Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Molecular Sequence Data: 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.Protein Binding: 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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Amino Acid Sequence: 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.Promoter Regions, Genetic: DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.Binding, Competitive: 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.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Kinetics: The rate dynamics in chemical or physical systems.DNA-Binding Proteins: Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.Protein Conformation: 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).Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Protein Structure, Tertiary: 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.Transcription, Genetic: The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Ligands: 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)Mutation: 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.DNA: 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).Structure-Activity Relationship: 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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Escherichia coli: 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.Binding Sites, Antibody: Local surface sites on antibodies which react with antigen determinant sites on antigens (EPITOPES.) They are formed from parts of the variable regions of FAB FRAGMENTS.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.Enhancer Elements, Genetic: Cis-acting DNA sequences which can increase transcription of genes. Enhancers can usually function in either orientation and at various distances from a promoter.Consensus Sequence: A theoretical representative nucleotide or amino acid sequence in which each nucleotide or amino acid is the one which occurs most frequently at that site in the different sequences which occur in nature. The phrase also refers to an actual sequence which approximates the theoretical consensus. A known CONSERVED SEQUENCE set is represented by a consensus sequence. Commonly observed supersecondary protein structures (AMINO ACID MOTIFS) are often formed by conserved sequences.Sequence Homology, Amino Acid: The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.Sp1 Transcription Factor: Promoter-specific RNA polymerase II transcription factor that binds to the GC box, one of the upstream promoter elements, in mammalian cells. The binding of Sp1 is necessary for the initiation of transcription in the promoters of a variety of cellular and viral GENES.Regulatory Sequences, Nucleic Acid: Nucleic acid sequences involved in regulating the expression of genes.Sequence Alignment: 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.DNA Footprinting: A method for determining the sequence specificity of DNA-binding proteins. DNA footprinting utilizes a DNA damaging agent (either a chemical reagent or a nuclease) which cleaves DNA at every base pair. DNA cleavage is inhibited where the ligand binds to DNA. (from Rieger et al., Glossary of Genetics: Classical and Molecular, 5th ed)Transfection: The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.Radioligand Assay: Quantitative determination of receptor (binding) proteins in body fluids or tissue using radioactively labeled binding reagents (e.g., antibodies, intracellular receptors, plasma binders).Recombinant Fusion Proteins: 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.Nuclear Proteins: Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.Bacterial Proteins: Proteins found in any species of bacterium.Cloning, Molecular: 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.Repressor Proteins: Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.Conserved Sequence: 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.Transcriptional Activation: Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Protein Structure, Secondary: 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.Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Nucleic Acid Conformation: The spatial arrangement of the atoms of a nucleic acid or polynucleotide that results in its characteristic 3-dimensional shape.Cattle: 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.Affinity Labels: Analogs of those substrates or compounds which bind naturally at the active sites of proteins, enzymes, antibodies, steroids, or physiological receptors. These analogs form a stable covalent bond at the binding site, thereby acting as inhibitors of the proteins or steroids.Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Chromatin Immunoprecipitation: A technique for identifying specific DNA sequences that are bound, in vivo, to proteins of interest. It involves formaldehyde fixation of CHROMATIN to crosslink the DNA-BINDING PROTEINS to the DNA. After shearing the DNA into small fragments, specific DNA-protein complexes are isolated by immunoprecipitation with protein-specific ANTIBODIES. Then, the DNA isolated from the complex can be identified by PCR amplification and sequencing.Receptors, Cell Surface: Cell surface proteins that bind signalling molecules external to the cell with high affinity and convert this extracellular event into one or more intracellular signals that alter the behavior of the target cell (From Alberts, Molecular Biology of the Cell, 2nd ed, pp693-5). Cell surface receptors, unlike enzymes, do not chemically alter their ligands.Deoxyribonuclease I: An enzyme capable of hydrolyzing highly polymerized DNA by splitting phosphodiester linkages, preferentially adjacent to a pyrimidine nucleotide. This catalyzes endonucleolytic cleavage of DNA yielding 5'-phosphodi- and oligonucleotide end-products. The enzyme has a preference for double-stranded DNA.Trans-Activators: Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.RNA, Messenger: RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.Cells, Cultured: Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.Electrophoretic Mobility Shift Assay: An electrophoretic technique for assaying the binding of one compound to another. Typically one compound is labeled to follow its mobility during electrophoresis. If the labeled compound is bound by the other compound, then the mobility of the labeled compound through the electrophoretic medium will be retarded.Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.Amino Acid Motifs: 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.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.DNA Primers: 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.Calcium: 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.Macromolecular Substances: 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.Genes, Reporter: Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.HeLa Cells: The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.Regulatory Elements, Transcriptional: Nucleotide sequences of a gene that are involved in the regulation of GENETIC TRANSCRIPTION.Sequence Homology, Nucleic Acid: The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.Autoradiography: The making of a radiograph of an object or tissue by recording on a photographic plate the radiation emitted by radioactive material within the object. (Dorland, 27th ed)Oligodeoxyribonucleotides: 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.Proteins: 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.Sequence Deletion: Deletion of sequences of nucleic acids from the genetic material of an individual.Spectrometry, Fluorescence: Measurement of the intensity and quality of fluorescence.Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer.Allosteric Regulation: 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.Amino Acid Substitution: 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.Iodine Radioisotopes: Unstable isotopes of iodine that decay or disintegrate emitting radiation. I atoms with atomic weights 117-139, except I 127, are radioactive iodine isotopes.Magnesium: 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.Tumor Cells, Cultured: Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.Response Elements: Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promoter and enhancer regions.Peptides: 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.Rabbits: 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.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Adenosine Triphosphate: 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.Molecular Structure: 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.Models, Chemical: Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.Allosteric Site: 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.Hydrogen-Ion Concentration: 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)Nucleotide Motifs: Commonly observed BASE SEQUENCE or nucleotide structural components which can be represented by a CONSENSUS SEQUENCE or a SEQUENCE LOGO.Models, Biological: 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.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Thermodynamics: 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)Photoaffinity Labels: Biologically active molecules which are covalently bound to the enzymes or binding proteins normally acting on them. Binding occurs due to activation of the label by ultraviolet light. These labels are used primarily to identify binding sites on proteins.Saccharomyces cerevisiae: 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.Point Mutation: 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.Cross-Linking Reagents: 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.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.Restriction Mapping: Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.Escherichia coli Proteins: Proteins obtained from ESCHERICHIA COLI.Magnetic Resonance Spectroscopy: 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).Computational Biology: 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.Molecular Weight: The sum of the weight of all the atoms in a molecule.Dose-Response Relationship, Drug: The relationship between the dose of an administered drug and the response of the organism to the drug.Membrane Proteins: 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.Algorithms: A procedure consisting of a sequence of algebraic formulas and/or logical steps to calculate or determine a given task.Receptors, Nicotinic: One of the two major classes of cholinergic receptors. Nicotinic receptors were originally distinguished by their preference for NICOTINE over MUSCARINE. They are generally divided into muscle-type and neuronal-type (previously ganglionic) based on pharmacology, and subunit composition of the receptors.Zinc: 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.Antibodies, Monoclonal: Antibodies produced by a single clone of cells.Homeodomain Proteins: Proteins encoded by homeobox genes (GENES, HOMEOBOX) that exhibit structural similarity to certain prokaryotic and eukaryotic DNA-binding proteins. Homeodomain proteins are involved in the control of gene expression during morphogenesis and development (GENE EXPRESSION REGULATION, DEVELOPMENTAL).Chickens: 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.Gene Expression Regulation, Bacterial: Any of the processes by which cytoplasmic or intercellular factors influence the differential control of gene action in bacteria.Luciferases: Enzymes that oxidize certain LUMINESCENT AGENTS to emit light (PHYSICAL LUMINESCENCE). The luciferases from different organisms have evolved differently so have different structures and substrates.TritiumCell Nucleus: Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)Signal Transduction: The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.Molecular Docking Simulation: 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.Surface Plasmon Resonance: A biosensing technique in which biomolecules capable of binding to specific analytes or ligands are first immobilized on one side of a metallic film. Light is then focused on the opposite side of the film to excite the surface plasmons, that is, the oscillations of free electrons propagating along the film's surface. The refractive index of light reflecting off this surface is measured. When the immobilized biomolecules are bound by their ligands, an alteration in surface plasmons on the opposite side of the film is created which is directly proportional to the change in bound, or adsorbed, mass. Binding is measured by changes in the refractive index. The technique is used to study biomolecular interactions, such as antigen-antibody binding.Models, Genetic: Theoretical representations that simulate the behavior or activity of genetic processes or phenomena. They include the use of mathematical equations, computers, and other electronic equipment.Azides: Organic or inorganic compounds that contain the -N3 group.COS Cells: CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)Transcription Initiation Site: The first nucleotide of a transcribed DNA sequence where RNA polymerase (DNA-DIRECTED RNA POLYMERASE) begins synthesizing the RNA transcript.Cations, Divalent: Positively charged atoms, radicals or groups of atoms with a valence of plus 2, which travel to the cathode or negative pole during