognized with a peak in the total value from the Fourier transform of the get in touch with map when used on the amount by rows (or individually by columns) from the relevant 21 × 21 operating submatrix. Fig. 1illustrates the Fourier transform related to the amount of rows representing the discussion between two 21-mer sections focused around ...
iomolecules can play a significant role in the formation of nanostructured hard tissues in living organisms. These materials are formed with a degree of control that cannot yet be exerted in synthetic laboratories. To mimic these natural biomineralisation strategies, we must identify the mechanisms at work at the biomolecule-mineral interface. We will investigate, via a coupling of theory and experiment, two aspects of this interface. One aspect is how the surface can manipulate the conformation of the adsorbing biomolecule. Conformationally-labile biomolecules such as intrinsically-disordered proteins (IDPs) can change conformation upon exposure to external stimuli. Mineral surfaces provide such a stimulus that can induce folding and thus confer function(s) (such as polymorph stabilisation) related to this new conformation. Another aspect is how the adsorption of biomolecules influences the growth/stability of different crystal faces. Harnessing the ability of biomolecules to modify the growth ...
div class=citation vocab=,,i class=fa fa-external-link-square fa-fw,,/i, Data from ,span resource= typeof=Enumeration,,span property=name,,a href=,Protein Conformation,/a,,/span, - ,span property=offers typeOf=Offer,,span property=offeredBy typeof=Library ll:Library resource=,,span property=name,,a property=url href=,Rensselaer Libraries,/a,,/span,,/span,,/span,,/span,,/div ...
apply FastRelax and measure rotamer recovery for each residue Implements protocols::rotamer_recovery::RRProtocol.. References core::conformation::Residue::atom_is_backbone(), cartesian_, core::id::D, protocols::relax::generate_relax_from_cmd(), core::conformation::Residue::is_virtual(), protocols::rotamer_recovery::RRProtocol::measure_rotamer_recovery(), core::conformation::Residue::natoms(), nonideal_, core::pack::task::PackerTask::pack_residue(), protocols::antibody::design::relax, core::pose::Pose::replace_residue(), core::pose::Pose::residue(), core::conformation::Residue::set_chi(), core::pose::Pose::size(), and core::id::THETA.. ...
The FCC has quietly revealed what amounts to a core componenet of its methodology for repacking TV channels in the post-incentive auction spectrum band.
1P1U: Tuning activation of the AMPA-sensitive GluR2 ion channel by genetic adjustment of agonist-induced conformational changes.
Increase in Affinity for ATP and change in E1-E2 Conformational Equilibrium after mutations to the phosphorylation site (Asp369) of the α subunit of Na,K-ATPase ...
Many DNA-binding proteins (DBPs) undergo a conformational transition upon binding to cognate sites. In some cases this transition is accomplished by folding of a natively unfolded region. What is the role of this conformational transition? The
A model for the bent conformation responsible for the regulation of the initial step of filament assembly. We propose that regulation of the initial step of fil
Structural Views on Extracellular Recognition and Conformational Modifications of A number of Sort-I Transmembrane Receptors Sort-I transmembrane proteins characterize a big group of 1,412 proteins in people with a large number of… Read more ». ...
Please be VERY careful with this particular assay for conformational change. Not only can a protease sensitive site be uncovered by a structural change, but also a ligand-less protein CAN be more breathe-able with respect to its liganded strucuture which can have a more solid protease protected structure. Typsin can be very sneakey if given the chance. This happened to us. Turns out that by X-ray analysis and by NMR analysis, what was previously thought of as a structural change on ligand binding was actually a firming up of the fold of the protein. No residues actually changed position to any great extend. The protease protection is probably a red herring in this case. There are very well documented examples of protease protection revealing gross structural changes. Just...PLEASE BE CAREFUL with the interpretation of this assay ...
The influence of the range of the involved geometric and material parameters, such as the available area for conformational changes, the bilayer thickness, the interaction energy between transmembrane domains and lipids, is largely explored. Bounds on the available conformations experienced by the transmebrane domains are also provided.
H CHOP780101 D Normalized frequency of beta-turn (Chou-Fasman, 1978a) R LIT:2004003a PMID:354496 A Chou, P.Y. and Fasman, G.D. T Empirical predictions of protein conformation J Ann. Rev. Biochem. 47, 251-276 (1978) C PALJ810106 0.977 TANS770110 0.956 CHAM830101 0.946 CHOP780203 0.940 CHOP780216 0.929 CHOP780210 0.921 ROBB760113 0.907 GEIM800108 0.899 QIAN880133 0.897 QIAN880132 0.896 LEVM780103 0.893 PRAM900104 0.891 LEVM780106 0.890 ROBB760108 0.887 BEGF750103 0.885 ISOY800103 0.885 CRAJ730103 0.882 GEIM800111 0.878 PALJ810105 0.868 ROBB760110 0.863 NAGK730103 0.827 QIAN880131 0.824 AURR980114 -0.803 BEGF750101 -0.803 QIAN880107 -0.809 KANM800103 -0.824 AURR980109 -0.837 SUEM840101 -0.845 I A/L R/K N/M D/F C/P Q/S E/T G/W H/Y I/V 0.66 0.95 1.56 1.46 1.19 0.98 0.74 1.56 0.95 0.47 0.59 1.01 0.60 0.60 1.52 1.43 0.96 0.96 1.14 0.50 // H CHOP780201 D Normalized frequency of alpha-helix (Chou-Fasman, 1978b) R PMID:364941 A Chou, P.Y. and Fasman, G.D. T Prediction of the secondary structure of ...
The formation of complexes that have large interfaces is seen to involve large changes in conformation in those cases where native structures are available. These changes are generally described in publications reporting the X-ray structure of the complexes. They are summarised in Table 2 for the 20 complexes that have B,2000 Å^2. B=interface ...
A protein is a linear chain of amino acids that folds into a unique functional structure, called its native state. In this state, proteins show repeated substructures like alpha helices and beta sheet
Dynamic Conformational Behavior and Molecular Interaction Discrimination of DNA/Binder Complexesby Single-Chain Stretching in a MicroDevice ...
List of words make out of Conformational. All anagrams of Conformational. Words made after unscrambling Conformational. Scrabble Points. Puzzle Solver. Word Creation.
The occupancy of ions in the K+ selectivity filter: Charge balance and coupling of ion binding to a protein conformational change underlie high conduction ...
The occupancy of ions in the K+ selectivity filter: Charge balance and coupling of ion binding to a protein conformational change underlie high conduction ...
Brookhaven Lab scientists and staff combine expertise across disciplines and use Labs unique facilities to address drug development, medical supplies, information processing, and more
Repairable NISSAN ALTIMA XE/ 1999 with primary damage FRONT END is for sale in BROOKHAVEN NY, Lot 28262325. VIN 1N4DL01DXXC261595
The structure of a molecule dictates its function. If you were to consider NAs, for example, they wouldnt be good enzymes since you only have a limited number of NA types as well as conformation. Which part of the NA would a reactant bind to? Same questions for CHOs and lipids. The way proteins are structured, you have so many conformations (recall 4 levels of structure) possible depending on composition. Variability in conformation among different protein molecules is important since conformation is critical in being able to bind with the reactants to enable catalysis of a reaction ...
Information about Brookhaven College CNA degrees. Nursing is one of the fastest-growing job areas, and for good reason. As the population ages, medical care will continue to expand rapidly.
Brookhaven Youth Ranch students can get immediate homework help and access over 100+ documents, study resources, practice tests, essays, notes and more.
Information about Brookhaven College RN degrees. Nursing is one of the fastest-growing job areas, and for good reason. As the population ages, medical care will continue to expand rapidly.
TY - JOUR. T1 - Electrostatic energy calculation on the pH-induced conformational change of influenza virus hemagglutinin. AU - Ho, Sup Choi. AU - Huh, June. AU - Won, Ho Jo. PY - 2006. Y1 - 2006. N2 - The pH-induced conformational change of influenza virus hemagglutinin (HA) has been investigated by calculating the change of electrostatic energy of the fragment of HA2 upon pH change. The average charge and electrostatic free energy are calculated as a function of pH for the fusion peptide (residues 1-20 of HA2) and the polypeptide of residues 54-77 of HA2 by using the finite difference Poisson-Boltzmann method. It is found that as pH decreases from 8 to 5, the electrostatic free energy of the fusogenic state is lowered by ∼2 kcal/mol and the fusogenic state is less ionized compared to that of the native state for both polypeptides. For the fusion peptide at the fusogenic state, most of ionizable residues are neutral at acidic pH except Glu-11. For the polypeptide of residues 54-77 at the ...
TY - GEN. T1 - Efficient algorithms to explore conformation spaces of flexible protein loops. AU - Dhanik, A.. AU - Yao, P.. AU - Marz, N.. AU - Propper, R.. AU - Kou, C.. AU - Liu, Guanfeng. AU - Van Den Bedem, H.. AU - Latombe, J. C.. PY - 2007. Y1 - 2007. N2 - Two efficient and complementary sampling algorithms are presented to explore the space of closed clash-free conformations of a flexible protein loop. The seed sampling algorithm samples conformations broadly distributed over this space, while the deformation sampling algorithm uses these conformations as starting points to explore more finely selected regions of the space. Computational results are shown for loops ranging from 5 to 25 residues. The algorithms are implemented in a toolkit, LoopTK, available at AB - Two efficient and complementary sampling algorithms are presented to explore the space of closed clash-free conformations of a flexible protein loop. The seed sampling algorithm samples ...
Check out our new paper and video on Protein-peptide molecular docking with large-scale conformational changes: the p53-MDM2 interaction. ...
Conformational characterisation of peptide-1 at 10°C in the presence of TFE and SDS (A). Far-UV CD spectra at pH 4.2 as a function of TFE concentration. TFE in
where TE-PLPclose is the holo tetrameric active Trpase at 25°C in a close conformation; TE-PLPopen is the holo tetrameric enzyme in the open conformation at 2°C; TE... PLP is the non-covalently bound complex in an open conformation and TE is the apo enzyme in an open conformation at 2°C. Step 4 is the dissociation of the tetrameric form to dimers, TE to DE.. Cooling (step 1) weakens the hydrophobic interactions resulting in a conformational change and a corresponding modified solvation. The change from the closed to an open conformation is associated with a reduction in the tight packing of the tetramer and is enhanced by the point mutations. This conformational change is further supported by the present high pressure studies showing that increasing hydrostatic pressure has the same effect as decreasing temperature in affecting the conformational equilibrium.. The conformational change at low temperatures results in breaking the covalent aldimine bond between residue Lys270 (E. coli ...
Human type II transglutaminase (TG2) is an enzyme that exists in two dramatically different conformational states, each with a unique activity. In the open, extended form, the transglutaminase active site is exposed, allowing TG2 to catalyze formation of an isopeptide bond between the sidechain of a peptide-bound glutamine and a primary amine. Upon GTP binding to a separate GTPase active site, TG2 adopts a heavily favored and compact closed conformation, which obstructs the glutaminase active site, and only allows GTPase activity. TG2 has been linked to Huntingtons disease, as well as to many other cellular processes, both physiological and pathological. However, TG2s two conformational states, each with its own activity, have made it difficult to elucidate how this enzyme functions in disease progression. In addition, because TG2 heavily prefers the closed state, attempts to screen for inhibitors that may bind the transglutanimase site exposed in the open conformation, and attempts to obtain ...
Close The Infona portal uses cookies, i.e. strings of text saved by a browser on the users device. The portal can access those files and use them to remember the users data, such as their chosen settings (screen view, interface language, etc.), or their login data. By using the Infona portal the user accepts automatic saving and using this information for portal operation purposes. More information on the subject can be found in the Privacy Policy and Terms of Service. By closing this window the user confirms that they have read the information on cookie usage, and they accept the privacy policy and the way cookies are used by the portal. You can change the cookie settings in your browser. ...
Accurate predictions of pKa values of titratable groups require taking into account all relevant processes associated with the ionization/deionization. Frequently, however, the ionization does not involve significant structural changes and the dominating effects are purely electrostatic in origin allowing accurate predictions to be made based on the electrostatic energy difference between ionized and neutral forms alone using a static structure. On another hand, if the change of the charge state is accompanied by a structural reorganization of the target protein, then the relevant conformational changes have to be taken into account in the pKa calculations. Here we report a hybrid approach that first predicts the titratable groups, which ionization is expected to cause conformational changes, termed
Protein dynamics play a crucial role in function, catalytic activity, and pathogenesis. Consequently, there is great interest in computational methods that probe the conformational fluctuations of a protein. However, molecular dynamics simulations are computationally costly and therefore are often limited to comparatively short timescales. TYPHON is a probabilistic method to explore the conformational space of proteins under the guidance of a sophisticated probabilistic model of local structure and a given set of restraints that represent nonlocal interactions, such as hydrogen bonds or disulfide bridges. The choice of the restraints themselves is heuristic, but the resulting probabilistic model is well-defined and rigorous. Conceptually, TYPHON constitutes a null model of conformational fluctuations under a given set of restraints. We demonstrate that TYPHON can provide information on conformational fluctuations that is in correspondence with experimental measurements. TYPHON provides a ...
en] The cold-active phosphoglycerate kinase from the Antarctic bacterium Pseudomonas sp. TACII18 exhibits two distinct stability domains in the free, open conformation. It is shown that these stability domains do not match the structural N- and C-domains as the heat-stable domain corresponds to about 80 residues of the C-domain, including the nucleotide binding site, whereas the remaining of the protein contributes to the main heat-labile domain. This was demonstrated by spectroscopic and microcalorimetric analyses of the native enzyme, of its mutants, and of the isolated recombinant structural domains. It is proposed that the heat-stable domain provides a compact structure improving the binding affinity of the nucleotide, therefore increasing the catalytic efficiency at low temperatures. Upon substrate binding, the enzyme adopts a uniformly more stable closed conformation. Substrate-induced stability changes suggest that the free energy of ligand binding is converted into an increased ...
Understanding the conformational changes associated with the binding of small ligands to their biological targets is a fascinating and meaningful question in chemistry, biology and drug discovery. One of the most studied and important is the so-called DFG-flip of tyrosine kinases. The conserved three amino-acid DFG motif undergoes an in to out movement resulting in a particular inactive conformation to which type II kinase inhibitors, such as the anti-cancer drug Imatinib, bind. Despite many studies, the details of this prototypical conformational change are still debated. Here we combine various NMR experiments and surface plasmon resonance with enhanced sampling molecular dynamics simulations to shed light into the conformational dynamics associated with the binding of Imatinib to the proto-oncogene c-Src. We find that both conformational selection and induced fit play a role in the binding mechanism, reconciling opposing views held in the literature. Moreover, an external binding pose ...
Tel Aviv, Israel - March 18, 2008 - Compugen Ltd. (NASDAQ: CGEN) announced today the development and validation of its Blockers of Disease-Associated Conformation (DAC Blockers) platform, a new discovery platform for the identification of peptides that block proteins from adopting their disease-associated conformations. To date, two of the predicted therapeutic peptide candidates from the pilot validation run of the platform have shown initial experimental verification, one with anti-inflammatory and the other with anti-cancer activities.. The newly developed DAC Blockers platform has been designed to identify segments in proteins of interest that, if introduced therapeutically as synthetic peptides, would block specific conformational changes of such proteins, and thereby prevent them from adopting disease-associated conformations and related activities. A key capability of the platform is that it enables the proteome-wide search for such conformational change blocking peptides in human, viral ...