electrolysis.CHO Cells: CELL LINE derived from the ovary of the Chinese hamster, Cricetulus griseus (CRICETULUS). The species is a favorite for cytogenetic studies because of its small chromosome number. The cell line has provided model systems for the study of genetic alterations in cultured mammalian cells.NFI Transcription Factors: Transcription factors that were originally identified as site-specific DNA-binding proteins essential for DNA REPLICATION by ADENOVIRUSES. They play important roles in MAMMARY GLAND function and development.Molecular Conformation: The characteristic three-dimensional shape of a molecule.Circular Dichroism: 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)Chloramphenicol O-Acetyltransferase: An enzyme that catalyzes the acetylation of chloramphenicol to yield chloramphenicol 3-acetate. Since chloramphenicol 3-acetate does not bind to bacterial ribosomes and is not an inhibitor of peptidyltransferase, the enzyme is responsible for the naturally occurring chloramphenicol resistance in bacteria. The enzyme, for which variants are known, is found in both gram-negative and gram-positive bacteria. EC 2.3.1.28.Receptors, Neurotransmitter: Cell surface receptors that bind signalling molecules released by neurons and convert these signals into intracellular changes influencing the behavior of cells. Neurotransmitter is used here in its most general sense, including not only messengers that act to regulate ion channels, but also those which act on second messenger systems and those which may act at a distance from their release sites. Included are receptors for neuromodulators, neuroregulators, neuromediators, and neurohumors, whether or not located at synapses.Receptors, Drug: Proteins that bind specific drugs with high affinity and trigger intracellular changes influencing the behavior of cells. Drug receptors are generally thought to be receptors for some endogenous substance not otherwise specified.Zinc Fingers: Motifs in DNA- and RNA-binding proteins whose amino acids are folded into a single structural unit around a zinc atom. In the classic zinc finger, one zinc atom is bound to two cysteines and two histidines. In between the cysteines and histidines are 12 residues which form a DNA binding fingertip. By variations in the composition of the sequences in the fingertip and the number and spacing of tandem repeats of the motif, zinc fingers can form a large number of different sequence specific binding sites.RNA-Binding Proteins: Proteins that bind to RNA molecules. Included here are RIBONUCLEOPROTEINS and other proteins whose function is to bind specifically to RNA.YY1 Transcription Factor: A ubiquitously expressed zinc finger-containing protein that acts both as a repressor and activator of transcription. It interacts with key regulatory proteins such as TATA-BINDING PROTEIN; TFIIB; and ADENOVIRUS E1A PROTEINS.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Xenopus laevis: The commonest and widest ranging species of the clawed "frog" (Xenopus) in Africa. This species is used extensively in research. There is now a significant population in California derived from escaped laboratory animals.Chromatography, Affinity: A chromatographic technique that utilizes the ability of biological molecules to bind to certain ligands specifically and reversibly. It is used in protein biochemistry. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Hydrogen Bonding: 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.Structural Homology, Protein: 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.Temperature: 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.DNA, Complementary: Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.Membranes: Thin layers of tissue which cover parts of the body, separate adjacent cavities, or connect adjacent structures.Epitopes: Sites on an antigen that interact with specific antibodies.Trypsin: 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 3.4.21.4.Oligonucleotides: Polymers made up of a few (2-20) nucleotides. In molecular genetics, they refer to a short sequence synthesized to match a region where a mutation is known to occur, and then used as a probe (OLIGONUCLEOTIDE PROBES). (Dorland, 28th ed)CCAAT-Enhancer-Binding Proteins: A class of proteins that were originally identified by their ability to bind the DNA sequence CCAAT. The typical CCAAT-enhancer binding protein forms dimers and consists of an activation domain, a DNA-binding basic region, and a leucine-rich dimerization domain (LEUCINE ZIPPERS). CCAAT-BINDING FACTOR is structurally distinct type of CCAAT-enhancer binding protein consisting of a trimer of three different subunits.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.TATA Box: A conserved A-T rich sequence which is contained in promoters for RNA polymerase II. The segment is seven base pairs long and the nucleotides most commonly found are TATAAAA.Saccharomyces cerevisiae Proteins: 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.Cysteine: A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.Nuclear Magnetic Resonance, Biomolecular: 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.Protein Structure, Quaternary: The characteristic 3-dimensional shape and arrangement of multimeric proteins (aggregates of more than one polypeptide chain).Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.Proto-Oncogene Proteins c-ets: A family of transcription factors that share a unique DNA-binding domain. The name derives from viral oncogene-derived protein oncogene protein v-ets of the AVIAN ERYTHROBLASTOSIS VIRUS.Lysine: An essential amino acid. It is often added to animal feed.Rats, Inbred Strains: Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.Software: Sequential operating programs and data which instruct the functioning of a digital computer.Introns: Sequences of DNA in the genes that are located between the EXONS. They are transcribed along with the exons but are removed from the primary gene transcript by RNA SPLICING to leave mature RNA. Some introns code for separate genes.Computer Simulation: Computer-based representation of physical systems and phenomena such as chemical processes.Repetitive Sequences, Nucleic Acid: Sequences of DNA or RNA that occur in multiple copies. There are several types: INTERSPERSED REPETITIVE SEQUENCES are copies of transposable elements (DNA TRANSPOSABLE ELEMENTS or RETROELEMENTS) dispersed throughout the genome. TERMINAL REPEAT SEQUENCES flank both ends of another sequence, for example, the long terminal repeats (LTRs) on RETROVIRUSES. Variations may be direct repeats, those occurring in the same direction, or inverted repeats, those opposite to each other in direction. TANDEM REPEAT SEQUENCES are copies which lie adjacent to each other, direct or inverted (INVERTED REPEAT SEQUENCES).Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Protein Subunits: 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.Calorimetry: 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)Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.RNA: 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)Tryptophan: 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.Drosophila Proteins: Proteins that originate from insect species belonging to the genus DROSOPHILA. The proteins from the most intensely studied species of Drosophila, DROSOPHILA MELANOGASTER, are the subject of much interest in the area of MORPHOGENESIS and development.Lectins: Proteins that share the common characteristic of binding to carbohydrates. Some ANTIBODIES and carbohydrate-metabolizing proteins (ENZYMES) also bind to carbohydrates, however they are not considered lectins. PLANT LECTINS are carbohydrate-binding proteins that have been primarily identified by their hemagglutinating activity (HEMAGGLUTININS). However, a variety of lectins occur in animal species where they serve diverse array of functions through specific carbohydrate recognition.PhotochemistryTorpedo: A genus of the Torpedinidae family consisting of several species. Members of this family have powerful electric organs and are commonly called electric rays.Nucleotides: 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)Time Factors: Elements of limited time intervals, contributing to particular results or situations.Bungarotoxins: Neurotoxic proteins from the venom of the banded or Formosan krait (Bungarus multicinctus, an elapid snake). alpha-Bungarotoxin blocks nicotinic acetylcholine receptors and has been used to isolate and study them; beta- and gamma-bungarotoxins act presynaptically causing acetylcholine release and depletion. Both alpha and beta forms have been characterized, the alpha being similar to the large, long or Type II neurotoxins from other elapid venoms.Protein Interaction Domains and Motifs: 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.Species Specificity: The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.Protein Interaction Mapping: Methods for determining interaction between PROTEINS.Oligonucleotide Probes: Synthetic or natural oligonucleotides used in hybridization studies in order to identify and study specific nucleic acid fragments, e.g., DNA segments near or within a specific gene locus or gene. The probe hybridizes with a specific mRNA, if present. Conventional techniques used for testing for the hybridization product include dot blot assays, Southern blot assays, and DNA:RNA hybrid-specific antibody tests. Conventional labels for the probe include the radioisotope labels 32P and 125I and the chemical label biotin.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Proto-Oncogene Proteins: Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.DNA, Viral: Deoxyribonucleic acid that makes up the genetic material of viruses.Cations: Positively charged atoms, radicals or groups of atoms which travel to the cathode or negative pole during electrolysis.Terbium: Terbium. An element of the rare earth family of metals. It has the atomic symbol Tb, atomic number 65, and atomic weight 158.92.Polymerase Chain Reaction: 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.Oligopeptides: Peptides composed of between two and twelve amino acids.Amino Acids: 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.5' Flanking Region: The region of DNA which borders the 5' end of a transcription unit and where a variety of regulatory sequences are located.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.DNA, Bacterial: Deoxyribonucleic acid that makes up the genetic material of bacteria.Fungal Proteins: Proteins found in any species of fungus.Adenosine Diphosphate: Adenosine 5'-(trihydrogen diphosphate). An adenine nucleotide containing two phosphate groups esterified to the sugar moiety at the 5'-position.Position-Specific Scoring Matrices: Tabular numerical representations of sequence motifs displaying their variability as likelihood values for each possible residue at each position in a sequence. Position-specific scoring matrices (PSSMs) are calculated from position frequency matrices.Integration Host Factors: Bacterial proteins that are used by BACTERIOPHAGES to incorporate their DNA into the DNA of the "host" bacteria. They are DNA-binding proteins that function in genetic recombination as well as in transcriptional and translational regulation.Transcription Factor AP-2: A family of DNA binding proteins that regulate expression of a variety of GENES during CELL DIFFERENTIATION and APOPTOSIS. Family members contain a highly conserved carboxy-terminal basic HELIX-TURN-HELIX MOTIF involved in dimerization and sequence-specific DNA binding.3T3 Cells: Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.Peptide Mapping: Analysis of PEPTIDES that are generated from the digestion or fragmentation of a protein or mixture of PROTEINS, by ELECTROPHORESIS; CHROMATOGRAPHY; or MASS SPECTROMETRY. The resulting peptide fingerprints are analyzed for a variety of purposes including the identification of the proteins in a sample, GENETIC POLYMORPHISMS, patterns of gene expression, and patterns diagnostic for diseases.Drosophila: A genus of small, two-winged flies containing approximately 900 described species. These organisms are the most extensively studied of all genera from the standpoint of genetics and cytology.Oocytes: Female germ cells derived from OOGONIA and termed OOCYTES when they enter MEIOSIS. The primary oocytes begin meiosis but are arrested at the diplotene state until OVULATION at PUBERTY to give rise to haploid secondary oocytes or ova (OVUM).HEK293 Cells: A cell line generated from human embryonic kidney cells that were transformed with human adenovirus type 5.Gene Expression Regulation, Viral: Any of the processes by which cytoplasmic factors influence the differential control of gene action in viruses.3' Untranslated Regions: The sequence at the 3' end of messenger RNA that does not code for product. This region contains transcription and translation regulating sequences.Operon: In bacteria, a group of metabolically related genes, with a common promoter, whose transcription into a single polycistronic MESSENGER RNA is under the control of an OPERATOR REGION.Muscles: Contractile tissue that produces movement in animals.Exons: The parts of a transcript of a split GENE remaining after the INTRONS are removed. They are spliced together to become a MESSENGER RNA or other functional RNA.