A procedure for automated protein structure determination is presented that is based on an iterative procedure during which the NOESY peak list assignment and the structure calculation are performed s
ClpB is a bacterial heat-shock protein that disaggregates and reactivates strongly aggregated proteins in cooperation with the DnaK chaperone system. ClpB contains two ATP-binding AAA+ modules, a linker coiled-coil domain, and a highly mobile N-terminal domain. It forms ring-shaped hexamers in a nucleotide-dependent manner. The unique aggregation reversing chaperone activity of ClpB involves ATP-dependent translocation of substrates through the central channel in the ClpB ring. The initial events of aggregate recognition and the events preceding the translocation step are poorly understood. In addition to the full-length ClpB95, a truncated isoform ClpB80, that is missing the whole N-terminal domain, is also produced in vivo. Various aspects of the structure and function of ClpB were addressed in this work. The thermodynamic stability of ClpB in its monomeric and oligomeric forms, as well as the nucleotide-induced conformational changes in ClpB were investigated by fluorescence spectroscopy. ...
Proteins are dynamic molecules. Even under native conditions, they do not adopt a single static conformation. Rather, they access many different conformations in their native state ensemble. This native state ensemble includes small fluctuations around the native conformation, partially unfolded forms, and even globally unfolded forms. The distribution of these conformations and the kinetic barriers between the conformational states define the conformational energy landscapes of proteins. My research interest is investigating conformational energy landscapes of proteins and deciphering the relationship between the energetics of proteins and their biochemical functions, such as catalysis, signal transduction, and ligand binding. We use proteolysis as a major tool to probe protein structures and dynamics as well as conventional spectroscopic methods. We also use proteomics extensively for investigating energy landscapes of proteins on a system level.. Investigation of conformational energy ...
Abstract: Biomolecular assemblies exhibit emergent behavior in both the temporal and spatial domains. As observed in long-timescale molecular dynamics simulations or in 3D models of large-scale biomolecular systems, the behavior that emerges on these scales is not only more than the sum of the (temporal or spatial) parts, but quite different and unexpected. Examples include: (1) slow conformational changes in protein folding and protein-protein binding enabled by fast motion in long molecular dynamics simulations; (2) the interpretation and refinement of intermediate-resolution electron microscopy (EM) structures using multiple or flexible atomic fragments; and (3) the segmentation of the molecular building blocks of living organisms in low-resolution data from EM or tomography. The unifying goal of our efforts is to observe and to take into account functional dynamics in the native environment (solution or vitreous ice) or in silico and then to reconstruct and interpret the 3D shapes of the ...
Proteins are highly dynamic macromolecules. To analyze their inherent flexibility, computational biologists often use molecular dynamics (MD) simulations. The quantification of protein flexibility is based on various methods such as Root Mean Square Fluctuations (RMSF) that rely on multiple MD snapshots or Normal Mode Analysis (NMA) that rely on a single structure and focus on quantifying large movements. Alternative in silico approaches assess protein motions through the protein residue network or dynamical correlations from MD simulations. An alternative yet powerful approach based on small prototypes or structural alphabets (SAs) can be used. SAs approximate conformations of protein backbones and code the local structures of proteins as one-dimensional sequences. Protein Blocks (PBs) are one of these SAs. Applying PB-based approaches to biological systems such as the DARC protein, the human αIIb β3 integrin and the KISSR1 protein highlighted the major interest of PBs in understanding local
Due to their long lifetime, triplet, redox and other transient states of fluorophores are highly sensitive to the micro-environment. Imaging their spatial distribution in biological samples can therefore help answer interesting questions about the metabolism, molecular interactions and dynamics in living cells. However, as these states are at best weakly luminescent, they have up to now only been used to a limited extent in life sciences. In Transient State (TRAST) imaging, the characteristic build up of transient states is instead monitored via fluorescence, as the excitation is modulated. When the illumination pulse width is step-wise increased, transient states are progressively populated. The resulting depletion of the singlet excited state can be monitored via time-averaged fluorescence. This fluorescence decay is characteristic for the transient state kinetics of the fluorophore in a given environment. Traditional fluorescence parameters can only be influenced within the lifetime of the ...
The present work is one of the first characterizations of multimeric intermediates in protein aggregation, and offers direct information about the assembly process. The results of the Ellman assay confirm that the dimer is linked by a disulfide bond, as previously proposed (Manderson et al. 1998; Bauer et al. 2000). Formation of the dimer therefore requires at least unfolding of the proteins main helix (Qi et al. 1997), which protects the free cysteine from the solvent in the native structure. We have previously shown that the Blg oligomers are productive intermediates in aggregation: assembly of aggregates coincides with consumption of oligomers, and purified oligomers at high concentration aggregate very rapidly (Bauer et al. 2000). The molten globule character of the oligomers observed here is perfectly in line with previous studies on other proteins (Booth et al. 1997; Kayed et al. 1999; McParland et al. 2000; Rochet and Lansbury 2000), demonstrating that aggregation is accelerated by ...
Equine conformation evaluates the degree of correctness of a horses bone structure, musculature, and its body proportions in relation to each other. Undesirable conformation can limit the ability to perform a specific task. Although there are several universal faults, a horses conformation is usually judged by what its intended use may be. Thus form to function is one of the first set of traits considered in judging conformation. A horse with poor form for a Grand Prix show jumper could have excellent conformation for a World Champion cutting horse, or to be a champion draft horse. Every horse has good and bad points of its conformation and many horses (including Olympic caliber horses) excel even with conformation faults. The standard of the ideal head varies dramatically from breed to breed based on a mixture of the role the horse is bred for and what breeders, owners and enthusiasts find appealing. Breed standards frequently cite large eyes, a broad forehead and a dry head-to-neck ...
Lets look at folding in another way: You might guess a protein would fold to lowest free energy conformation. Problem: is there time? (Levinthals Paradox, formulated by Cyrus Levinthal in 1968) Stryer calculation (very conservative): Assume 100 aa residue protein with 3 possible conformations/residue; then get 3100or 5 x 1047 possible conformations. If search at a rate of one structure/10-13sec then get (5 x 1047)(10-13)= 5 x 1034 sec or 1.6 x 1027 years to search (and thus to fold protein). This is greater than the age of our Universe (13.7 x 109 yrs). [Rawn calculation (perhaps more realistic): same but assume 10 conformations, then get 1087sec or 3 x 1080 yrs!]. Obviously from these calculations not searching all possible conformations (or we have the process wrong!), so cannot say protein achieves the lowest global free energy, but rather a local free energy minima. (Like a valley in mountain range: a local energy minima, but not lowest [Marianas trench].) [sketch - note represents ...
G protein-coupled receptors (GPCRs) are membrane proteins critical in cellular signaling, making them important targets for therapeutics. The activation of GPCRs is central to their function, requiring multiple conformations of the GPCRs in their activation landscape. To enable rational design of GPCR-targeting drugs, it is essential to obtain the ensemble of atomistic structures of GPCRs along their activation pathways. This is most challenging for structure determination experiments, making it valuable to develop reliable computational structure prediction methods. In particular, since the active-state conformations are higher in energy (less stable) than inactive-state conformations, they are difficult to stabilize. In addition, the computational methods are generally biased toward lowest energy structures by design and miss these high energy but functionally important conformations. To address this problem, we have developed a computationally efficient ActiveGEnSeMBLE method that ...
Solute effects arise from PREFERENTIAL INTERACTIONS (Timasheff): Solute and water compete for the biopolymer surface Preferential Accumulation of Solute: Solute-Biopolymer interactions more favorable than interactions of both species with water Local concentration of solute higher than bulk Preferential Exclusion of Solute (Preferential Hydration) Local concentration of solute lower than bulk To describe solute distribution: Schellman 1:1 solute: water competitive binding model Our solute partitioning model; partition coefficient K p K p = m 3 loc /m 3 bulk If K p > 1, solute is accumulated; if K p < 1, solute is excluded
The translation of personal genomics to precision medicine depends on the accurate interpretation of the multitude of genetic variants observed for each individual. However, even when genetic variants are predicted to modify a protein, their functional implications may be unclear. Many diseases are caused by genetic variants affecting important protein features, such as enzyme active sites or interaction interfaces. The scientific community has catalogued millions of genetic variants in genomic databases and thousands of protein structures in the Protein Data Bank. Mapping mutations onto three-dimensional (3D) structures enables atomic-level analyses of protein positions that may be important for the stability or formation of interactions; these may explain the effect of mutations and in some cases even open a path for targeted drug development. To accelerate progress in the integration of these data types, we held a two-day Gene Variation to 3D (GVto3D) workshop to report on the latest advances and to
Monoclonal antibodies have become essential tools to study the structure and function of integrins because they recognise distinct conformational states of the receptors (Mould, 1996). Many of these antibodies have been used to study changes in the ligand-binding affinity of integrins on the cell surface (Humphries, 2000); however, in this study, we used their specificities to report defined conformational states during β1-integrin biosynthesis. In particular, we noted that two conformation-specific antibodies, 8E3 and 9EG7, which have been shown to recognise the unbent form of β1-integrins, also react with monomeric β1-integrin subunits. 9EG7 was of particular interest because it seems to recognise an epitope that requires the formation of a disulphide and once this disulphide is formed, the epitope is not lost even after denaturation. The epitope has been mapped previously to within a cysteine-rich stretch (residues 495-602) at the back of the β1-integrin knee region (Bazzoni et al., ...
Supplementary MaterialsSupplementary Figures BCJ-474-2449-s1. replication. Thus, HIV-1 Tat appears to stabilise Mdm2, which in turn enhances Tat-mediated viral replication. This study highlights the importance of post-translational modifications of host cellular factors in HIV-1 replication and pathogenesis. and and and and assay using DNA-PK shows phosphorylation of p53 at S15 and S37, which interferes with the ability of Mdm2 to inhibit p53 transactivation. These phosphorylation events are known to cause conformational changes in p53, which leads to p53 stabilisation during DNA damage [29,30]. ATM phosphorylates p53 at S15 in response to DNA damage, whereas ATR phosphorylates p53 at S15 and S37 during genotoxic stress [31C33]. Studies in severe combined immunodeficiency (SCID) mice with defective DNA-PK show how the cells remain in a position to induce p53 and go through G1 arrest, recommending that ATM Erlotinib Hydrochloride kinase activity assay and ATR kinases get excited about the p53 S15 ...
The creation of an automated method for determining 3D protein structure would be invaluable to the eld of biology and presents an interesting challenge to computer science. Unfortunately , given the current level of protein knowledge, a completely automated solution method is not yet feasible; therefore, our group has decided to integrate existing databases and theories to create a software system that assists X-ray crystallographers in specifying a particular protein structure. By breaking the problem of determining overall protein structure into small subproblems, we hope to come closer to solving a novel structure by solving each component. By generating necessary information for structure determination, this method provides the rst step toward designing a program to determine protein conformation automatically. The properties of a protein are largely determined by its three-dimensional structure Voet and Voet 1990]. This statement would seem to simplify the process of understanding proteins and
PINK1‐mediated phosphorylation of Ub at Ser65 has dramatic consequences for Ub structure, and key processes in the Ub system, namely Ub attachment and removal.. It could be expected that phosphorylation of Ub would change its surface properties due to the addition of a negative charge. The obtained high‐resolution crystal structure and solution studies agree that the majority of phosphoUb is structurally similar to wt Ub. To our amazement, NMR studies showed a second, minor conformation of phosphoUb, which is in slow exchange with the major conformation. Strikingly, the minor conformation shows distinct hydrogen bonding patterns and long‐range NOEs for its C‐terminal β5‐strand, which can only be structurally satisfied when this strand is shifted by two residues. Our phosphoUbretraCT model explains numerous observations and is structurally feasible due to the existence of four Leu‐Xaa repeats in the β5‐strand that would allow a shift of two residues without significantly ...
Discovering the tertiary framework of the protein, or even the quaternary structure of its complexes, can offer significant clues about how the protein performs its function. Frequent experimental methods of composition dedication consist of X-ray crystallography and NMR spectroscopy, equally of which can produce facts at atomic resolution. Our site Even so, NMR experiments can deliver information from which a subset of distances among pairs of atoms may be approximated, and the ultimate achievable conformations for a protein are determined by solving a length geometry issue. Twin polarisation interferometry can be a quantitative analytical approach for measuring the overall protein conformation and conformational modifications due to interactions or other stimulus ...
The spatial and temporal control of self-assemblies is the latest scientific hurdle in supramolecular chemistry which is inspired by the functioning of biological systems fueled by chemical signals. In this study, we work towards alleviating this scenario by employing a unique amphiphilic foldamer that opera Celebrating the Chemical Science in India - Leaders in the Field Symposium
Background: Techniques for inferring the functions of the protein by comparing their shape similarity have been receiving a lot of attention. Proteins are functional units and their shape flexibility occupies an essential role in various biological processes. Several shape descriptors have demonstrated the capability of protein shape comparison by treating them as rigid bodies. But this may give rise to an incorrect comparison of flexible protein shapes. Results: We introduce an efficient approach for comparing flexible protein shapes by adapting a local diameter (LD) descriptor. The LD descriptor, developed recently to handle skeleton based shape deformations [1], is adapted in this work to capture the invariant properties of shape deformations caused by the motion of the protein backbone. Every sampled point on the protein surface is assigned a value measuring the diameter of the 3D shape in the neighborhood of that point. The LD descriptor is built in the form of a one dimensional histogram ...
Characterization of different conformational states of proteins is essential to understand their stability and activity. Biophysical techniques aid in analysing these conformational states and molecular fluorescence is one of the most reliable and quickly accessible methods. Apart from the intrinsic fluoresc
Purpose: Lacritin is a human tear glycoprotein that has high thermal stability. When cleaved, lacritin has antimicrobial activity resulting from the C-terminus amphipathic alpha helical region. The alpha helices contain three salt bridges; ionic bonds between neighboring oppositely charged amino acids. The purpose of this research was to investigate the hypothesis that the salt bridges within the alpha helices contribute to the high thermal stability. Methods: To determine the role of salt bridges in the thermal stability of lacritin, point mutants were prepared for each salt bridge by site directed mutagenesis that replaced the oppositely charged amino acids with serine. The point mutants were expressed in E. coli and purified. Western blot analysis confirmed the identity of lacritin proteins. Circular dichroism (CD) was used to study conformational changes in the secondary structure of these mutants compared to unaltered lacritin along with two controls, bovine serum albumin (BSA) and lysozyme.
Supplementary MaterialsSupplementary data 1 mmc1. acids that become pH sensors. Since the membrane fusion event happens in the pH range of 5C6, the most likely residues to function as pH detectors are histidines, aspartates and/or glutamates, which possess pKa in the appropriate pH range (Zhou et al., 2014). Based on a number of studies, multiple pH detectors are involved. First, from biochemical, x-ray, EM and virological studies, HA is known to undergo multiple reversible conformational changes when exposed to low pH (Xu and Wilson, 2011, Fontana et al., 2012, Leikina et al., 2002). Second, despite a high degree of structural homology within HA subtypes, examination of HA sequences does not reveal totally conserved titratable residues (Zhou et al., 2014, Mair et al., 2014). Third, membrane fusion happens at different pH ideals for different HA subtypes (Scholtissek, 1985, Puri et al., 1990, Korte et Rabbit Polyclonal to VAV3 (phospho-Tyr173) al., 2007). Fourth, mutagenesis studies possess ...
Molecular recognition via noncovalent interactions plays a key role in many biological processes such as antigen-antibody interactions, protein folding, the bonding and catalytic transformation of substrates by enzymes, etc. Amongst these noncovalent interactions, electrostatic interactions, hydrogen bonding, π-π interactions, and metal-to-ligand bonding are the most prominent. Exploring noncovalent interactions in host-guest systems that range from small hydrocarbon systems to more complex systems is the main motivation of this thesis. The present study involves the design, synthesis and characterization of clip-shaped molecules as host structures, and an examination of their binding properties with a variety of guests using NMR spectroscopy.. Several clips with a hydrocarbon or glycoluril backbone were synthesized. The binding of cations to small, hydrocarbon-based clips suggests that binding is enhanced by the rigidity and cooperativity between the two sidewalls of the clip. Binding is also ...
Protein NMR is the method of choice for determining protein structures at the atomic level in solution. In addition, NMR experiments allow characterization of protein dynamics at a wide range of time scales [1-7]. Dynamical studies of the past decade led to the emerging paradigm that the so-called native structure of a protein can be better viewed as a number of more or less similar conformers interconverting on different time scales. Functional interactions perturb this state by shifting the equilibrium towards active conformations that are present but are low-populated in the apo state. The most extreme examples of this kind of behavior are provided by intrinsically disordered proteins (IDPs) that adopt a plethora of diverse conformations in their free state but, at least some of them, might become fully or partially well ordered upon partner molecule binding [8, 9].. IDPs can not be described with single-conformer models but only with conformational ensembles capturing the diversity of ...
The discovery of dilute liquid crystalline media to align biological macromolecules has opened many new possibilities to study protein and nucleic acid structures by NMR spectroscopy. We inspect the basic alignment phenomenon for an ensemble of protein conformations to deduce relative contributions of each member to the residual dipolar coupling signals. We find that molecular fluctuations can affect the alignment and discover a resulting emphasis of certain conformations. However, the internal fluctuations are largely uncorrelated with those of the alignment, implying that proteins have liquidlike molecular surfaces. Furthermore, we consider the implications of a dynamic bias to structure determination using data from the weak alignment method ...
O:13:\PanistOpenUrl\:36:{s:10:\\u0000*\u0000openUrl\;N;s:6:\\u0000*\u0000idc\;N;s:6:\\u0000*\u0000fmt\;s:7:\journal\;s:6:\\u0000*\u0000doi\;s:0:\\;s:6:\\u0000*\u0000pii\;s:0:\\;s:7:\\u0000*\u0000pmid\;s:0:\\;s:9:\\u0000*\u0000atitle\;s:92:\CIRCULAR DICHROISM STUDIES OF CYANATE-INDUCED CONFORMATIONAL CHANGES IN HEMOGLOBINS A AND S.\;s:9:\\u0000*\u0000jtitle\;s:0:\\;s:9:\\u0000*\u0000stitle\;s:0:\\;s:7:\\u0000*\u0000date\;s:4:\1976\;s:9:\\u0000*\u0000volume\;s:0:\\;s:8:\\u0000*\u0000issue\;s:0:\\;s:8:\\u0000*\u0000spage\;s:0:\\;s:8:\\u0000*\u0000epage\;s:0:\\;s:8:\\u0000*\u0000pages\;s:0:\\;s:7:\\u0000*\u0000issn\;s:0:\\;s:8:\\u0000*\u0000eissn\;s:0:\\;s:9:\\u0000*\u0000aulast\;s:6:\SIMONS\;s:10:\\u0000*\u0000aufirst\;s:2:\ER\;s:9:\\u0000*\u0000auinit\;N;s:10:\\u0000*\u0000auinitm\;N;s:5:\\u0000*\u0000au\;a:4:{i:0;s:9:\SIMONS ER\;i:1;s:11:\HARTZBAND P\;i:2;s:8:\WHITIN J\;i:3;s:9:\CHAPMAN ...
In eukaryotic cells, proteins are translocated across the ER membrane through a continuous ribosome-translocon channel. It is unclear to what extent proteins can fold already within the ribosome-translocon channel, and previous studies suggest that only a limited degree of folding (such as the formation of isolated α-helices) may be possible within the ribosome. We have previously shown that the conformation of nascent polypeptide chains in transit through the ribosome-translocon complex can be probed by measuring the number of residues required to span the distance between the ribosomal P-site and the lumenally disposed active site of the oligosaccharyl transferase enzyme (J. Biol. Chem 271: 6241-6244).Using this approach, we now show that model segments composed of residues with strong helix-forming properties in water (Ala, Leu) have a more compact conformation in the ribosome-translocon channel than model segments composed of residues with weak helix-forming potential (Val, Pro). The main
Background. In eukaryotic cells, proteins are translocated across the ER membrane through a continuous ribosome-translocon channel. It is unclear to what extent proteins can fold already within the ribosome-translocon channel, and previous studies suggest that only a limited degree of folding (such as the formation of isolated α-helices) may be possible within the ribosome.. Results. We have previously shown that the conformation of nascent polypeptide chains in transit through the ribosome-translocon complex can be probed by measuring the number of residues required to span the distance between the ribosomal P-site and the lumenally disposed active site of the oligosaccharyl transferase enzyme (J. Biol. Chem 271: 6241-6244).Using this approach, we now show that model segments composed of residues with strong helix-forming properties in water (Ala, Leu) have a more compact conformation in the ribosome-translocon channel than model segments composed of residues with weak helix-forming potential ...
Serpins use an extraordinary mechanism of protease inhibition that depends on a rapid and marked conformational change and causes destruction of the covalently linked protease. Serpins thus provide stoichiometric, irreversible inhibition, and their dependence on conformational change is exploited fo …
Link for Professor Gonzalez. Abstract: Over the past two decades, stunning breakthroughs in the field of structural biology have continued to produce groundbreaking high-resolution structures of large, multi-component biomolecular machines. Comparative analyses of these static structures reveals the remarkable conformational flexibility of these machines and hints at the significant structural rearrangements that evidently accompany their functional cycles. Unfortunately, the experimental observation and characterization of these conformational dynamics is severely impeded by the size and complexity of biomolecular machines, severely limiting our understanding of the contributions that dynamics make to their functions. Using a combination of molecular genetic-, biochemical-, and single-molecule biophysical approaches, my research group aims to overcome these challenges and elucidate the precise roles that the conformational dynamics of biomolecular machines play in driving and controlling their ...
The coil to globule transition is a fundamental phenomenon in the physics of macro-molecules by reason of the multiplicity of arrangements of their conformation. Such conformational freedom is the main source of entropy in the molecule and is the main opponent to the transition towards the compact state, since a system tends to the state of maximum entropy. This phenomenon is captured by very simple models, such as the ensemble of Interacting Self avoiding Walks on the lattice. This model shows that the coil to globule transition belongs to the universality class of continuous transition called Θ point. Starting from a critical inspection of the definition of the interacting walks model, we introduce a refinement aiming to represent more precisely the entropy sourced from the local fluctuations of the molecule around its equilibrium conformations; this contribution is absent in the standard model which includes only the entropy generated by the multiplicity of the global conformations. Through ...
Some residues of the C, G, and H helices of Hb are a part of the α1β1 contact area. Most of these contacts are weak, non-covalent bonds, such as Van der Waals interactions and hydrogen bonds, although the latter have a less prominent role in α1β1 contact. These contacts form a rigid dimer, so that during Hb oxygenation and deoxygenation, movement in this area is extremely limited [1]. Therefore, any constitutional variation could give rise to structural modifications that can cause Hb precipitation in erythropoietic progenitors depending on the location of the residue within the helix, its participation in Hb functionality, and the characteristics of the residue. This, in turn, may cause ineffective erythropoiesis or hemolytic anemia. An example of these behaviors is Hb variants at position G19. Position 19 of the G helix of the globin β chain is occupied by residue 118, a histidine. This residue is located externally in the three-dimensional protein structure and interacts with two ...
Understanding the 3D molecular structure of proteins is of enormous importance in science, medicine and biotechnology. When determining the 3D structure of a protein using biophysical methods, it is often assumed that a protein molecule has a single, specific shape. Yet in reality, many proteins adopt a number of radically different conformations, that can interchange dynamically. Such a set of conformations is called an ensemble. It is precisely the ensemble aspect of protein structure that plays a major role in important diseases such as Parkinsons, type II diabetes or Alzheimers. Currently, there are few methods that can handle such ensembles, and the available methods are suboptimal, ad hoc and heuristic.. We have developed a statistically rigorous and computationally efficient method to determine the structure of protein ensembles (Olsson et al., J. Magn. Reson., 2010; Olsson et al., PLoS ONE, 2013), based on previous methods developed at the Bioinformatics center, targeting both NMR and ...
The investigation suggested that coronaviruses use conformational masking and glycan shielding to limit recognition by the immune response of infected hosts. Similarly to SARS-CoV S and MERS-CoV, the investigation found that the SARS-CoV-2 S trimer exists in multiple, distinct conformational states resulting from SB opening at the trimer apex. These structural changes are necessary…
List of protein structure prediction software Chou PY, Fasman GD (1974). "Prediction of protein conformation". Biochemistry. 13 ... Chou PY, Fasman GD (1978). "Empirical predictions of protein conformation". Annu Rev Biochem. 47: 251-276. doi:10.1146/annurev. ... doi:10.1093/protein/11.5.345. PMID 9681866. Chen H, Gu F, Huang Z (2006). "Improved Chou-Fasman method for protein secondary ... Kyngas J, Valjakka J (1998). "Unreliability of the Chou-Fasman parameters in predicting protein secondary structure". Protein ...
Ramachandran, G.N.; Sasiskharan, V. (1968). "Conformation of polypeptides and proteins". Advances in Protein Chemistry. 23: 283 ... Hovmöller, S.; Zhou, T.; Ohlson, T. (2002). "Conformations of amino acids in proteins". Acta Crystallographica D. 58 (Pt 5): ... Richardson, J.S. (1981). "Anatomy and Taxonomy of Protein Structures". Advances in Protein Chemistry. 34: 167-339. doi:10.1016/ ... Richardson, J.S. (1981). "Anatomy and Taxonomy of Protein Structures". Advances in Protein Chemistry. 34: 167-339. doi:10.1016/ ...
"Conformation of polypeptides and proteins". Advances in Protein Chemistry Volume 23. Advances in Protein Chemistry. 23. pp. 283 ... such as protein-protein interactions (PPI), protein-peptide interactions, protein-ligand interactions (PLI), and protein-DNA ... ProtCID: The Protein Common Interface Database Database of similar protein-protein interfaces in crystal structures of ... protein threading, de novo protein structure prediction, and secondary structure prediction is available in the list of protein ...
Ramachandran, G. N.; Sasisekharan, V. (1968). "Conformation of polypeptides and proteins". Advances in Protein Chemistry. 23: ... While the majority of the Peptide bonds within proteins exist in trans (planar) conformation because of the partial double-bond ... step in the process of protein folding. Immunophilins, with their prolyl isomerase activity, thus function as protein-folding ... FK506 binds with high affinity to other smaller proteins, such as FKBP-12. FKBP-12 and cyclophilins both share common peptide- ...
Studies of protein conformation (DPhil thesis). University of Oxford. CS1 maint: discouraged parameter (link) http://www3. ... Sternberg's research interests are in protein structure prediction, protein function prediction, prediction of macromolecular ... Protein Engineering: a practical approach and Protein Structure Prediction: a practical approach. During his DPhil research at ... Zvelebil, M. J.; Barton, G. J.; Taylor, W. R.; Sternberg, M. J. (1987). "Prediction of protein secondary structure and active ...
Celada, F.; Schumaker, V.N.; Sercarz, E.E. (2012). Protein Conformation as an Immunological Signal. Springer US. p. 240. ISBN ...
Levitt, M. (1976). "A simplified representation of protein conformations for rapid simulation of protein folding". Journal of ... Michael Levitt publications indexed by Google Scholar Levitt, Michael (1972). Conformation analysis of proteins (PhD thesis). ... He has also worked on simplified representations of protein structure for analysing folding and packing, as well as developing ... Xia, Y.; Huang, E. S.; Levitt, M.; Samudrala, R. (2000). "Ab initio construction of protein tertiary structures using a ...
Sternberg, Michael Joseph Ezra (1977). Studies of protein conformation (DPhil thesis). University of Oxford. Phillips, D. C.; ...
Sibanda, BL; Blundell TL; Thornton JM (1989). "Conformation of β-hairpins in protein structures. A systematic classification ... Leader, DP; Milner-White EJ (2009). "Motivated Proteins: A web application for studying small three-dimensional protein motifs ... Chan, EAW; Hutchinson EG (1993). "Identification, classification and analysis of β-bulges in proteins". Protein Science. 2 (10 ... Two websites are available for finding and examining β bulge loops in proteins, Motivated Proteins: [1] and PDBeMotif: [2]. ...
Sibanda, B. L.; Blundell, T. L.; Thornton, J. M. (1989). "Conformation of beta-hairpins in protein structures. A systematic ... Thornton, J. M.; Singh, J; Campbell, S; Blundell, T. L. (1988). "Protein-protein recognition via side-chain interactions". ... "The Protein Feature Ontology: A tool for the unification of protein feature annotations". Bioinformatics. 24 (23): 2767-2772. ... for evaluating the quality of experimentally defined protein structures: this is used widely to check protein structures. She ...
"An analysis of side-chain conformation in proteins". International Journal of Peptide and Protein Research. 13 (2): 170-84. doi ... Banerjee, R.; Das, K.; Ravishankar, R.; Suguna, K.; Surolia, A.; Vijayan, M. (7 June 1996). "Conformation, protein-carbohydrate ... side chain conformation in proteins and additional binding sites in lysozyme. Vijayan has published more than 260 peer reviewed ... "Snapshots of RecA protein involving movement of the C-domain and different conformations of the DNA-binding loops: ...
"Roles of electrostatics and conformation in protein-crystal interactions". PLOS ONE. 5 (2): e9330. Bibcode:2010PLoSO...5.9330A ... Osteopontin is an extracellular structural protein and therefore an organic component of bone. Synonyms for this protein ... "Cooperative Unfolding of Compact Conformations of the Intrinsically Disordered Protein Osteopontin". Biochemistry. 52 (31): ... which are attached to the protein during post-translational modification in the Golgi apparatus. The protein is rich in acidic ...
Glycolipid transfer protein is a protein that in humans is encoded by the GLTP gene. The protein encoded by this gene is ... probing conformation using fluorescence spectroscopy". Biochemistry. 43 (31): 10285-94. doi:10.1021/bi0495432. PMC 2593833. ... "Entrez Gene: GLTP glycolipid transfer protein". Brown RE, Mattjus P (2007). "Glycolipid transfer proteins". Biochim. Biophys. ... 2004). "Glycolipid transfer protein mediated transfer of glycosphingolipids between membranes: a model for action based on ...
During illumination with light, these proteins change their conformation. In the process they gain or lose their ability to ... Some fluorescent proteins can be switched on and off by light of an appropriate wavelength. They can be used in a RESOLFT-type ... Just as with proteins, also some organic dyes can change their structure upon illumination. The ability to fluoresce of such ... Inducing conformational changes in proteins can be achieved already at much lower switching light intensities as compared to ...
Janin, J.; Wodak, S. (1978). "Conformation of amino acid side-chains in proteins*1". Journal of Molecular Biology. 125 (3): 357 ... In biochemistry, a Janin plot, like a Ramachandran plot, is a way to visualize dihedral angle distributions in protein ...
Durussel I, Rhyner JA, Strehler EE, Cox JA (1993). "Cation binding and conformation of human calmodulin-like protein". ... Calmodulin-like protein 3 is a protein that in humans is encoded by the CALML3 gene. GRCh38: Ensembl release 89: ... Rogers MS, Kobayashi T, Pittelkow MR, Strehler EE (2001). "Human calmodulin-like protein is an epithelial-specific protein ... 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173-8. doi:10.1038 ...
Method of modifying the conformation of food and feed proteins. US Patent. G Szabolcsi, 1991. Enzimes Analizis. Akadémiai Kiadó ...
"Lysine Acetylation Controls Local Protein Conformation by Influencing Proline Isomerization". Molecular Cell. 55 (5): 733-744. ... a process that can lock proteins in a nonnative structure that can affect render the protein temporarily ineffective. Although ... Without the cis conformation of the pSer5-Pro6 bond, created by Ess1/Pin1, Nrd1 cannot bind to RNAP II. Any variation from this ... The protein p53, along with p63 and p73, are responsible for ensuring that alterations to the genome are corrected and for ...