Extra-vesicular binding of noradrenaline and guanethidine in the adrenergic neurones of the rat heart: a proposed site of action of adrenergic neurone blocking agents. (1/81452)

1 The binding and efflux characteristics of [14C]-guanethidine and [3H]-noradrenaline were studied in heart slices from rats which were pretreated with reserpine and nialamide. 2 Binding of both compounds occurred at extra-vesicular sites within the adrenergic neurone. After a brief period of rapid washout, the efflux of [14C]-guanethidine and [3H]-noradrenaline proceeded at a steady rate. The efflux of both compounds appeared to occur from a single intraneuronal compartment. 3 (+)-Amphetamine accelerated the efflux of [14C]-noradrenaline; this effect was inhibited by desipramine. 4 Unlabelled guanethidine and amantadine also increased the efflux of labelled compounds. Cocaine in high concentrations increased slightly the efflux of [14C]-guanethidine but not that of [3H]-noradrenaline. 5 Heart slices labelled with [3H]-noradrenaline became refractory to successive exposures to releasing agents although an appreciable amount of labelled compound was still present in in these slices. 6 It is suggested that [14C]-guanethidine and [3H]-noradrenaline are bound at a common extravesicular site within the adrenergic neurone. Binding of guanethidine to the extra-vesicular site may be relevant to its pharmacological action, i.e., the blockade of adrenergic transmission.  (+info)

The bioavailability, dispostion kinetics and dosage of sulphadimethoxine in dogs. (2/81452)

The disposition kinetics of sulphadimethoxine were studied in six normal beagle dogs after intravenous injection of a single dose (55 mg/kg). The median (range) distribution and elimination half times of the drug were 2.36 (2.06-3.35) hours and 13.10 (9.71-16.50) hours, respectively. Total body clearance of the drug had a median value of 21.7 ml/kg/h and a mean value of 21.4 ml/kg/h. While the overall tissue to plasma level ratio (k12/k21) of the drug was 0.55 after distribution equilibrium had been attained, analogue computer simulated curves showed that at 24 hours the fractions (percentage) of the dose in the central and tissue compartments were 12 and 11%, respectively. The drug was shown, by equilibrium dialysis method, to be highly bound to plasma proteins (greater than 75%) within the usual therapeutic range (50 to 150 mug/ml) of plasma levels. The systemic availability of sulphadimethoxine from the oral suspension was 32.8% (22.5-80.0). Since the absorption half time, 1.87 (0.86-3.22) hours, was considerably shorter than the half-life, 13.10 (9.71-16.50) hours, of the drug, the rate of absorption would have little influence on the dosage regimen. Based on the experimental data obtained, a satisfactory dosage regimen might consist of a priming dose of 55 mg/kg by the intravenous route and maintenance doses of either 27.5 mg/kg of sulphadimethoxine injection given intravenously or 55 mg/kg of the oral suspension administered at 24 hour intervals. The adequacy and duration of therapy will depend upon the clinical response obtained.  (+info)

Specific receptors for glucocorticoid in the cytoplasm of the liver of AH 130 tumor-bearing rats. (3/81452)

Specific receptors for dexamethasone (11beta, 17alpha, 21-trihydroxy-9alpha-fluoro-16alpha-methyl-1,4-pregnadiene-3,20-dione) in the cytoplasm of the liver from AH 130 (solid type) tumor-bearing rats markedly increased in the advanced stage of tumor growth. The cytoplasmic receptors of the livers of normal and tumor-bearing rats differed in their affinities for dexamethasone, and their apparent equilibrium (dissociation) constants (K) for dexamethasone were 4.0 and 2.6 X 10(-9) M, respectively. The rates of dissociation of dexamethasone-receptor complexes and the heat denaturations of the receptors in the livers of normal and tumor-bearing rats were similar. The glucocorticoid receptors of tumor-bearing rat liver had slightly higher affinities than did those of normal liver for all the steroids tested. Only a trace amount of receptors for dexamethasone could be detected in the cytoplasm of AH 130 ascites cells.  (+info)

The interaction of rhodium(II) carboxylates with enzymes. (4/81452)

The effect of rhodium(II) acetate, propionate, and methoxyacetate on the activity of 17 enzymes was evaluated. The enzymes were preincubated with the rhodium(II) complexes in order to detect irreversible inhibition. All enzymes that have essential sulfhydryl groups in or near their active site were found to be irreversibly inhibited. Those enzymes without essential sulfhydryl groups were not affected. In each case, the rate of inactivation closely paralleled the observed toxicity and antitumor activity of rhodium(II) carboxylates; that is, rhodium(II) propionate greater than rhodium(II) acetate greater than rhodium(II) methoxyacetate. In addition, those enzymes that have been demonstrated to be most sensitive to established sulfhydryl inhibitors, such as glyceraldehyde-3-phosphate dehydrogenase, were also most sensitive to rhodium(II) carboxylate inactivation. Proton nuclear magnetic resonance measurements made during the titration of rhodium(II) acetate with cysteine showed that breakdown of the carboxylate cage occurred as a result of reaction with this sulfhydryl-containing amino acid.  (+info)

The direct spectrophotometric observation of benzo(a)pyrene phenol formation by liver microsomes. (5/81452)

Optical spectral repetitive scan analysis during the oxidative metabolism of benzo(a)pyrene by liver microsomal suspensions reveals the time-dependent formation of an intermediate(s) of which the visible spectra resemble those of several benzo(a)pyrene phenols. Liver microsomes from 3-methylcholanthrene-treated rats showed a greater rate of formation of the phenols than did microsomes from control animals; the rate of formation catalyzed by liver microsomes from phenobarbital-pretreated rats was intermediate. When 3-hydroxybenzo(a)pyrene was used as a standard for comparison of activity, the rates of formation of phenols were compared when measured by fluorometric, spectrophotometric, or high-pressure liquid chromatographic analytical techniques. An epoxide hydrase inhibitor, 1,1,1-trichloropropene-2,3-oxide, enhanced phenol formation regardless of the source of liver microsomes, and 7,8-benzoflavone inhibited control and 3-methylcholanthrene-induced microsomal metabolism of benzo(a)pyrene, 7,8-Benzoflavone did not effect benzo(a)pyrene metabolism by liver microsomes from phenobarbital-pretreated rats. The effect of inhibitors on the spectrophotometric assay correlates well with the results obtained from benzo(a)pyrene metabolite analysis using high-pressure liquid chromatography.  (+info)

Differences in benzo(a)pyrene metabolism between rodent liver microsomes and embryonic cells. (6/81452)

Differences in benzo(a)pyrene metabolite pattern have been shown by rodent liver microsomes (Sprague-Dawley) and rodent embryo cells from Syrian hamsters and NIH Swiss mice. Rodent liver induced by methylcholanthrene shows marked quantitative variation between species. Additional pattern changes were found in mouse and hamster embryo secondary cultures with a reduction of the K-region metabolites and a marked increase in 9-hydroxybenzo(a)-pyrene. These results are indicative of a region-specific attack on the carcinogen by the cell monooxygenases which is distinct from the liver attack of microsomal enzymes on benzo(a)pyrene. These results suggest that activation and detoxification of benzo(a)pyrene may be species and tissue variable, and susceptibility and resistence to malignant transformation may be predicted on induction of a fortuitous combination of intermediate metabolic steps.  (+info)

Action of partially thiolated polynucleotides on the DNA polymerase alpha from regenerating rat liver. (7/81452)