"Ubiquitin chain conformation regulates recognition and activity of interacting proteins". Nature. 492 (7428): 266-70. Bibcode: ... "A human protein-protein interaction network: a resource for annotating the proteome". Cell. 122 (6): 957-68. doi:10.1016/j.cell ... Polyubiquitin-C is a protein encoded by the UBC gene in humans. Polyubiquitin-C is one of the sources of ubiquitin, along with ... Chen L, Dong W, Zou T, Ouyang L, He G, Liu Y, Qi Y (August 2008). "Protein phosphatase 4 negatively regulates LPS cascade by ...
Prediction of Protein Structures and the Principles of Protein Conformation. New York: Plenum. pp. 599-623. ISBN 0-306-43131-9 ... Alanine (symbol Ala or A) is an α-amino acid that is used in the biosynthesis of proteins. It contains an amine group and a ... It is a catabolic pathway, and relies upon protein breakdown in the muscle tissue. Whether and to what extent it occurs in non- ... In this model the selection of monomers (i.e. amino acids) for ribosomal protein synthesis is rather limited to those Alanine ...
β-Sheets predominate as the secondary level of protein conformation. The structure of trans-sialidase includes a catalytic beta ... There are two major proteins on the surface of influenza virus particles. One is the lectin haemagglutinin protein with three ... The first step involves the distortion of the α-sialoside from a 2C5 chair conformation (the lowest-energy form in solution) to ... which allow for secretion of FLAG-tagged proteins and further purification. The enzymatic mechanism of influenza virus ...
Sibanda, B.L.; Blundell, T.L.; Thorton, J.M. (1985). "Conformations of Beta-Hairpins in Protein Structures". Nature(London) 316 ... To see this clearly, the Pin1 Domain protein is shown to the left as an example. Proteins that are β-sheet rich, also called WW ... function by adhering to proline-rich and/or phosphorylated peptides to mediate protein-protein interactions. The "WW" refers to ... have used protein NMR to show that beta-hairpins can be formed from isolated short peptides in aqueous solution, suggesting ...
Chou, Peter Y.; Fasman, Gerald D. (1974-01-15). "Prediction of protein conformation". Biochemistry. 13 (2): 222-245. doi: ... "Protein BLAST: search protein databases using a protein query". Retrieved 2018-05-04. EMBL-EBI. " ... "uncharacterized protein C21orf58 isoform 1 [Homo sapiens] - Protein - NCBI". Retrieved 2018-02-04. "C21orf58 ... "KLHL20 - Kelch-like protein 20 - Homo sapiens (Human) - KLHL20 gene & protein". Retrieved 2018-05-06. "TimeTree ...
"Shockley-Ramo theorem measures conformation changes of ion channels and proteins". Journal of Computational Electronics. 6 (1-3 ... including semiconductor radiation detection and calculations of charge movement in proteins. Shockley, W. (1938). "Currents to ...
The protein adopts a broken-helical conformation on lipoprotein particles while it forms an extended helical structure on lipid ... McLean PJ, Kawamata H, Ribich S, Hyman BT (March 2000). "Membrane association and protein conformation of alpha-synuclein in ... Alpha-synuclein is a protein that, in humans, is encoded by the SNCA gene. Alpha-synuclein is a neuronal protein that regulates ... The majority form of the protein, and the one most investigated, is the full-length protein of 140 amino acids. Other isoforms ...
However, only half of the protein has a defined secondary conformation. The rest of this protein is intrinsically disordered. ... This protein has a length of 421 amino acids, among which, we have to highlight the Glutamine number 58 (Gln or Q), which is ... ATAT1 it is not a modular protein because it only have one domain localized from the first amino acid to the one hundred and ... The protein's active site contains several conserved residues that could potentially function as general bases in the reaction ...
Hamelryck T, Kent JT, Krogh A (2006). "Sampling Realistic Protein Conformations Using Local Structural Bias". PLOS Comput. Biol ... Applications to protein modeling". J. Mol. Biol. 235 (5): 1501-31. doi:10.1006/jmbi.1994.1104. PMID 8107089. Krogh A, Mian IS, ... Krogh A, Larsson B, von Heijne G, Sonnhammer EL (2001). "Predicting transmembrane protein topology with a hidden Markov model: ... Winther O, Krogh A (2004). "Teaching computers to fold proteins". Phys. Rev. E. 70 (3): 030903. arXiv:cond-mat/0309497. Bibcode ...
Kelly JW (February 1996). "Alternative conformations of amyloidogenic proteins govern their behavior". Curr. Opin. Struct. Biol ... These proteins include: transthyretin (ATTR, the most commonly implicated protein), apolipoprotein A1, and gelsolin. Due to the ... Ghoshdastider U, Popp D, Burtnick LD, Robinson RC (2013). "The expanding superfamily of gelsolin homology domain proteins". ... The aggregation of one precursor protein leads to peripheral neuropathy and/or autonomic nervous system dysfunction. ...
... is a signal transducing protein; thus, the balance between conformations regulates protein activity. ADK has a ... shows the conformations of ADK when binding with ATP or AMP. The study shows that there are three relevant conformations or ... conformations amongst those that are sampled by ADK. These 'closed' conformations are hypothesized to help with removal of ... Sub-cellular localization of the ADK enzymes is done by including a targeting sequence in the protein. Each isoform also has ...
"The conformation of neurotensin bound to its G protein-coupled receptor" (PDF). Proceedings of the National Academy of Sciences ... He has used the technology amongst others to study the behavior of bacterial proteins, protein aggregation in Alzheimer's and ... for the analysis of membrane embedded proteins such as G-protein coupled receptors and ion channels and for the ... his attention has been focussed on the analysis of in-cell NMR to study the structure and function of proteins in their native ...
Sedimentation Velocity Analysis of Heterogeneous Protein-Protein Interactions: Lamm Equation Modeling and Sedimentation ... and conformation. Samples are centrifuged with a high-density solution such as sucrose, caesium chloride, or iodixanol. The ... By 1900, it had been generally accepted that proteins were composed of amino acids; however, whether proteins were colloids or ... Howlett, G.J., Minton, A.P., Rivas, G. Analytical Ultracentrifugation for the Study of Protein Association and Assembly. ...
ER Translocon complex.[2] Many protein complexes are involved in protein synthesis. The actual production takes place in the ... Move these two large substrates into their proper locations and conformations.. *Activate the Asn amide nitrogen atom for the ... Sec61 is the protein-conducting channel and the OST adds sugar moieties to the nascent protein. ... Oligosaccharyltransferase or OST (EC is a membrane protein complex that transfers a 14-sugar oligosaccharide from ...
The balance between potassium and sodium is maintained by ion transporter proteins in the cell membrane.[231] The cell membrane ... The heavier alkali metals also favour the sterically congested conformation.[142] Several crystal structures of organopotassium ...
The term alpha-1 refers to the protein's behavior on protein electrophoresis. On electrophoresis, the protein component of the ... Elliott PR, Abrahams JP, Lomas DA (January 1998). "Wild-type alpha 1-antitrypsin is in the canonical inhibitory conformation". ... which could confer this protein particular protein-cell recognition properties. The single cysteine residue of A1AT in position ... As protein electrophoresis is imprecise, the A1AT phenotype is analysed by isoelectric focusing (IEF) in the pH range 4.5-5.5, ...
Fig 2. Schematic diagram of a GABAA receptor protein ((α1)2(β2)2(γ2)) which illustrates the five combined subunits that form ... weak modulators of GABAA receptor function because the flexible side chains in these analogues do not have the conformations ... The synaptic anchoring protein Gephyrin is indirectly linked to the GABAA receptors. ... molecules that increase the activity of the GABAA receptor protein in the vertebrate central nervous system. ...
Receptor binding, as well as membrane fusion, are catalyzed by the protein E, which changes its conformation at low pH, causing ... and forms a complex with protein E. The immature particles are processed in the Golgi apparatus by the host protein furin, ... At first, an immature form of the virus particle is produced inside the ER, whose M-protein is not yet cleaved to its mature ... Host proteases cut this polyprotein into three structural (C, prM, E) and seven nonstructural proteins (NS1, NS2A, NS2B, NS3, ...
This process increases transcription of certain genes, notably CYP1A1, followed by increased CYP1A1 protein production.[28] ... Absolute configuration and conformation". Proceedings of the National Academy of Sciences. Retrieved January 3, 2006.. ... "Basal and inducible CYP1 mRNA quantitation and protein localization throughout the mouse gastrointestinal tract". Free Radic ...
In addition, these side-chains can be attached to other types of molecules, like proteins, as in polysaccharide-K. ...
... who believed that transcription was activated by protein-DNA and protein-protein interactions on largely naked DNA templates, ... The most basic such formation is the 10 nm fiber or beads on a string conformation. This involves the wrapping of DNA around ... Nuclear protein Ataxia-Telangiectasia (NPAT), also known as nuclear protein coactivator of histone transcription, is a ... The first step of chromatin structure duplication is the synthesis of histone proteins: H1, H2A, H2B, H3, H4. These proteins ...
This bacterial protein complex is a machine for folding other proteins, which get trapped within the shell. Fatty acid synthase ... However, a micrograph often contains particles in multiple different orientations and/or conformations, and so to get more ... Proteins in vitreous ice usually adopt a random distribution of orientations (or viewing angles), allowing a fairly isotropic ... Important information on protein synthesis, ligand binding and RNA interaction can be obtained using this novel technique at ...
NMR is also useful for probing the binding of nucleic acid molecules to other molecules, such as proteins or drugs. This can be ... and sugar pucker conformations. The presence or absence of imino proton resonances, or of coupling between 15N atoms across a ... Nucleic acid NMR uses techniques similar to those of protein NMR, but has several differences. Nucleic acids have a smaller ... Nucleic acids also tend to have resonances distributed over a smaller range than proteins, making the spectra potentially more ...
Ligands connect to specific receptor proteins based on the shape of the active site of the protein. ... Change in the receptor conformation such that binding of the agonist does not activate the receptor. This is seen with ion ... and can be a protein or peptide (short protein), or another small molecule such as a neurotransmitter, hormone, pharmaceutical ... In biochemistry and pharmacology, a receptor is a protein molecule that receives chemical signals from outside a cell.[1] When ...
"for their studies of the structures of globular proteins"[۲۵] ۱۹۷۲ ویلیام اشتین[۱] United States "for his work on ribonuclease ... especially concerning the connection between the amino acid sequence and the biologically active conformation"[۲۶] ... "for their discovery of جی پروتئینs and the role of these proteins in ورارسانی پیام in cells"[۷۳] ... "for their interpretation of the رمز ژنتیکی and its function in protein synthesis"[۵۷] ...
I. Isolation and characterization of the protein-glycogen complex". Journal of Biological Chemistry. 245 (24): 6642-6648. PMID ... There is also an alternative proposed mechanism involving a positively charged oxygen in a half-chair conformation.[3] ... First, the catalytic sites are relatively buried, 15Å from the surface of the protein and from the subunit interface.[6] This ... The glycogen phosphorylase monomer is a large protein, composed of 842 amino acids with a mass of 97.434 kDa in muscle cells. ...
Fractionation of proteins by heparin chromatography։ Methods Mol Biol։ Methods in Molecular Biology™ 424։ 2008։ էջեր 213-21։ ... N.M.R. and molecular-modelling studies of the solution conformation of heparin»։ Biochem. J. 293 (Pt 3): 849-858։ հունվարի 1, ... B. Mulloy, M.J. Forster։ «N.M.R. and molecular-modeling studies of the solution conformation of heparin» ... Gatti G., Casu B., Hamer G. K., Perlin A. S. (1979)։ «Studies on the Conformation of Heparin by1H and13C NMR Spectroscopy»։ ...
The hydroxyl group also forces the ribose into the C3'-endo sugar conformation unlike the C2'-endo conformation of the ... DNA and proteins seemed the dominant macromolecules in the living cell, with RNA only aiding in creating proteins from the DNA ... where a nucleotide-based molecule is needed to synthesize protein, and a peptide-based (protein) molecule is needed to make ... The ability to catalyse the formation of peptide bonds between amino acids to produce short peptides or longer proteins. This ...
The protein degradation processEdit. Ribbon diagram of ubiquitin, the highly conserved protein that serves as a molecular tag ... Three distinct conformational states of the 26S proteasome.[37] The conformations are hypothesized to be responsible for ... Proteasomes are protein complexes which degrade unneeded or damaged proteins by proteolysis, a chemical reaction that breaks ... Proteins are tagged for degradation with a small protein called ubiquitin. The tagging reaction is catalyzed by enzymes called ...
This leads to antiviral protein production, such as protein kinase R, which inhibits viral protein synthesis, or the 2′,5′- ... When the cytoplasmic receptors MDA5 and RIG-I recognize a virus the conformation between the caspase-recruitment domain (CARD) ... "Resistance" (R) proteins, encoded by R genes, are widely present in plants and detect pathogens. These proteins contain domains ... The cascade is composed of many plasma proteins, synthesized in the liver, primarily by hepatocytes. The proteins work together ...
"The Alzheimer's Disease-Associated Amyloid β-Protein Is an Antimicrobial Peptide". PLoS ONE 5 (3): e9505. Bibcode:2010PLoSO... ... "The Alzheimer's peptides Abeta40 and 42 adopt distinct conformations in water: a combined MD / NMR study". J. Mol. Biol. 368 ... Shinkai Y, Yoshimura M, Ito Y, Odaka A, Suzuki N, Yanagisawa K, Ihara Y (September 1995). "Amyloid beta-proteins 1-40 and 1-42( ... Zou K, Gong JS, Yanagisawa K, Michikawa M (June 2002). "A novel function of monomeric amyloid beta-protein serving as an ...
Immunoglobulin-binding protein - Proteins such as protein A, protein G, and protein L that are capable of binding to antibodies ... Antigen specificity is due primarily to the side-chain conformations of the antigen. It is measurable and need not be linear or ... An autoantigen is usually a normal protein or protein complex (and sometimes DNA or RNA) that is recognized by the immune ... Lipids and nucleic acids are antigenic only when combined with proteins and polysaccharides.[citation needed] Non-microbial non ...
In the absence of CDC42 and PIP2, N-WASp is in an inactive, locked conformation.[9] Cooperative binding of both CDC42 and PIP2 ... protein binding. • identical protein binding. • actin binding. • protein kinase binding. • small GTPase binding. • Rac GTPase ... "The Wiskott-Aldrich syndrome protein-interacting protein (WIP) binds to the adaptor protein Nck". The Journal of Biological ... The Wiskott-Aldrich Syndrome protein (WASp) is a 502-amino acid protein expressed in cells of the hematopoietic system. In the ...
"Cellular prion protein conformation and function". Proc. Natl. Acad. Sci. U.S.A. 108 (42): 17308-13. Bibcode:2011PNAS.. ... ATP-dependent protein binding. • metal ion binding. • tubulin binding. • protein binding. • identical protein binding. • copper ... PRNP (prion protein) is the human gene encoding for the major prion protein PrP (proetase-resistant-protein, Pr for prion, and ... negative regulation of protein processing. • protein destabilization. • activation of protein kinase activity. • calcium- ...
"for their contributions to the development of the concept of conformation and its application in chemistry"[61] ... "for their preparation of enzymes and virus proteins in a pure form"[38] ... "for his work on the structure of proteins, especially that of insulin"[50] ... "for the discovery and development of the green fluorescent protein, GFP"[101] ...
IgE that can specifically recognise an allergen (typically this is a protein, such as dust mite Der p 1, cat Fel d 1, grass or ... "The crystal structure of IgE Fc reveals an asymmetrically bent conformation". Nat. Immunol. 3 (7): 681-6. doi:10.1038/ni811. ...
Pabo C, Sauer R (1984). "Protein-DNA recognition". Annu Rev Biochem 53: 293-321. doi:10.1146/ ... "Single-stranded adenine-rich DNA and RNA retain structural characteristics of their respective double-stranded conformations ...
Contributions of protein-protein and protein-membrane interactions toward complex formation". The Journal of Biological ... Factor Xa inhibitors generally bind in an L-shaped conformation, where one group of the ligand occupies the anionic S1 pocket ... The affinity of this protein for factor Xa is increased 1000-fold by the presence of protein Z, while it does not require ... protein binding. • serine-type peptidase activity. • serine-type endopeptidase activity. • phospholipid binding. • hydrolase ...
The shape into which a protein naturally folds is known as its native conformation.[20] Although many proteins can fold ... Main article: Protein domain. Many proteins are composed of several protein domains, i.e. segments of a protein that fold into ... globular proteins, fibrous proteins, and membrane proteins. Almost all globular proteins are soluble and many are enzymes. ... Protein purification. Main article: Protein purification. To perform in vitro analysis, a protein must be purified away from ...
The ACTH receptor is a seven-membrane-spanning G protein-coupled receptor.[7] Upon ligand binding, the receptor undergoes ... conformation changes that stimulate the enzyme adenylyl cyclase, which leads to an increase in intracellular cAMP[8] and ... and their associated electron transfer proteins.[8] This effect is observed over several hours.[8] ... subsequent activation of protein kinase A. ACTH influences steroid hormone secretion by both rapid short-term mechanisms that ...
This is how the protein checks for the recognition site as it allows the DNA duplex to follow the shape of the protein. In ... the repressor changes conformation and falls off the operator. RNAP is then able to bind to the promoter and begin ... The lacI gene synthesizes LacI repressor protein. The LacI repressor protein represses lacZYA by binding to the operator ... lacZYA transcribes the proteins needed for lactose breakdown.[1] lacI synthesizes the repressor of the lacZYA gene.[1] The gene ...
"for their contributions to the development of the concept of conformation and its application in chemistry"[68] ... "for their preparation of enzymes and virus proteins in a pure form"[45] ... "for his work on the structure of proteins, especially that of insulin"[57] ... especially concerning the connection between the amino acid sequence and the biologically active conformation"[71] ...
Derek J. Chadwick and Kate Widdows are editors for Protein Conformation and other scientific titles. ... protein engineering and molecular modeling offer provocative insights into current views on the protein folding problem and ... Comparative Analysis of Protein Three-Dimensional Structures and an Approach to the Inverse Folding Problem (T. Blundell). ... How the amino acid sequence of a protein determines its three-dimensional structure is a major problem in biology and chemistry ...
The study of protein stability is currently undergoing a dramatic change. Early work, especially after Kauzmann (1959), ... In: Fasman G.D. (eds) Prediction of Protein Structure and the Principles of Protein Conformation. Springer, Boston, MA. * DOI ... Prediction of Protein Structure and the Principles of Protein Conformation pp 161-192 , Cite as ... Amino Acid Substitution Cross Link Protein Stability Stabilization Energy Protein Conformation These keywords were added by ...
Conformation of proteins in interfaces: Like many other substances with both hydrophilic and hydrophobic groups, soluble ... Proteins, when forming an interfacial film, are present as a monomolecular layer-i.e., a layer one molecule in height. Although ... Within the interface, proteins spread, forming thin films. Measurements of the surface tension, or interfacial tension, of such ... proteins tend to migrate into the interface between air and water or oil and water; the term oil here means a hydrophobic ...
Influence of proline residues on protein conformation.. MacArthur MW1, Thornton JM. ... an analysis has been made of all proline residues and their local conformations extracted from the Brookhaven Protein Data bank ... the influence of proline on the conformation of the preceding residue and the conformations of various proline patterns (Pro- ... We have considered the conformation of the proline itself, the relative occurrence of cis and trans peptides preceding proline ...
The Laboratory of Protein Conformation and Dynamics integrates complementary biophysical and biochemical techniques to ...
Regulation of protein kinases; controlling activity through activation segment conformation.. Nolen B1, Taylor S, Ghosh G. ... There are currently at least forty-six unique protein kinase crystal structures, twenty-four of which are available in an ... Here we examine these structures using a structural bioinformatics approach to understand how the conformation of the ...
Predicting the local structure of a protein in terms of protein blocks is the general objective of this work. A new approach, ... This form of analyzing proteins involves drafting its structure as a string of Protein Blocks. ... to scan this database and predict most probable backbone conformations for the protein local structures. Though PB-kPRED uses ... One such library, Protein Blocks, is composed of 16 standard 5-residues long structural prototypes. ...
Protein-bound conformation of a specific inhibitor against Candida albicans myristoyl-CoA:protein N-myristoyltransferase in the ...
IrisFP fluorescent protein in its green form, cis conformation. *DOI: 10.2210/pdb2VVH/pdb ... GREEN TO RED PHOTOCONVERTIBLE GPF-LIKE PROTEIN EOSFP. A, B, C, D. 226. Lobophyllia hemprichii. Mutation(s): 3 ... Like its parent protein EosFP, IrisFP also photoconverts irreversibly to a red-emitting state under violet light because of an ... Photoactivatable fluorescent proteins (FPs) are powerful fluorescent highlighters in live cell imaging and offer perspectives ...
... is a protein kinase that phosphorylates and activates several other protein kinases from the AGC group (which includes PKA, PKG ... Phosphoinositide-dependent protein kinase 1, a sensor of protein conformation Trends Biochem Sci. 2004 Mar;29(3):136-42. doi: ... Phosphoinositide-dependent protein kinase 1 (PDK1) is a protein kinase that phosphorylates and activates several other protein ... interact with and phosphorylate specific substrate conformations and thus sets PDK1 at the centre of a protein conformation ...
Significance of bound water to local chain conformations in protein crystals Message Subject (Your Name) has sent you a message ... Significance of bound water to local chain conformations in protein crystals. C H Robert and P S Ho ... The fractional water occupancy of each was found by comparison of the total number of conformations in the database regardless ... We examine how the polypeptide chain in protein crystal structures exploits the multivalent hydrogen-bonding potential of bound ...
Structure of the RSV F protein in the post-fusion conformation. *DOI: 10.2210/pdb3RRT/pdb ... Here, we present the 2.8-Å crystal structure of the trimeric RSV F ectodomain in its postfusion conformation. The structure ... Mechanistically, these results suggest that 101F and motavizumab can bind to multiple conformations of the fusion glycoprotein ... The structural preservation of neutralizing epitopes in the postfusion state suggests that this conformation can elicit ...
Neame, P. J. and Gallagher, J. T. (2005) Extracellular Matrix Heparan Sulfate Proteoglycans, in Amyloid Proteins: The Beta ... Sheet Conformation and Disease (ed J. D. Sipe), Wiley-VCH Verlag GmbH, Weinheim, Germany. doi: 10.1002/9783527619344.ch7 ...
2011) Bihelix: Towards de novo structure prediction of an ensemble of G-protein coupled receptor conformations. Proteins 80(2): ... the crystal conformation for each helix must be in that helixs top 36 conformations. The ranking of the crystal conformation ... We rely on energy ordering the final set of conformations without ligand or G protein and there could be too many nonactive ... SuperBiHelix method for predicting the pleiotropic ensemble of G-protein-coupled receptor conformations. Jenelle K. Bray, ...
... protein 3D conformation prediction at rest). PSP is defined as Protein Structure Prediction (protein 3D conformation prediction ... protein 3D conformation prediction at rest) abbreviated? PSP stands for Protein Structure Prediction ( ... PSP stands for Protein Structure Prediction (protein 3D conformation prediction at rest). ... Protein structure prediction, 2d ed. To that end, this reference sheds light on the methods used for protein structure ...
Research in my lab focuses on atomic-level mechanisms of protein regulation, protein-ligand interactions, and computer-aided ... I am interested in the structure, function, and evolution of proteins and their assemblies. As Associate Dean of Research, I ... DeGrado receives Protein Societys Stein and Moore Award. Wed Feb 11, 2015 ... The award is given annually by the international society "to recognize eminent leaders in protein science who have made ...
Table 3 Binding of secreted forms of RSV F protein to conformation-indicating antibodies following transfection of modified ... From: Modified mRNA/lipid nanoparticle-based vaccines expressing respiratory syncytial virus F protein variants are immunogenic ...
Protein-protein interaction analysis of the halobacterial Che proteins revealed that CheF1 directly interacts with CheY, CheD ... Protein concentration (mg ml−1). 10. 10. Buffer composition of protein solution. 20 mM Tris-HCl pH 7.5, 100 mM NaCl, 5 mM DTT. ... Proteins from H. salinarum have been expressed recombinantly in E. coli, but primarily as unfolded proteins that rely on the ... In both crystal forms, CheY is arranged in a domain-swapped conformation. CheF, the protein bridging the chemotaxis signal ...
... the myelin basic proteins and the proteolipid proteins (DM-20/PLP). The myelin basic proteins are extrinsic membrane proteins ... The proteolipid protein gene products DM-20 and PLP are adhesive intrinsic membrane proteins that make up ≥50% of the protein ... Curiously, changes in protein conformation imparted by the PLP-specific peptide not only confer sensitivity to amino acid ... Conservation of Topology, But Not Conformation, of the Proteolipid Proteins of the Myelin Sheath. Alexander Gow, Alexander ...
... protein conformations and protein-protein interactions. In addition, other complementary techniques will be used such as SPR, ... protein recognition and interaction by investigating intermediate protein active conformations (excited state), protein ... The project involves biochemistry in terms of protein expression, purification and establishing protein-protein interaction ... Postdoctoral Position: Intermediate Protein Active Conformations, Dynamics and Interactions Investigation Using NMR ...
Conformation Rules Part 3: News, Common Threads, Debate from San Diego Protein Misfolding Conference. Go to another part. ... Huntingtons Protein Snarls Axonal Traffic 2 Oct 2003. * Conformation Rules Part 1: News, Common Threads, Debate from San Diego ... Conformation Rules Part 2: News, Common Threads, Debate from San Diego Protein Misfolding Conference 17 Dec 2004. ... Conformation Rules Part 2: News, Common Threads, Debate from San Diego Protein Misfolding Conference 17 Dec 2004. ...
In this state, proteins show repeated substructures like alpha helices and beta sheet ... A protein is a linear chain of amino acids that folds into a unique functional structure, called its native state. ... Unger, I., Moult, J.: Finding the lowest free energy conformation of a protein is an NP-hard problem: Proof and implications. ... Patton, A., Punch, W., Goodman, E.: A Standard GA approach to native protein conformation prediction. In: Proceedings of the ...
An autoinhibitory conformation of the Bacillus subtilis spore coat protein SpoIVA prevents its premature ATP-independent ... An autoinhibitory conformation of the Bacillus subtilis spore coat protein SpoIVA prevents its premature ATP-independent ... Driks A, Roels S, Beall B, Moran CP Jr & Losick R (1994) Subcellular localization of proteins involved in the assembly of the ... Ramamurthi KS & Losick R (2008) ATP-driven self-assembly of a morphogenetic protein in Bacillus subtilis. Mol Cell 31: 406-414. ...
Characterizing conformation changes in proteins through the torsional elastic response. Authors: Dos Santos, Helena G.; Klett, ... The relationship between functional conformation changes and thermal dynamics of proteins is investigated with the help of the ... This article is part of a Special Issue entitled: The emerging dynamic view of proteins: Protein plasticity in allostery, ... than to pairs of conformations with the same ligands. This deep relationship between the thermal dynamics of a protein, ...
... and some proteins interacted specifically with the closed conformation. Most of the Merlin-proximal proteins were components of ... Proximity biotinylation identifies a set of conformation-specific interactions between Merlin and cell junction proteins ... Proximity biotinylation identifies a set of conformation-specific interactions between Merlin and cell junction proteins ... Proximity biotinylation identifies a set of conformation-specific interactions between Merlin and cell junction proteins ...
Identifying structural hotspots, understanding drug/protein or protein/protein interactions or determining the structural ... and enable biopharma researchers to gain greater insights into protein conformation and protein interactions more quickly, more ... The information and insights gained following data analysis using the HDExaminer software can be used to probe protein ... biopharmaceutical characterization requires deeper understanding of the conformational structure of biotherapeutic proteins, ...
In an example application we modeled the process of complex assembly between two proteins: Troponin C (TnC) and the N-terminal ... This way our procedure opens up a new possibility for studying mechanisms of protein complex assembly, which may be a ... CABS-dock is a versatile and efficient tool for modeling the structure, dynamics and interactions of protein complexes. The ... a phenomenon that can be modeled only when protein flexibility is properly accounted for. ...
Blocking cytoplasmic protein synthesis with cycloheximide had no effect on the biphasic change in Y10B labeling of afferent- ... During this second phase, NM neurons putatively destined to die, based on their failure to synthesize protein, are unlabeled by ... Six hours following afferent deprivation, dying NM neurons demonstrate complete loss of ribosomes and cessation of protein ... A biphasic change in ribosomal conformation during transneuronal degeneration is altered by inhibition of mitochondrial, but ...
The role of RNA conformation in RNA-protein recognition. ... Advances and Challenges in Protein-RNA: Recognition, Regulation ... The role of RNA conformation in RNA-protein recognition. Yael Mandel-Gutfreund, Video: The role of RNA conformation in RNA- ... Yael Mandel-Gutfreund, The role of RNA conformation in RNA-protein recognition, Advances and Challenges in Protein-RNA: ... Yael Mandel-Gutfreund, Video: The role of RNA conformation in RNA-protein recognition ...
Inverse Agonists: Tools to Reveal Ligand-Specific Conformations of G Protein-Coupled Receptors ... Inverse Agonists: Tools to Reveal Ligand-Specific Conformations of G Protein-Coupled Receptors ... Inverse Agonists: Tools to Reveal Ligand-Specific Conformations of G Protein-Coupled Receptors ... Inverse Agonists: Tools to Reveal Ligand-Specific Conformations of G Protein-Coupled Receptors ...