The effects of partially thiolated polynucleotides on the DNA polymerase alpha from regenerating rat liver were investigated. The enzyme was isolated from the nuclear fraction essentially according to the method of Baril et al.; it was characterized as the alpha polymerase on the basis of its response to synthetic templates and its inhibition with N-ethylmaleimide. Although polycytidylic acid had no effect on the DNA polymerase alpha either as a template or as an inhibitor, partially thiolated polycytidylic acid (MPC) was found to be a potent inhibitor, its activity being directly related to its extent of thiolation (percentage of 5-mercaptocytidylate units in the polymer). In comparison, the DNA polymerase beta which was purified from normal rat liver nuclear fraction, was much less sensitive to inhibition by MPC. Analysis of the inhibition of the alpha polymerase by the method of Lineweaver and Burk showed that the inhibitory action of MPC was competitively reversible with the DNA template, but the binding of the 7.2%-thiolated MPC to the enzyme was much stronger than that of the template (Ki/Km less than 0.03). Polyuridylic acid as such showed some inhibitory activity which increased on partial thiolation, but the 8.4%-thiolated polyuridylic acid was less active than the 7.2% MPC. When MPC was annealed with polyinosinic acid, it lost 80% of its inhibitory activity in the double-stranded configuration. However, 1 to 2%-thiolated DNA isolates were significantly more potent inhibitors than were comparable (1.2%-thiolated) MPC and showed competitive reversibility with the unmodified (but "activated") DNA template. These results indicate that the inhibitory activities of partially thiolated polynucleotides depend not only on the percentage of 5-mercapto groups but also on the configuration, base composition, and other specific structural properties.  (+info)

The effects of estrogens and antiestrogens on hormone-responsive human breast cancer in long-term tissue culture. (8/81452)

We have established or characterized six lines of human breast cancer maintained in long-term tissue culture for at least 1 year and have examined these lines for estrogen responsiveness. One of these cell lines, MCF-7, shows marked stimulation of macromolecular synthesis and cell division with physiological concentrations of estradiol. Antiestrogens are strongly inhibitory, and at concentrations greater than 3 X 10(-7) M they kill cells. Antiestrogen effects are prevented by simultaneous treatment with estradiol or reversed by addition of estradiol to cells incubated in antiestrogen. Responsive cell lines contain high-affinity specific estradiol receptors. Antiestrogens compete with estradiol for these receptors but have a lower apparent affinity for the receptor than estrogens. Stimulation of cells by estrogens is biphasic, with inhibition and cell death at concentrations of 17beta-estradiol or diethylstilbestrol exceeding 10(-7) M. Killing by high concentrations of estrogen is probably a nonspecific effect in that we observe this response with 17alpha-estradiol at equivalent concentrations and in the otherwise unresponsive cells that contain no estrogen receptor sites.  (+info)

*Ligand binding assay

... and it is possible that there is more than one specific binding site for one ligand. Non specific binding refers to the binding ... binding-assay.com/binding-assay-types/solid-phase-assays/on-bead-assays Moss, ed. by Tom (2001). "Filter-Binding Assays". DNA- ... If the ligand were to have bound to multiple sites that have differing radioligand affinities, then the Scatchard plot would ... Ligand binding assays (LBA) is an assay, or an analytic procedure, whose procedure or method relies on the binding of ligand ...

*Protein primary structure

This is used to strengthen the binding to "hard" metal ions such as calcium. ADP-ribosylation The large ADP-ribosyl group can ... As with phosphorylation, sulfation adds a negative charge to a previously neutral site. prenylation and palmitoylation − C ( = ... The phosphorylated tyrosines are often used as "handles" by which proteins can bind to one another, whereas phosphorylation of ... Functionally, however, the acetylation of lysine residues is used to regulate the binding of proteins to nucleic acids. The ...

*Binding site

When more than one type of ligand can bind to a binding site, competition ensues. Binding sites also exhibit chemical ... Binding sites on proteins can sometimes recognize other proteins. When a binding site of one protein identifies with another ... A more specific type of binding site is the transcription factor binding site present on DNA. Short, recurring patterns in DNA ... Binding sites also exist on antibodies as specifically coded regions that bind antigens based upon their structure. Several ...

*DNA binding site

DNA binding sites are a type of binding site found in DNA where other molecules may bind. DNA binding sites are distinct from ... The sum of DNA binding sites of a specific transcription factor is referred to as its cistrome. DNA binding sites also ... It has been reported that some binding sites have potential to undergo fast evolutionary change. DNA binding sites can be ... Thus, we can distinguish between transcription factor-binding sites, restriction sites and recombination sites. Some authors ...

*NTP binding site

... binding sites, it interacts with the bound nucleotide's phosphoryl groups. For the binding site to be able to bind a nucleotide ... An NTP binding site is a type of binding site found in nucleoside monophosphate (NMP) kinases, N can be adenosine or guanosine ... the nucleotide must be complex bound to Mg2+ or Mn2+. Nucleotide binding will cause conformational changes in the protein ...

*Primer binding site

A PCR primer binding site is a site where a polymerase chain reaction (PCR) primer binds, to prime duplication of a complement ... A primer binding site is a region of a nucleotide sequence where an RNA or DNA single-stranded primer binds to start ... The HIV primer binding site is a structured RNA element in the genomes of retroviruses to which tRNA binds to initiate reverse ... The primer binding site is on one of the two complementary strands of a double-stranded nucleotide polymer, in the strand which ...

*PyrR binding site

The PyrR binding site is an RNA element that is found upstream of a variety of genes involved in pyrimidine biosynthesis and ... When the protein binds, a downstream terminator hairpin forms, repressing transcription of biosynthesis genes. Bonner, ER; ... The RNA structure permits binding of PyrR protein which regulates pyrimidine biosynthesis in Bacillus subtilis. ... Page for PyrR binding site at Rfam. ...

*Ribosome-binding site

A ribosome binding site, or ribosomal binding site, (RBS) is a sequence of nucleotides upstream of the start codon of an mRNA ... "Ribosomal Binding Site Sequence Requirements". www.thermofisher.com. Retrieved 2015-10-16. "Help:Ribosome Binding Site - parts. ... it is not considered a ribosome binding site. Eukaryotic ribosomes are known to bind to transcripts in a mechanism unlike the ... "Ribosome binding site recognition using neural networks". Genetics and Molecular Biology. 27 (4): 644-650. doi:10.1590/S1415- ...

*AP-1 Binding Site

The AP-1 binding site, also known as the AP-1 promoter site, is a DNA nucleotide sequence to which AP-1 transcription factors ... The AP-1 binding site, in humans, has a nucleotide sequence of ATGAGTCAT. AP-1 Nucleotide Sequence. ...

*Alpha operon ribosome binding site

The alpha operon ribosome binding site in bacteria is surrounded by this complex pseudoknotted RNA structure. Translation of ... Page for Alpha operon ribosome binding site at Rfam. ... acts as a translational repressor by binding to the nested ...