  • Background: Although methods based on highly abstract descriptions of protein structures, such as VAST and TOPS, can perform very fast protein structure comparison, the results can lack a high degree of biological significance. (
  • abstract = "This study reports on the preparation of riboflavin-loaded whey protein isolate (WPI) microparticles, using desolvation and then spray drying. (
  • From an inventory of interactions derived from the x-ray crystal structure of a protein, the stabilizing contribution of each amino acid be calculated using the free energies determined from thermodynamic studies of model systems. (
  • Research in my lab focuses on atomic-level mechanisms of protein regulation, protein-ligand interactions, and computer-aided drug design. (
  • NMR spectroscopy will be employed for accessing the structures, dynamics of the "excited state" protein conformations and protein-protein interactions. (
  • Identifying structural hotspots, understanding drug/protein or protein/protein interactions or determining the structural conformational changes occurring during formulation and storage are key questions posed during the development of a biotherapeutic. (
  • Dr. Bob Galvin, VP Biopharma at Bruker Daltonics, commented: "With the new Bruker HDX Solution, we are further strengthening our biologics characterization portfolio, and enable biopharma researchers to gain greater insights into protein conformation and protein interactions more quickly, more reliably and with greater confidence. (
  • CABS-dock is a versatile and efficient tool for modeling the structure, dynamics and interactions of protein complexes. (
  • The docking protocol employs a coarse-grained representation of proteins, a simplified model of interactions and advanced protocols for conformational sampling. (
  • Motivation: Proteinâ€"protein interactions play vital functional roles in various biological phenomena. (
  • The data suggest that the architecture of membrane proteins is strongly dependent upon apolar lipid-protein and/or lipid-sensitive protein-protein interactions. (
  • Tel Aviv, Israel, May 19, 2011 - Compugen Ltd. (NASDAQ: CGEN) announced today the development of a method to identify novel therapeutic candidates to interfere with disease associated protein conformations and protein-protein interactions. (
  • Detecting these hidden conformations extends our ability to design novel peptide product candidates that interfere with disease associated conformations (DAC) and protein-protein interactions (PPI), in addition to providing important new insights for our protein therapeutic product candidate discovery activities. (
  • A series of six such peer-reviewed articles, describing various Compugen in silico methodologies for the design of peptides required for blocking either disease-associated conformations or protein-protein interactions, have been published to date. (
  • Proteins are dynamic entities, which can adopt a series of different conformations (i.e. three dimensional structures), which determine their activity and interactions with other proteins or molecules. (
  • Changes in conformation and interactions with small molecules are, of course, intrinsic to the central role played by proteins in biology. (
  • [1] To be able to perform their biological function, proteins fold into one or more specific spatial conformations driven by a number of non-covalent interactions such as hydrogen bonding , ionic interactions , Van der Waals forces , and hydrophobic packing. (
  • The difficulty of assessing this question is shown to be partly the result of the inability of the sequential truncation approach usually employed to account for interactions between the conformations of the macrocycle and its substituents and an alternative approach is suggested. (
  • Time-regulated secretion and structural disorder of mussel adhesive proteins appear essential for optimizing extended nonspecific surface interactions and byssus' assembly. (
  • Also, the context of one such residue shows that even a designed highly stable protein can harbor substantial unfavorable interactions. (
  • Similar to metal scaffolding which provides construction workers with access points to a building, scaffolding proteins mediate interactions between proteins situated on the membrane of the human cell. (
  • The molecular structure of each of the four individual PDZ domains has been solved using X-ray crystallography and NMR spectroscopy, however the overall arrangement of the domains in the protein as well as their interactions was not yet understood. (
  • Roles of electrostatics and conformation in protein-crystal interactions. (
  • Here, we demonstrate the application of crosslinking mass spectrometry to identify protein structural features and interactions in tissue samples, providing systems structural biology insight into protein complexes as they exist in the mouse heart. (
  • This includes insights into multiple conformational states of sarcomere proteins, as well as interactions among OXPHOS complexes indicative of supercomplex assembly. (
  • The extension of crosslinking mass spectrometry analysis into the realm of tissues opens the door to increasing our understanding of protein structures and interactions within the context of the greater biological system. (
  • The structure revealed that the 101F and motavizumab epitopes are present in the postfusion state and that their conformations are similar to those observed in the antibody-bound peptide structures. (
  • The 35 amino acid cytoplasmic peptide in PLP, which distinguishes this protein from DM-20, imparts a sensitivity to mutations in extracellular domains. (
  • The general relations between protein conformation and the optical activity of peptide chromophores are outlined and applied to the analysis of the optical rotatory dispersion and circular dichroism of the plasma membranes of human erythrocytes and Ehrlich ascites carcinoma cells. (
  • It has been found that the affinity of peptide fragments of the human Pin1 WW domain for Cu(II) ions depends on its conformation. (
  • It was found that the most stable complexes with Cu 2+ ions are formed with peptide 2, which has the most bent conformation. (
  • Proteins form by amino acids undergoing condensation reactions , in which the amino acids lose one water molecule per reaction in order to attach to one another with a peptide bond . (
  • By convention, a chain under 30 amino acids is often identified as a peptide , rather than a protein. (
  • The primary structure is held together by peptide bonds that are made during the process of protein biosynthesis . (
  • It is strictly recommended to use the words "amino acid residues" when discussing proteins because when a peptide bond is formed, a water molecule is lost, and therefore proteins are made up of amino acid residues. (
  • The characteristic 3-dimensional shape of a protein, including the secondary, supersecondary (motifs), tertiary (domains) and quaternary structure of the peptide chain. (
  • In this paper, we have used PROTOFOLD to predict the final conformation of a small peptide chain segment, an alpha helix, and the Triponin protein chains from a denatured configuration. (
  • Proteins are chains of amino acids joined together by peptide bonds. (
  • Although it was once thought that globular protein molecules unfold completely in the interface, it has now been established that many proteins can be recovered from films in the native state. (
  • This work constitutes a first step into assessing not only the generality but also the significance of specific water binding in globular proteins. (
  • Dill, K.: Theory for the folding and stability of globular proteins. (
  • It is concluded that the proteins of these membranes are "globular" and that they have considerable helical content. (
  • Accumulating evidence suggests that solution-phase conformations of small globular proteins and large molecular protein assemblies can be preserved for milliseconds after electrospray ionization. (
  • In contrast, smaller globular proteins appear to adopt a multitude of gas-phase conformations depending on the condition of the electrospray process and the amount of time that elapses before detection. (
  • Although this conformational ensemble likely extends beyond that present in solution, the gas-phase conformations of globular proteins offer a window into the nonnative and solvent-free conformational landscape 5 including intermediates along the folding pathway and trapped misfolded species. (
  • Furthermore, several recent experimental studies suggests that the solution-phase conformers of even small globular proteins can be largely preserved for 30-60 milliseconds following ESI 6 - 10 . (
  • Thus, sensitive analytical tools are needed for the rapid characterization of conformations of both small globular proteins and large macromolecular complexes in the gas-phase. (
  • In contrast to globular proteins such as RNase H, repeat proteins are tandem arrays of repeating structural units that have no long-range contacts. (
  • Is the Subject Area "Protein structure prediction" applicable to this article? (
  • Among specific topics are the local structure alphabets, integrative protein fold recognition by alignment and machine learning, hybrid methods for protein structure prediction , and the conformational search for the protein native state. (
  • et al explain protein structure prediction , Bayesian networks as static models of regulatory pathways, metabolic control theory, dynamic modeling of biological pathways, and gene silencing. (
  • This work describes the successes and limitations of various computational methods for protein structure prediction and their assessment, including template-based approaches, structure alignment and indexing, protein features prediction, and de novo methods. (
  • To that end, this reference sheds light on the methods used for protein structure prediction and reveals the key applications of modeled structures. (
  • Thus the foundations are set for a novel encoding based on L-systems for evolutionary approaches to both the Protein Structure Prediction and Inverse Folding Problems. (
  • Khimasia, M., Coveney, P.: Protein structure prediction as a hard optimization problem: The genetic algorithm approach. (
  • As protein structures correlate with characteristic functions, structure comparison allows classification and prediction of proteins of undefined. (
  • This new in silico method relies on the prediction of hidden conformations of the proteins of interest, which is the subject of a scientific paper to be published in the journal Bioinformatics, and is now available online at this link . (
  • This is accomplished through in silico prediction based on structures of other proteins that are remotely related to the target proteins of interest. (
  • Algorithms, enabling the appropriate weighting of the structural information extracted from the various remote homologous proteins, are a key component of the new method, resulting in the prediction of previously unknown conformations for the target protein. (
  • Protein residue-residue contact prediction is important for protein model generation and model evaluation. (
  • Here we develop a conformation ensemble approach to improve residue-residue contact prediction. (
  • Even after many years of intense attention and development, de novo protein structure prediction remains a difficult and open problem. (
  • This paper presents an efficient and novel computational protein prediction methodology called kineto-static compliance method. (
  • The results show that torques in each joint are minimized to values very close to zero, which demonstrates the method's effectiveness for protein conformation prediction. (
  • The Chou-Fasman method is an empirical technique for the prediction of tertiary structures in proteins, originally developed in the 1970s by Peter Y. Chou and Gerald D. Fasman. (
  • List of protein structure prediction software Chou PY, Fasman GD (1974). (
  • Protein structure prediction is the inference of the three-dimensional structure of a protein from its amino acid sequence-that is, the prediction of its secondary and tertiary structure from primary structure. (
  • Structure prediction is different from the inverse problem of protein design. (
  • the performance of current methods is assessed in the CASP experiment (Critical Assessment of Techniques for Protein Structure Prediction). (
  • A continuous evaluation of protein structure prediction web servers is performed by the community project CAMEO3D. (
  • Here we examine these structures using a structural bioinformatics approach to understand how the conformation of the activation segment controls kinase activity. (
  • Is the Subject Area "Structural proteins" applicable to this article? (
  • The structural preservation of neutralizing epitopes in the postfusion state suggests that this conformation can elicit neutralizing antibodies and serve as a useful vaccine antigen. (
  • The research programs encompass an integrated structural biology and biophysics approach to understand protein dynamics, protein recognition and interaction by investigating intermediate protein active conformations (excited state), protein dynamics modulation and the subsequently changes of its activities. (
  • Motivation: Most methods that are used to compare protein structures use three-dimensional (3D) structural information. (
  • At the same time, it has been shown that a 1D string representation of local protein structure retains a degree of structural information. (
  • Efficient and automated large-scale detection of structural relationships in proteins with a flexible aligner. (
  • The technique is shown to have some advantages over differential scanning calorimetry for the study of structural change, and can also be used to measure the affinity of carbohydrate binding proteins, such as Lectin, with monosaccharides. (
  • The important structural and functional roles played by proteins in the proper functioning of cellular processes cannot be overstated. (
  • To comprehensively understand their functional behaviors, structural models derived from experimental data have been developed and these models have played a significant role in explaining the functional mechanisms of proteins. (
  • To incorporate dynamics into structural representations, ensembles of conformations, instead of a single structure, are used frequently in recent literature and are found to be successful in explaining the functions of many proteins. (
  • This is the topic of the scientific field of structural biology , which employs techniques such as X-ray crystallography , NMR spectroscopy , and dual polarisation interferometry to determine the structure of proteins. (
  • A protein generally undergoes reversible structural changes in performing its biological function. (
  • The structural integrity of meningococcal native, micro-fluidized and activated capsular polysaccharides and their glycoconjugates - in the form most relevant to their potential use as vaccines (dilute solution) - have been investigated with respect to their homogeneity, conformation and flexibility. (
  • The structural data for the Fenna-Matthews-Olson (FMO) protein indicate that the bacteriochlorophylls (BChls) display a significant degree of conformational heterogeneity of their peripheral substituents and the protein-induced nonplanar skeletal deformations of the tetrapyrrole macrocycle. (
  • Because there are explicit water molecules in the system, it's possible to identify features like bridging water molecules and those water molecules which are held rigid by the protein and, therefore, should be treated as structural features. (
  • One additional method which does not fall under the umbrella of the three categories mentioned is the extraction of contacts from 3D structural models generated for a protein. (
  • When CSSB group leader Christian Löw and his colleagues were unable to crystallize the scaffolding protein, PDZK1, they did not give up the hope of uncovering detailed structural information about this important protein. (
  • Conformation data may be added to repositories such as ArchDB , European Mouse Mutant Archive , MEROPS , PROSITE , PCDDB , Protein Data Bank in Europe , The Cambridge Structural Database , and wwPDB . (
  • Background: Despite structural reorganization during disease, conformational prion protein epitopes remain undefined. (
  • While modern structural biology technologies have greatly expanded the size and type of protein complexes that can now be studied, the ability to derive large-scale structural information on proteins and complexes as they exist within tissues is practically nonexistent. (
  • The project involves biochemistry in terms of protein expression, purification and establishing protein-protein interaction report systems. (
  • The successful candidate should hold a PhD degree in biochemistry or biophysics (or other related discipline) and has experience in protein expression and purification as well as a proven publication record. (
  • Comparative Analysis of Protein Three-Dimensional Structures and an Approach to the Inverse Folding Problem (T. Blundell). (
  • There are currently at least forty-six unique protein kinase crystal structures, twenty-four of which are available in an active state. (
  • We examine how the polypeptide chain in protein crystal structures exploits the multivalent hydrogen-bonding potential of bound water molecules. (
  • In this study, two new crystal forms and protein structures of CheY are reported. (
  • Secondary structure protein refers to regular repeative sub-structures on the protein backbone. (
  • Using an alignment of fragment strings for comparing protein structures. (
  • Physical contacts between proteins have been revealed using experimental approaches that have solved the structures of protein complexes at atomic resolution. (
  • Background: The total number of known three-dimensional protein structures is rapidly increasing. (
  • Background Protein structures are flexible and often show conformational changes upon binding to other molecules to exert biological functions. (
  • CATHEDRAL: A Fast and Effective Algorithm to Predict Folds and Domain Boundaries from Multidomain Protein Structures. (
  • Crystal structures of the MalFGK 2 -MalE-maltose complex in a so-called "pretranslocation" ("pre-T") state with a partially closed conformation suggest that the formation of this MalE-stabilized intermediate state is a key step leading to the outward-facing catalytic state. (
  • Ideal values of bond angles and lengths used as external restraints are crucial for the successful refinement of protein crystal structures at all but the highest of resolutions. (
  • However, recent work has shown that the ideal values are, in fact, sensitive to local conformation, and as a first step toward using such information to build more accurate models, ultra-high resolution protein crystal structures have been used to derive a conformation-dependent library (CDL) of restraints for the protein backbone (Berkholz et al. (
  • Protein structures range in size from tens to several thousand amino acids. (
  • The alternative structures of the same protein are referred to as different conformational isomers , or simply, conformations, and transitions between them are called conformational changes . (
  • In addition, the computational methods are generally biased toward lowest energy structures by design and miss these high energy but functionally important conformations. (
  • The native structure of a protein is important for its function, and therefore methods for exploring protein structures have attracted much research. (
  • SAs approximate conformations of protein backbones and code the local structures of proteins as one-dimensional sequences. (
  • Applying PB-based approaches to biological systems such as the DARC protein, the human αIIb β3 integrin and the KISSR1 protein highlighted the major interest of PBs in understanding local deformations of large protein structures. (
  • Even when there are a series of related crystal structures in differing conformational states, this still does not give the complete picture of all the available protein conformations or indeed any information on the protein energy landscape, so the energy barriers and population states of the observed conformations remain unknown. (
  • Figure 1: Crystal structures 1sw2 (top right) and 1sw5 (top left) modeled in Flare™ [1] showing the protein movement observed upon ligand binding for the osmoprotection protein ProX [2] . (
  • Molecular dynamics calculations help to map the energy landscape by solvating the protein with explicit water molecules then adding energy into the system to allow it to move, generating an ensemble of protein structures. (
  • During this process snapshots of the protein are taken at predefined time steps, calculating a series of protein structures which are likely to be representative of the biologically relevant protein conformations. (
  • Tracking flavin conformations in protein crystal structures with Raman spectroscopy and QM/MM calculations. (
  • The unusual BII phosphate conformation detected in B-DNA structures was found sequence dependant and associated to large changes in inter base-pair helical parameters. (
  • To understand how two proteins that share identical structures can function in such different environments, we looked for differences in their energetics by comparing equilibrium mimics of their high-energy intermediates. (
  • 0°). We report that high-energy conformations with ϕ ~ 0°, normally expected to occur only as fleeting transition states, are stably trapped in certain highly resolved native protein structures and that an analysis of these residues provides a detailed, experimentally derived map of the bond angle distortions taking place along the transition path. (
  • Now, state-of-the-art energetics calculations ( 5 ) and the distributions of ϕ,ψ angles seen in high-resolution protein structures ( 6 , 7 ) recapitulate the main features of the original ϕ,ψ plots remarkably well. (
  • Electron spin relaxation data from five ferric proteins are analyzed in terms of the fractal model of protein structures. (
  • The results lead to a characterization of protein structures by a single parameter, the fractal dimension, d. (
  • The method is based on analyses of the relative frequencies of each amino acid in alpha helices, beta sheets, and turns based on known protein structures solved with X-ray crystallography. (
  • The original Chou-Fasman parameters were derived from a very small and non-representative sample of protein structures due to the small number of such structures that were known at the time of their original work. (
  • The secondary structures are tightly packed in the protein core in a hydrophobic environment. (
  • Other α helices buried in the protein core or in cellular membranes have a higher and more regular distribution of hydrophobic amino acids, and are highly predictive of such structures. (
  • We have considered the conformation of the proline itself, the relative occurrence of cis and trans peptides preceding proline residues, the influence of proline on the conformation of the preceding residue and the conformations of various proline patterns (Pro-Pro, Pro-X-Pro, etc. (
  • GPCRs respond to various ligands extracellularly, such as amines, peptides, hydrophobic effectors, hormones, small proteins and volatiles, which allows the receptors to activate the G-proteins intracellularly. (
  • Here, Fӧrster resonance energy transfer (FRET) biosensors have been developed by pairwise tethering a GPCR to G protein peptides to probe conformational changes at controlled concentrations in live cells. (
  • CGEN ) announced today the development and validation of its Blockers of Disease-Associated Conformation (DAC Blockers) platform, a new discovery platform for the identification of peptides that block proteins from adopting their disease-associated conformations. (
  • The newly developed DAC Blockers platform has been designed to identify segments in proteins of interest that, if introduced therapeutically as synthetic peptides, would block specific conformational changes of such proteins, and thereby prevent them from adopting disease-associated conformations and related activities. (
  • Therefore, molecules that can target and block these disease-associated conformations, such as the peptides identified through the use of Compugen's DAC Blockers platform, have potential applications in many different therapeutic areas. (
  • However, the model is inconsistent with older observations from Krimm's group as well as a wealth of spectroscopic techniques that demonstrate the presence of well-defined backbone structure within the unfolded states of proteins and peptides. (
  • Protein molecules in an interface, because of Brownian motions (molecular vibrations), occupy much more space than do those in the film after the application of pressure. (
  • The Brownian motion of compressed molecules is limited to the two dimensions of the interface, since the protein molecules cannot move upward or downward. (
  • The motion of protein molecules at the air-water interface has been used to determine the molecular weight of proteins. (
  • A large group of proteins has been called conjugated proteins , because they are complex molecules of protein consisting of protein and nonprotein moieties. (
  • Gow and Lazzarini, 1996 ), but precisely how these molecules may interact and how they may influence the conformation of one another is at present unknown. (
  • Offering sensitivity it is designed to allow protein molecules with a hydrodynamic radius down to 0.3 nm to be measured at concentrations of 0.1 mg/ml or less. (
  • The ability to identify unknown protein conformations and predict molecules that can interfere with, and thereby block, these conformations greatly enhances discovery of novel therapeutic agents. (
  • Recently, we have been able to reproduce the binding equilibrium of a small molecule to a protein in terms of its free energy, and to decompose this quantitatively into parts, a binding energy and a cratic free energy, the latter corresponding to the loss of positional and orientational freedom when two molecules form a complex. (
  • The HN protein is responsible for binding to sialic acid-containing cellular molecules and for enzymatic cleavage of the sialoconjugate, while the F protein is involved in envelope-to-cell and cell-to-cell fusion (cell fusion) ( 9 , 31 ). (
  • Fluorine nuclear magnetic resonance techniques have been used to study conformational processes in two proteins labeled specifically in strategic regions with covalently attached fluorinated molecules. (
  • Finally, we describe small molecules that selectively bind to and stabilize the wild-type conformation of ARNT PAS-B. These studies form a toolkit for studying fragile protein folds and could enable ways to modulate the biological functions of such fragile folds, both in natural and engineered proteins. (
  • Small-angle X-ray scattering (SAXS) is an x-ray based technique that allows the analysis of proteins and other molecules in solution. (
  • Tanaka, M., Machida, Y., and Nukina, N. A novel therapeutic strategy for polyglutamine diseases by stabilizing aggregation-prone proteins with small molecules. (
  • It is known that G-protein-coupled receptors exhibit several distinct low-energy conformations, each of which might favor binding to different ligands and/or lead to different downstream functions. (
  • G-protein-coupled receptors (GPCRs) [also referred to as seven-transmembrane receptors (7TMRs)] are integral membrane proteins that play a central role in transmembrane (TM) signal transduction. (
  • G protein-coupled receptors (GPCRs) traverse the plasma membrane seven times and produce intracellular effects through interaction with G proteins. (
  • G-protein coupled receptors (GPCRs) are a diverse super-family of proteins located within the plasma membrane of eukaryotic cells which have a common architecture consisting of seven-transmembrane (7-TM) segments, connected by extracellular (ECL) and intracellular (ICL) loops. (
  • The small Secretin-receptor family is structurally and functionally diverse and includes receptors for polypeptide hormones, and for Drosophila proteins that regulate stress responses and longevity 7 . (
  • Many of the receptors have accessory proteins which either facilitate trafficking to the plasma membrane or influence the specificity of the ligand 8 . (
  • Simple methods to detect the selective activation of G proteins by G protein-coupled receptors remain an outstanding challenge in cell signaling. (
  • These data advance our understanding of the site and nature of the ligand-protein interaction for GluN2C-selective positive allosteric modulators for NMDA receptors. (
  • In: G Protein-Coupled Receptors Part A. Methods in Cell Biology. (
  • G protein-coupled receptors (GPCRs) are membrane proteins critical in cellular signaling, making them important targets for therapeutics. (
  • Here, we demonstrate the importance of polar transmembrane residues conserved within family B G protein-coupled receptors, not only for protein folding and expression, but also in controlling activation transition, ligand-biased, and pathway-biased signaling. (
  • Serpentine receptors relay hormonal or sensory stimuli to heterotrimeric guanine nucleotide-binding proteins (G proteins). (
  • In most G protein-coupled receptors (GPCRs), binding of the agonist ligand elicits both stimulation of the G protein and endocytosis of the receptor. (
  • Two different mutant receptors both constitutively activate G protein-mediated responses, but one (F251A) is endocytosed only in response to ligand stimulation, while the other (NQ) is constitutively internalized in the absence of ligand. (
  • Influence of proline residues on protein conformation. (
  • To study the influence of proline residues on three-dimensional structure, an analysis has been made of all proline residues and their local conformations extracted from the Brookhaven Protein Data bank. (
  • Our results show a significant increase in the diversity of the conformations sampled for proteins consisting of up to 500 residues when applied to a specific robotics-inspired algorithm for conformational sampling. (
  • Proteins The ________ helix is a common motif in the secondary structure of proteins, a right-handed coiled conformation, resembling a spring, in which every backbone N-H group donates a hydrogen bond to the backbone carbonyl group of the amino acid four residues earlier. (
  • The effects of cyclodextrins on the conformation of proteins can be classified to those on the main chains as well as those on the side chains of amino acid residues of proteins. (
  • Those effects of cyclodextrins associated with the side chains of proteins are interpreted as a result of inclusions of the side chains of aromatic amino acid residues. (
  • Using homology modelling and molecular dynamics simulations, we find that all mussel adhesive proteins are largely unordered, with Pvfp-5 adopting a disordered structure and elongated conformation whereby all Dopa residues reside on the protein surface. (
  • Our model [Beta]-barrel membrane protein, OmpA, contains five native anchoring Tryptophan residues. (
  • The spectroscopic properties of trp residues are highly sensitive to the local environment, making it an ideal probe for membrane protein folding studies. (
  • Cyst(e)ine residues of bovine white-matter proteolipid proteins. (
  • Cyst(e)ine residues of bovine white-matter proteolipid proteins were characterized in a highly purified preparation. (
  • From a total of 10.6 cyst(e)ine residues/molecule of protein, as determined by performic acid oxidation, 2.5-3 thiol groups were freely accessible to iodoacetamide, iodoacetic acid and 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB), when the proteins were solubilized in chloroform/methanol (C/M) (2:1, v/v). The presence of lipids had no effect on thiol-group exposure. (
  • Cyst(e)ine residues were also characterized in the different components [PLP (principal proteolipid protein), DM20 and LMW (low-Mr proteins)] of the proteolipid preparation. (
  • Table 3 Binding of secreted forms of RSV F protein to conformation-indicating antibodies following transfection of modified mRNAs into Expi293F cells. (
  • We show by immunoprecipitation of C. pneumoniae with GZD1E8 and RR-402 MAbs and by mass spectrometry analysis of immunoprecipitated proteins that both antibodies GZD1E8 and RR-402 recognize the MOMP of C. pneumoniae and that this protein is localized on the surface of the organism. (
  • Synthetic drugs, natural compounds, and antibodies are widely explored for potential to stop pathogenic protein assembly or to promote fibril degradation and clearance, but to date have had little success in relieving symptoms in clinical trials. (
  • When antibodies from women urogenitally infected with C. trachomatis were reacted with the plasmid proteins, all 8 pORFs were positively recognized by one or more human antibody samples with the recognition of pORF5 protein (known as pgp3) by most antibodies and with the highest titers. (
  • The pgp3 conformation is likely maintained by the C-terminal 75% amino acid sequence since further deletion blocked the binding by the human antibodies and two conformation-dependent mouse monoclonal antibodies. (
  • More importantly, the human anti-pgp3 antibodies are highly conformation-dependent. (
  • The Laboratory of Protein Conformation and Dynamics integrates complementary biophysical and biochemical techniques to understand the molecular mechanisms of amyloid formation. (
  • My research is focused on discovering the macromolecular structure and dynamics of proteins-defining conformational states essential for function and understanding transitions between these states. (
  • The relationship between functional conformation changes and thermal dynamics of proteins is investigated with the help of the torsional network model (TNM), an elastic network model in torsion angle space that we recently introduced. (
  • We interpret these features as the result of natural selection favoring the intrinsic protein dynamics consistent with functional conformation changes. (
  • This deep relationship between the thermal dynamics of a protein, represented by its normal modes, and its functional dynamics can reconcile in a unique framework the two models of conformation changes, conformational selection and induced fit. (
  • The paradigm "structure drives function" had been active for many years until recent evidence suggested that the complex functions of proteins could not be fully explained by a single structure and dynamics played a very important role in deciphering their functions. (
  • This representation has the advantage of representing the dynamics using only a few conformational states, thereby minimizing the potential of over-fitting, while capturing the dynamics of the protein that a single average structure misses. (
  • Understanding protein structure and dynamics is essential for understanding their function. (
  • Understanding the connection between protein structure, dynamics and function can contribute substantially to our understanding of cellular processes involving proteins. (
  • The question of how the structure and dynamics of proteins relate to their function has challenged scientists for several decades but still remains open. (
  • These energy wells are then sampled locally using a finer grid in conformational space to find a locally minimized conformation in each energy well, which can be further relaxed using molecular dynamics (MD) simulations. (
  • Molecular dynamics can be useful for assessing the energetic stability of proteins and identifying available conformations and, therefore, analyzing available binding pockets. (
  • In order to get the most insight from molecular dynamics it's important to have background understanding of the system of interest and of protein movements in general. (
  • This is when molecular dynamics can help fill in the missing pieces of the conformational puzzle and protein energy landscape. (
  • Assessing protein stability: How can molecular dynamics help? (
  • Analysis of these conformations from a molecular dynamics calculation can enable the assessment of protein movements and the identification of different lower energy conformational states for the system. (
  • The current fashion for using pure molecular dynamics calculations is to run multiple simulations to generate a collection of energy landscapes for exploring the available conformations. (
  • This dissertation focuses on the folding dynamics of a bacterial membrane protein, Outer Membrane Protein A (OmpA), using fluorescence and Ultraviolet resonance Raman spectroscopy. (
  • Taking a closer look at these intermediate regions will ultimately help us to fully understand the function and dynamics of PDZK1 as well that of other scaffolding proteins," notes Nelly Hajizadeh, one of the first authors of the study. (
  • They differ from other 7-TM proteins in their ability to activate guanine-nucleotide binding proteins or β-arrestin and so initiate a signalling cascade. (
  • The results highlight the unique role of proline in determining local conformation. (
  • We find that different mutations and ligands stabilize different conformations. (
  • The proteolipid protein gene products DM-20 and PLP are adhesive intrinsic membrane proteins that make up ≥50% of the protein in myelin and serve to stabilize compact myelin sheaths at the extracellular surfaces of apposed membrane lamellae. (
  • In particular, since the active-state conformations are higher in energy (less stable) than inactive-state conformations, they are difficult to stabilize. (
  • We observed that in the presence of Prp8, the population of the high FRET conformation of U2-U6 that is thought to be the active conformation increased indicating that one of the functions of Prp8 would be to stabilize the active site conformation of the spliceosome. (
  • Although E2 proteins contact the two half-sites ACCG/CGGT and not the N 4 spacer, the affinity predominantly depends on the spacer base composition: as examples, a sequence containing the ACGT spacer is well-recognized by the bovine PV-E2 protein but makes low affinity target for human PV-E2, whereas the inverse is found for the AAAC spacer. (
  • At the East Asian Biophysical Society meeting in Okinawa (12-16 November 2006) Kouhei Shiba, from Sysmex discussed the benefits of using the Malvern Zetasizer Nano to study conformational changes in proteins. (
  • The PDK1-substrate interaction model describes, at a molecular level, the mechanism used by PDK1 to sense the conformation of its substrates. (
  • Fluorinated C3-benzamido substituents induced a shift in the side-chain conformation of R144 to allow for an entropically favored electrostatic interaction between its guanidine group and the 2- O -sulfate of the ligand. (
  • Together, RCC1's shape and importin a3's ability to change its conformation drive this selective interaction. (
  • We elucidate a strong electrostatic interaction between BSA and the SPIONs, although the secondary structure of the protein is not affected. (
  • This specific interaction further rationalizes the kinetics of the phototransduction cascade and provides a general hypothesis to explain the mechanism of interaction of RGS proteins with other G proteins. (
  • The last three decades has seen some important advances in our ability to represent the conformation of proteins in solution on the basis of hydrodynamic measurements. (
  • Rapid and robust methods are required to quantify the effect of hydrodynamic shear on protein conformation change. (
  • Random coil has a long history of interpreting experimental results on unfolded proteins, in particular those from hydrodynamic and SAXS measurements of the radius of gyration (R g ). (
  • In recent years, biopharmaceutical characterization requires deeper understanding of the conformational structure of biotherapeutic proteins, and how they are affected for example by pH, temperatures or other stress. (
  • The Zetasizer Nano is a protein characterization tool. (
  • The role of such intermediates is a matter of considerable debate, but it is clear that characterization of these partially folded species is crucial for understanding protein folding and function. (
  • Telling, Glenn C. Characterization of Conformation-dependent Prion Protein Epitopes. (
  • In the CNS of tetrapods, compact myelin is maintained as a multilamellar sheath by the combined action of two sets of highly abundant membrane proteins, the myelin basic proteins and the proteolipid proteins (DM-20/PLP). (
  • Proteins, when forming an interfacial film, are present as a monomolecular layer-i.e., a layer one molecule in height. (
  • The application of lateral pressure on a protein film causes it to increase in thickness and finally to form a layer with a height corresponding to the diameter of the native protein molecule. (
  • Docking simulations illustrated how the TnC molecule undergoes significant conformational transition on complex formation, a phenomenon that can be modeled only when protein flexibility is properly accounted for. (
  • The importin a3 molecule, or "car," is one of a family of importin proteins that help ferry other proteins across the nuclear membrane where they can alter the course of DNA transcription. (