*Transcription factor binding site databases

The application of ChIP-seq methods has reliably discovered transcription factor binding sites and histone modification sites. ... Comprehensive List of transcription factor binding sites (TFBSs) databases based on ChIP-seq data as follows: Park, Peter J. (1 ... Ziebarth, Jesse D.; Bhattacharya, Anindya; Cui, Yan (1 January 2013). "CTCFBSDB 2.0: a database for CTCF-binding sites and ... update of the open-access database of transcription factor binding profiles and its web framework". Nucleic Acids Research. doi ...

*Rous sarcoma virus (RSV) primer binding site (PBS)

This family represents a structured region around the Rous sarcoma virus (RSV) primer binding site (PBS). This region is known ... Page for Rous sarcoma virus (RSV) primer binding site (PBS) at Rfam. ...

*Membrane-bound transcription factor site-2 protease

... , or site-2 protease (S2P) for short, is an enzyme (EC 3.4.24.85) encoded by ... Membrane-bound transcription factor site-1 protease Brown MS, Goldstein JL (1999). "A proteolytic pathway that controls the ... SREBP site 2 protease at the US National Library of Medicine Medical Subject Headings (MeSH) S2P endopeptidase at the US ... Known substrates include sterol regulatory element-binding protein (SREBP)-1, SREBP-2 and forms of the transcriptional ...

*Membrane-bound transcription factor site-1 protease

... , or site-1 protease (S1P) for short, also known as subtilisin/kexin-isozyme ... Membrane-bound transcription factor site-2 protease GRCh38: Ensembl release 89: ENSG00000140943 - Ensembl, May 2017 GRCm38: ... Membrane-bound transcription factor peptidase, site 1". Brown MS, Goldstein JL (1999). "A proteolytic pathway that controls the ... site-1 protease at the US National Library of Medicine Medical Subject Headings (MeSH) This article incorporates text from the ...

*6-Diazo-5-oxo-L-norleucine

Pinkus LM (1977). "Glutamine binding sites". Meth. Enzymol. Methods in Enzymology. 46: 414-27. doi:10.1016/S0076-6879(77)46049- ... Due to its similarity to glutamine it can enter catalytic centres of these enzymes and inhibits them by covalent binding, or ...

*CCDC82

"Transcription Factor Binding Sites". ElDorado. Genomatix. "SAPS". Biology Workbench. SDSU. [permanent dead link] "Large-scale ... CCDC82 has several predicted phosphorylation sites. There are 32 predicted serine phosphorylation sites, 5 threonine, and 3 ... Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (November 2006). "Global, in vivo, and site-specific ...

*C7orf43

... including binding sites for zinc fingers and Kruppel-like transcription factors. The top 20 transcription binding sites as ... "C7orf43-promoter binding sites". Genomatix. Retrieved 5 April 2015. "Uncharacterized protein C7orf43 [Homo sapiens]". NCBI ... C7orf43 has three phosphorylated sites, Ser 517, Thr 541 and, Ser 546. All three sites are relatively well-conserved throughout ... There are several transcription factor binding sites located in this promoter, ...

*Anti-dsDNA antibodies

Birmingham: Binding Site. ISBN 0-7044-2437-1. Slater NG, Cameron JS, Lessof MH (September 1976). "The Crithidia luciliae ... Serum is incubated with the beads and in the presence of anti-dsDNA antibodies, or any other ANA, the antibodies will bind and ... If anti-dsDNA antibodies are present, incubation of serum and the microarray allow for binding and the dots can then be ... Upon incubation with serum containing anti-dsDNA antibodies, the antibodies will bind to the DNA and can then be visualised ...

*M. Vijayan

Madhusudan; Vijayan, M. (July 1992). "Additional binding sites in lysozyme. X-ray analysis of lysozyme complexes with ... side chain conformation in proteins and additional binding sites in lysozyme. Vijayan has published more than 260 peer reviewed ... M. Vijayan profile on Biomed Experts Mamannamana Vijayan publications list M. Vijayan home page at Indian Institute of Science ... The specific systems studied by him include RecA, RuvA, uracil DNA glycosylase, single stranded DNA binding protein, ribosome ...

*Anti-neutrophil cytoplasmic antibody

Birmingham: The Binding Site. ISBN 0704485109. Savige, J; Davies, D; Falk, RJ; Jennette, JC; Wiik, A (Mar 2000). " ...

*Sequence motif

For example, many DNA binding proteins that have affinity for specific DNA binding sites bind DNA in only its double-helical ... "DNA binding sites: representation and discovery". Bioinformatics. 16 (1): 16-23. doi:10.1093/bioinformatics/16.1.16. PMID ... 34 (Web Server issue): W369-373. doi:10.1093/nar/gkl198. PMC 1538909 . PMID 16845028. Weirauch; et al. (2013). "Evaluation of ... An example is the N-glycosylation site motif: Asn, followed by anything but Pro, followed by either Ser or Thr, followed by ...

*Nitric oxide synthase

The FMN binding domain is homologous to flavodoxins, and the two domain fragment containing the FAD and NADPH binding sites is ... The oxygenase domain is a unique extended beta sheet cage with binding sites for heme and pterin. NOSs can be dimeric, ... Liu Q, Gross SS (1996). "Binding sites of nitric oxide synthases". Meth. Enzymol. 268: 311-24. doi:10.1016/S0076-6879(96)68033- ... which is linked in the middle of the protein to a calmodulin-binding domain. Binding of calmodulin appears to act as a " ...

*Gary Stormo

Stormo, G. D. (1 January 2000). "DNA binding sites: representation and discovery". Bioinformatics. 16 (1): 16-23. doi:10.1093/ ... The first use of PWMs was in the discovery of RNA sites that function as translation initiation sites. The advantages of PWMs ... algorithm to distinguish translational initiation sites in E. coli". Nucleic Acids Research. 10 (9): 2997-3011. doi:10.1093/nar ... work involves analysis of these interactions and developing pattern recognition algorithms to discover regulatory sites in DNA ...

*1-phosphofructokinase

There are two ATP binding sites; a substrate site where the phosphate transfer occurs, and an allosteric site where allosteric ... In addition to the catalytic binding sites, there are 4 additional binding sites for allosteric regulation. 1- ... AMP and ADP are both positive effectors of 1-phosphofructokinase and bind allosterically to activate the reaction. This ... 1-Phosphofructokinase is a tetramer of 4 identical subunits that each have a catalytic site. ...

*Position weight matrix

Erill I, O'Neill MC (2009). "A reexamination of information theory-based methods for DNA-binding site identification". BMC ... The score is greater than 0 if it is more likely to be a functional site than a random site, and less than 0 if it is more ... 2003). "MATCHTM: a tool for searching transcription factor binding sites in DNA sequences". Nucleic Acids Research. 31 (13): ... Stormo, G. D. (1 January 2000). "DNA binding sites: representation and discovery". Bioinformatics. 16 (1): 16-23. doi:10.1093/ ...