  • In our SMD project we are studying the extraction of a non-covalently bound small molecule from a protein, by a user-specified tug, through any of several likely exit routes, and this is followed by batch calculations of the energetics experienced by a molecule moving naturally along such a path, i.e., by diffusion, rather than as the result of an artificial tug. (
  • Protein structure is the three-dimensional arrangement of atoms in an amino acid -chain molecule . (
  • In order to test whether or not Prp8 stabilizes the active-site conformation, we carried out single-molecule fluorescence resonance energy transfer (smFRET) experiments with catalytically important snRNAs U2 and U6 and Prp8. (
  • Although bis-ANS itself did not alter the conformation of VWF, it stabilized protein conformation once it bound the sheared molecule. (
  • Most of the current docking procedures are focused on fine conformational adjustments of assembled complexes and fail to reproduce large-scale protein motion. (
  • SCPC: a method to structurally compare protein complexes. (
  • Numerous studies have demonstrated that protein-ligand complexes and even large functional macromolecular protein assemblies can retain their non-covalent bonding in the gas-phase ( 1 - 4 and references therein). (
  • We demonstrate how these are providing great insights into complex issues such as the conformation of immunoglobulins and other multi-domain complexes. (
  • As with the recently published finding for Hib-TT complexes, it is the carbohydrate component that dictates the solution behaviour of these glycoconjugates, although the lower intrinsic viscosities suggest some degree of compaction of the carbohydrate chains around the protein. (
  • hsp70-protein complexes. (
  • Complexes between hsp70 and unfolded substrate proteins were isolated by size-exclusion high performance liquid chromatography. (
  • performed proximity biotinylation assays in murine Schwann cells with wild-type and various mutant forms of Merlin that could not associate with the plasma membrane or were locked in different conformations. (
  • This application note illustrates that the SYNAPT G2 HDMS System, which provides an orthogonal separation technique with ion mobility mass spectrometry, can clearly separate different conformations of equine cytochrome c within minutes, matching that of published work. (
  • Biomolecules introduced to a mass spectrometer by electrospray ionization (ESI) exhibit a number of different conformations depending on charge states, eluent pH, and size. (
  • Understanding the higher order structure of biomolecules is important for the biopharmaceutical industry because different conformations may affect biological activity. (
  • It is often time-consuming to separate or identify different conformations. (
  • Different conformations of isobaric biomolecules cannot be separated by mass spectrometric resolution alone. (
  • This work describes how different conformations of equine cytochrome c can be clearly separated within minutes. (
  • By selecting a single charge state of biomolecule ions, ions with different conformations can be separated. (
  • Proteins are dynamic entities and can adopt a series of different conformations. (
  • Additionally, UVRR was used to monitor changes in trp environmental hydrophobicity, hydrogen bonding, and dihedral torsion angle in different conformations of OmpA. (
  • The various models capture slightly different conformations and contain complementary information which can be pooled together to capture recurrent, and therefore more likely, residue-residue contacts. (
  • In addition, robotics-inspired algorithms depend on defining useful perturbation strategies for exploring the conformational space, which is a difficult task for large proteins because such systems are typically more constrained and exhibit complex motions. (
  • Since this dynamic property of proteins is important for their function in healthy and diseased states, a broad view of a protein's conformational space is crucial in many aspects of drug discovery. (
  • We present a hierarchical clustering and algebraic topology based method that detects regions of interest in protein conformational space. (
  • Characterizing the conformational space of proteins is crucial for understanding the way they perform their function. (
  • In this work we use both algebraic topology and dimensionality reduction methods to explore and characterize the conformational space of proteins. (
  • In previous work [ 18 , 19 ] we used persistent homology to explore the conformational space of proteins and detect regions of interest that may correspond to local minima, which are hard to detect experimentally due to the relatively short time the protein spends in them. (
  • In a C/M solution of purified proteolipid proteins, SDS did not increase the number of reactive thiol groups, but the cleavage of one disulphide bridge made it possible to alkylate six more groups. (
  • However, various GPCRs differ sufficiently in the tilts of the TMHs that this method need not predict the optimum conformation starting from any other template. (
  • This suggests that inverse agonists are not merely "the opposite of agonists," but instead may serve as useful tools to investigate ligand-specific conformations of GPCRs. (
  • The activation of GPCRs is central to their function, requiring multiple conformations of the GPCRs in their activation landscape. (
  • After two German chemists, Emil Fischer and Franz Hofmeister, independently stated in 1902 that proteins are essentially polypeptides consisting of many amino acids , an attempt was made to classify proteins according to their chemical and physical properties, because the biological function of proteins had not yet been established. (
  • Background: CRANKITE is a suite of programs for simulating backbone conformations of polypeptides and proteins. (
  • Proteins are polymers - specifically polypeptides - formed from sequences of amino acids , the monomers of the polymer. (
  • The fundamental event in prion diseases seems to be a conformational change in cellular prion protein (PrP C ) whereby it is converted into the pathologic isoform PrP Sc . (
  • After several groups determined the genetic sequence of that protein, Prusiner realized that it was a fragment of a normal protein (prion protein or PrP), the function of which is still uncertain, which is found in healthy nerve cells. (
  • Significance: Our studies address how denatured conformational epitopes remain functional, provide insights into normal and disease-related prion protein, and expand epitope tagging options. (
  • We also tested for the presence of translocation signals that enable insertion of these proteins into rough endoplasmic reticulum (RER) membranes. (
  • It should then be expected that T-cell recognition of protein antigens in vitro will be independent of protein conformation. (
  • Our results demonstrate that the conformation of antigens in VLPs is of critical importance for optimal stimulation of protective as well as durable immune responses. (
  • Many different computational approaches for protein structure comparison apply the secondary structure elements. (
  • The accurate assignment of the secondary structure of proteins from protein atom coordinates underlies the analysis of protein structure and function. (
  • Using this protein as a test case, we advance the concept of a "fragile fold", a protein fold that can reversibly rearrange into another fold that differs by a substantial number of hydrogen bonds, entailing reorganization of single secondary structure elements to more drastic changes seen in metamorphic proteins. (
  • From these frequencies a set of probability parameters were derived for the appearance of each amino acid in each secondary structure type, and these parameters are used to predict the probability that a given sequence of amino acids would form a helix, a beta strand, or a turn in a protein. (
  • How good are predictions of protein secondary structure? (
  • citation needed] The protein structure can be considered as a sequence of secondary structure elements, such as α helices and β sheets, which together constitute the overall three-dimensional configuration of the protein chain. (
  • The α helix is the most abundant type of secondary structure in proteins. (
  • One counterexample is the intrinsic disorder found in a significant number of functional proteins and protein regions. (
  • Our results confirm the hypothesis that the spacer flexibility determines the affinities for PV-E2 proteins and, moreover, precise the nature of this flexibility: a dramatic intrinsic instability of the non-contacted dinucleotide backbones. (
  • The core of the suite is an efficient Metropolis Monte Carlo sampler of backbone conformations in continuous three-dimensional space in atomic details. (
  • In pioneering work, Ramachandran and co-workers ( 4 ) introduced the ϕ and ψ torsion angles to describe protein backbone conformations (see Fig. 1 , A and B), defining some conformations as "allowed" and others as "disallowed" due to collisions between atoms. (
  • This unanticipated information lays to rest any uncertainty about whether such transitions are possible and how they occur, and in doing so lays a firm foundation for theoretical studies to better understand the transitions between basins that have been little studied but are integrally involved in protein folding and function. (
  • Crystallographic analyses have shown that polypeptide fragments representing the HR1 domain of the F protein of simian virus 5 (SV5) or human respiratory syncytial virus can form a trimeric coiled-coil structure, to which three antiparallel helices of the polypeptide fragments representing the HR2 domain can bind ( 1 , 33 , 60 ). (
  • On the other hand, an electron microscopic study of purified human respiratory syncytial virus F protein has indicated that the lollipop-shaped rod observed in the purified F protein possibly represents the "postfusion" conformation and harbors the antiparallel trimeric coiled-coil structure in the stem region ( 5 ), which is consistent with the conclusion drawn from the crystallographic study ( 60 ). (
  • It is known that specific conformations are preferentially susceptible to biological activity. (
  • Proteins are commonly the first biomolecules that NPs encounter when they interact with biological systems either in vitro or in vivo . (
  • Randolph Hampton of University of California, San Diego, introduced the audience to his lab's work on quality control pathways, which serve to regulate cellular protein levels by proteasome degradation. (
  • G proteins regulate intracellular signaling by coupling a cycle of guanine nucleotide binding and hydrolysis to transient changes of cellular functions. (
  • During protein folding and as part of some conformational changes that regulate protein function, the polypeptide chain must traverse high-energy barriers that separate the commonly adopted low-energy conformations. (
  • We have previously described how a single point mutation can enable a well-folded protein domain, one of the two PAS (Per-ARNT-Sim) domains of the human ARNT (aryl hydrocarbon receptor nuclear translocator) protein, to interconvert between two conformers related by a slip of an internal β strand. (
  • The E46K genetic missense mutation of the wild-type α-synuclein protein was recently identified in a family of Spanish origin with hereditary Parkinson's disease. (
  • How the amino acid sequence of a protein determines its three-dimensional structure is a major problem in biology and chemistry. (
  • Researchers reveal that the protein RCC1's overall structure, not its distinct amino acid sequence, determines whether it's fast-tracked into nuclei. (
  • The primary structure of a protein refers to the sequence of amino acids in the polypeptide chain. (
  • PROTEIN STRUCTURE, QUATERNARY describes the conformation assumed by multimeric proteins (aggregates of more than one polypeptide chain). (
  • These findings suggest that the adsorption of acidic proteins to Ca2+-rich crystal faces of biominerals is governed by electrostatics and is facilitated by conformational flexibility of the polypeptide chain. (
  • However, by heating the cells at 47°C after mild formaldehyde fixation, the epitopes for MAb 6-7 and mAb 21-1 in the WR F protein were exposed and the reactivity of the MAbs with the WR F protein became comparable to their reactivity with L22P. (
  • Specifically, it is proposed that these unique ligands are able to enrich several distinct active receptor conformations, each demonstrating a preference for regulation of a discrete intracellular effector. (
  • The data further suggests that PDK1 interacts with its substrates when they are in a particular conformation (inactive). (
  • We find that the SuperBiHelix conformational ensemble includes the higher energy conformations associated with the active protein in addition to those associated with the more stable inactive protein. (
  • Several novel drugs take advantage of this dynamic nature by binding to a disease-associated protein in its inactive conformation and blocking it from adopting its active form. (
  • To address this problem, we have developed a computationally efficient ActiveGEnSeMBLE method that systematically predicts multiple conformations that are likely in the GPCR activation landscape, including multiple active- and inactive-state conformations. (
  • The sequence of a protein can be determined by methods such as Edman degradation or tandem mass spectrometry . (
  • Paul Muchowski tied chaperones into the growing recognition that large protein aggregates may be a lesser culprit in neurodegenerative diseases than early assemblies, however elusive they may be in vivo. (
  • He started out by noting that today's version of the amyloid hypothesis-protein misfolding leads to amyloids, and somewhere along the process the cell dies-applies to many neurodegenerative diseases. (
  • The term was coined in 1982 by Stanley B. Prusiner, a neurologist at the University of California at San Francisco , who proposed that a new type of pathogen consisting solely of protein is responsible for a school of deadly neurodegenerative diseases called Transmissible Spongiform Encephalopathies (TSEs). (
  • conformation changes are more frequently associated to ligand binding, and in particular phosphorylation, than to pairs of conformations with the same ligands. (
  • We then apply GISA with no restrictions on geometry, to show how it allows identifying rare conformations by finding rare invariant values only. (
  • We earlier reported the BiHelix method for efficiently sampling the (12) 7 = 35 million conformations resulting from 30° rotations about the axis (η) of all seven transmembrane helices (TMHs), showing that the experimental structure is reliably selected as the best conformation from this ensemble. (
  • We find that the topologies of DM-20 and PLP are identical, with both proteins possessing four transmembrane domains and N and C termini exposed to the cytoplasm. (
  • We find that the transmembrane topologies of DM-20 and PLP are identical, with both proteins possessing four transmembrane domains and both N and C termini located within the cytoplasmic compartment. (
  • ActiveGEnSeMBLE starts with a systematic coarse grid sampling of helix tilts/rotations (~ 13 trillion transmembrane domain conformations) and identifies multiple potential active-state energy wells, using the TM3-TM6 intracellular distance as a surrogate activation coordinate. (
  • These studies resulted in increased stability relative to the full-length protein and suggest the absence of the soluble domain may destabilize the unfolded transmembrane domain. (
  • Fewer proteins interacted with the form of Merlin that could not associate with the plasma membrane, and some proteins interacted specifically with the closed conformation. (
  • Here, we present the 2.8-Å crystal structure of the trimeric RSV F ectodomain in its postfusion conformation. (
  • The native conformation of L22P may represent an intermediate between native and postfusion conformations of a typical paramyxovirus F protein. (
  • We also show that human sera from C. pneumoniae -positive donors consistently recognize the MOMP by immunoprecipitation, indicating that the MOMP of C. pneumoniae is an immunogenic protein. (
  • The plasmid-encoded 8 proteins are both expressed and immunogenic with pgp3 as the most immunodominant antigen during chlamydial infection in humans. (
  • Very large aggregates can be formed from protein subunits . (
  • Protein-bound conformation of a specific inhibitor against Candid. (
  • The fractional water occupancy of each was found by comparison of the total number of conformations in the database regardless of the presence or absence of bound water. (
  • Among the previously unidentified Merlin-interacting proteins was the tumor suppressor ASPP2 (also called Tp53bp2), which bound directly to the closed conformation. (
  • To probe the connections between these two proteins, Dr. Cingolani's team first visualized the crystal structure of RCC1 while bound to importin a3. (
  • The vanguard 3,4-dihydroxy-L-phenylalanine (Dopa)-rich protein Pvfp-5 acts as an adhesive primer, overcoming repulsive hydration forces by displacing surface-bound water and generating strong surface adhesion. (
  • Complex stability and conformation of bound substrate protein. (
  • The presence of bound substrate protein increases the thermostability of hsp70 molecular chaperones (heat shock proteins of molecular mass 70 kDa). (
  • Circular dichroism and fluorescence studies of the complex between DnaK and a thermally unstable mutant of staphylococcal nuclease indicate that the bound substrate protein is significantly unfolded. (
  • Alternative in silico approaches assess protein motions through the protein residue network or dynamical correlations from MD simulations. (
  • When operating on a moderately diverse ensemble of models, the conformation ensemble approach is an effective means to identify medium and long range residue-residue contacts. (
  • Given the importance and applicability of protein contacts, considerable effort has been put forth to develop methods which can predict protein residue-residue contacts. (
  • C.d. and fluorescence studies showed that rupture of this disulphide bond changed the protein conformation, which was reflected in partial loss of helical structure and in a greater exposure to the solvent of at least one tryptophan residue. (
  • One typical effect of such inclusions, the lowering of the thermal stability of proteins will be introduced in this mini review. (
  • Conformation analysis using HYDFIT (which globally combines sedimentation and viscosity data), "Conformation Zoning" and Wales-van Holde approaches showed a high degree of flexibility - at least as great as the unconjugated polysaccharides, and very different from the tetanus toxoid (TT) protein used for the conjugation. (
  • The quantification of protein flexibility is based on various methods such as Root Mean Square Fluctuations (RMSF) that rely on multiple MD snapshots or Normal Mode Analysis (NMA) that rely on a single structure and focus on quantifying large movements. (
  • The SAXS experiments revealed however, that PDZK1 has a relatively defined L-shaped conformation with only moderate flexibility. (
  • Glycine takes on a special position, as it has the smallest side chain, only one hydrogen atom, and therefore can increase the local flexibility in the protein structure. (
  • The binding of bis-ANS to multimeric VWF, but not dimeric VWF or control protein bovine serum albumin, was enhanced upon fluid shear application. (
  • We show that a novel retinal specific RGS-motif protein specifically binds to an intermediate conformation involved in GTP hydrolysis by transducin and accelerates phosphate release and the recycling of transducin. (
  • To better understand the robust role this high-energy species plays in folding, we set out to trap the transient intermediate of RNase H at equilibrium by selectively destabilizing the region of the protein known to be unfolded in this species. (
  • Although proteins are essential for splicing, they may not be directly involved in catalysis. (
  • Therefore, it is hypothesized that Prp8 may catalyze splicing either by directly participating in catalysis or by stabilizing the conformation of the catalytically active spliceosome. (
  • In an example application we modeled the process of complex assembly between two proteins: Troponin C (TnC) and the N-terminal helix of Troponin I (TnI N-helix), which occurs in vivo during muscle contraction. (