*UCKL1

2002). "Epstein-Barr virus encoded nuclear protein EBNA-3 binds a novel human uridine kinase/uracil phosphoribosyltransferase ... 2006). "A probability-based approach for high-throughput protein phosphorylation analysis and site localization". Nat. ...

*Cannabidiolic acid synthase

CBDA synthase has four binding sites; two for FAD and two for the substrate. Cannabidiolic acid synthase catalyses the ... It covalently binds FAD, and does not require coenzymes, molecular oxygen, hydrogen peroxide, or metal ion cofactors for the ...
The gain and loss of functional transcription factor binding sites has been proposed as a major source of evolutionary change in cis-regulatory DNA and gene expression. We have developed an evolutionary model to study binding-site turnover that uses multiple sequence alignments to assess the evolutionary constraint on individual binding sites, and to map gain and loss events along a phylogenetic tree. We apply this model to study the evolutionary dynamics of binding sites of the Drosophila melanogaster transcription factor Zeste, using genome-wide in vivo (ChIP-chip) binding data to identify functional Zeste binding sites, and the genome sequences of D. melanogaster, D. simulans, D. erecta, and D. yakuba to study their evolution. We estimate that more than 5% of functional Zeste binding sites in D. melanogaster were gained along the D. melanogaster lineage or lost along one of the other lineages. We find that Zeste-bound regions have a reduced rate of binding-site loss and an increased rate of binding
TY - GEN. T1 - Identification of over-represented combinations of transcription factor binding sites in sets of co-expressed genes. AU - Huang, Shao-Shan. AU - Fulton, Debra L.. AU - Arenillas, David J.. AU - Perco, Paul. AU - Ho Sui, Shannan J.. AU - Mortimer, James R.. AU - Wasserman, Wyeth W.. PY - 2006/12/1. Y1 - 2006/12/1. N2 - Transcription regulation is mediated by combinatorial interactions between diverse trans-acting proteins and arrays of cis-regulatory sequences. Revealing this complex interplay between transcription factors and binding sites remains a fundamental problem for understanding the flow of genetic information. The oPOSSUM analysis system facilitates the interpretation of gene expression data through the analysis of transcription factor binding sites shared by sets of co-expressed genes. The system is based on cross-species sequence comparisons for phylogenetic footprinting and motif models for binding site prediction. We introduce a new set of analysis algorithms for the ...
Reliable identification of targets of bacterial regulators is necessary to understand bacterial gene expression regulation. These targets are commonly predicted by searching for high-scoring binding sites in the upstream genomic regions, which typically leads to a large number of false positives. In contrast to the common approach, here we propose a novel concept, where overrepresentation of the scoring distribution that corresponds to the entire searched region is assessed, as opposed to predicting individual binding sites. We explore two implementations of this concept, based on Kolmogorov-Smirnov (KS) and Anderson-Darling (AD) tests, which both provide straightforward P value estimates for predicted targets. This approach is implemented for pleiotropic bacterial regulators, including σ70 (bacterial housekeeping σ factor) target predictions, which is a classical bioinformatics problem characterized by low specificity. We show that KS based approach is both faster and more accurate, departing from
Systems Biology/Bioinformatics research group, Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoell Institute Search and prediction of transcription factor binding sites: challenges and solutions. Prediction of transcription factor binding sites (TFBSs) is an important step in promoter modeling and network inference. However, quality of the predictions is spoiled by numerous false positives, which persist as the main problem for all presently available TFBS search methods. We suggested a novel method (SiTaR), which allows significant reduction the number of false positives. The quality of predictions can be further improved by consideration of TFBS combinations (binding sites of cooperating TFs), which can be accomplished with the tool DistanceScan. In my talk I will give a short overview and comparison of the existing methods for TFBS search.. ...
Introduction: Competitive binding assays can be used to decipher not only the binding kinetics of studied ligands but also the binding site preference. Such assays are an essential step in the characterization of radioligands. However, the currently used competition assays require high concentrations of usually expensive ligands and still provide only binding site preference. By employing the time-resolved competition assay presented in this paper, binding characteristics including binding site preference can be obtained using less ligand. Methods: To demonstrate the appropriateness of the time-resolved competition assay, we developed an assay in which the ligand binding was interrupted with a competitor. Experiments were performed on human carcinoma cell lines expressing epidermal growth factor receptor (EGFR). The targeting of the receptor was performed with radio-iodinated epidermal growth factor (EGF). The employed competitors involved either natural ligand transforming growth factor alpha ...
In biochemistry, a binding site is a region on a protein or piece of DNA or RNA to which wigands (specific mowecuwes and/or ions) may form a chemicaw bond. An eqwiwibrium exists between unbound wigands and bound wigands.. Saturation is de fraction of totaw binding sites dat are occupied at any given time. When more dan one type of wigand can bind to a binding site, competition ensues.. Binding sites awso exhibit chemicaw specificity, a measure of de types of wigands dat wiww bond, and affinity, which is a measure of de strengf of de chemicaw bond.. Binding sites are often an important component of de functionaw characterization of biomowecuwes. For exampwe, de characterization of de active site of a substrate to an enzyme is essentiaw to modew de reaction mechanism responsibwe for de chemicaw change from substrate to product.. Binding sites on proteins can sometimes recognize oder proteins. When a binding site of one protein identifies wif anoder proteins surface, a non-covawent bond is formed ...
Background: We present Delila-genome, a software system for identification, visualization and analysis of protein binding sites in complete genome sequences. Binding sites are predicted by scanning genomic sequences with information theory-based (or user-defined) weight matrices. Matrices are refined by adding experimentally-defined binding sites to published binding sites. Delila-Genome was used to examine the accuracy of individual information contents of binding sites detected with refined matrices as a measure of the strengths of the corresponding protein-nucleic acid interactions. The software can then be used to predict novel sites by rescanning the genome with the refined matrices. Results: Parameters for genome scans are entered using a Java-based GUI interface and backend scripts in Perl. Multi-processor CPU load-sharing minimized the average response time for scans of different chromosomes. Scans of human genome assemblies required 4-6 hours for transcription factor binding sites and 10-19
Deciphering complex genetic regulatory networks encoded in a genome is a challenging problem in the post-genomic era [1]. Identifying cis-regulatory binding sites recognized by transcription factors (TF) in a genome is the first step towards this goal [2]. Since any segment of genomic sequence can be potentially a cis-regulatory binding site, a binding site motif (In this paper, we call a set of similar cis-regulatory binding sites recognized by the same TF a motif) can only be predicted by comparing multiple sequences that potentially contain the cis-regulatory binding sites sought after, based on the assumption that cis-regulatory binding sites are usually more conserved than their flanking non-functional sequences [3]. Therefore, the motif-finding problem is usually formulated to identify overrepresented segments of sequences from a set of input intergenic sequences that can be obtained by using a group of co-regulated genes in the same genome [4], or obtained by using a group of orthologous ...
The size of the second binding site equals the total amount of 125I-apoA-I bound to the cell (100 ng/mg cell protein) minus the amount of protein bound specifically to ABCA1 (3 ng/mg of cell protein). However, from the biotinylation (Figure 2) and apoA-I displacement (Figure 3) experiments, it is apparent that only around 35% of the ABCA1 is present on the surface of the cells. Hence, the actual amount of apoA-I associated with the second binding site on the surface is equal to about 30 ng of apoA-I/mg cell protein [(100 ng · 0.35)−3 ng)]. It follows that the amount of apoA-I associated with the second site is some 10-fold greater than that bound to ABCA1 indicating that the second site is a high capacity binding site (Figure 6), as has been postulated previously.4. Cross-linking of bound apoA-I followed by immunoprecipitation with anti-apoA-I has demonstrated that, apart from ABCA1, apoA-I does not bind to any other cellular protein (Figure 4B). In fact, ≈90% of the bound apoA-I is ...
Transcription factors are DNA-binding proteins that control gene transcription by binding specific short DNA sequences. Experiments that identify transcrip- tion factor binding sites are often laborious and expensive, and the binding sites of many transcription factors remain unknown. We present a computa- tional scheme to predict the binding sites directly from transcription factor se- quence using all-atom molecular simulations. This method is a computational counterpart to recent high-throughput experimental technologies that identify transcription factor binding sites (ChIP-chip and protein-dsDNA binding mi- croarrays). The only requirement of our method is an accurate 3D structural model of a transcription factor DNA complex. We apply free energy calcula- tions by thermodynamic integration to compute the change in binding energy of the complex due to a single base pair mutation. By calculating the binding free energy differences for all possible single mutations, we construct a position ...
To locate the ligand binding site on TLR3, we analyzed ,50 mutations within the TLR3-ECD. Remarkably, only 2 of the 50 residues tested resulted in abrogation of both the activation of TLR3 by pI:pC and the direct binding of pI:pC to purified TLR3-ECD protein. These two residues, H539 and N541, are conserved from zebrafish to humans (Fig. 10, which is published as supporting information on the PNAS web site) and position the ligand binding site on the glycan-free surface of the ECD at LRR20.. Replacing His-539 with an alanine has little effect on TLR3 responsiveness, whereas substitution of a negatively charged carboxyl group for an imidazole ring at this site results in a total loss of function. This finding suggests that a negative charge from a backbone phosphate group on dsRNA occupies a position in close proximity to residue 539 in the ligand-receptor complex. In the WT protein a protonated imidazole ring of His-539 would neutralize the negative charge of the phosphate, but in the H539E ...
The crystal structures of jacalin complexed with Gal alpha-(1,4) Gal and Gal alpha-(1,3) Gal beta-(1,4) Gal have been determined with the primary objective of exploring the effect of linkage on the location of reducing and non-reducing sugars in the extended binding site of the lectin, an issue which has not been studied thoroughly. Contrary to the earlier surmise based on simple steric considerations, the two structures demonstrate that alpha-linked sugars can bind to jacalin with nonreducing sugar at the primary binding site. This is made possible substantially on account of the hitherto underestimated plasticity of a non-polar region of the extended binding site. Modeling studies involving conformational search and energy minimization, along with available crystallographic and thermodynamic data, indicate a strong preference for complexation with Gal beta-(1,3) Gal with the reducing Gal at the primary site, followed by that with Gal alpha-(1,3) Gal, with the reducing or non-reducing Gal ...
Here we report experiments analysing the DNA‐binding activity of endo VII with respect to participating regions of the protein and their mode of interaction. The results show: (i) both ends of the endo VII polypeptide chain are involved in DNA binding; (ii) N‐ and C‐termini from different subunits are in close proximity in the active protein; (iii) one N‐ and one C‐terminus, each originating from a different subunit, form one DNA‐binding site; and (iv) the endo VII dimer has two DNA‐binding sites, either one of which is sufficient for specific binding to cruciform DNA.. It was found recently that the C‐terminus of endo VII is essential for DNA binding, and removal of more than three amino acids from the C‐terminus abolished the binding to cruciform DNA completely (Golz et al., 1997). This was confirmed in this study by using peptides lacking 10 or 37 C‐terminal amino acids which were also completely inactive in DNA binding. Here we describe that the N‐terminus is also ...
The interactions of the lead inhibitors, ASN03779174, Selleckchem MG132 ASN09646888 and ASN04208384, for RTP, SAH and SAM sites of MTase respectively, are shown in Table 3. Novel ligand interactions with active site of MTase are shown in Fig. 3. The dengue virus MTase has two binding sites; RNA binding site and SAM binding site, which can be targeted to find the lead molecules from the known ligands using e-pharmacophore. Glide ligand docking was performed using the known ligands of RTP, SAH and SAM with their respective binding sites of methyltransferase. These protein-ligand. complexes were further used to find the energy based pharmacophore. The pharmacophore features for the three ligands include ADDDN, ADNR and AADDNNR respectively. Three different pharmacophore hypothesis for the above three ligands (RTP, SAH and SAM) were taken to screen the Asinex database to find the novel molecules for the two different binding PF-01367338 mouse sites. Pharmacophore screening resulted in 38 molecules ...
The binding modes of a DNA or RNA binding protein refer to the different possible stable binding conformations between the protein and the nucleic acids. There are two main factors that can produce multiple modes of binding:. 1. Many proteins can contain multiple DNA and RNA binding domains with different sequence-binding preferences. When different combinations of these domains bind to different binding sites, we refer to each DNA or RNA interacting combination as a binding mode of the protein.. 2a. Many proteins can oligomerize into homo- and heterodimers and tetramers - whereby the protein-complex now has more DNA and/or RNA binding domains to bind to larger binding sites. In addition, many of these oligomerizing proteins can also bind as monomers to smaller sites. Often, differently sized protein-complexes have different binding properties and are referred to as having different binding modes. "Latent specificity" is when the binding specificity of a protein changes significantly when bound ...
Locations of anti-AIDS drug binding sites and resistance mutations in the three-dimensional structure of HIV-1 reverse transcriptase. Implications for mechanisms of drug inhibition and resistance.
In article ,9501041949.AA28566 at silibone.cchem.berkeley.edu,, yang at SILIBONE.CCHEM.BERKELEY.EDU wrote: , , We are looking for programs which search backbone structures for metal-binding , sites--specifically, we are interested in designing such sites in , non-metallo enzymes in order to improve catalysis. Thanks in advance! Youre probably aware of WHATIF by G.Vriend - if not, check Vriend, J.Mol.Graph, 8:52-56, and Proteins Struct.Funct. Genet. 11:52-58. To obtain a licence, contact ,vriend at embl-heidelberg.de,. This should help with identifying binding sites. The question of how to put ligand binding sites into your protein is a different matter. You need to identify those residues of your target structure, which are closest in 3D structure to the binding site. But you know in advance neither where these residues are going to be, nor even in what order they should be in the target sequence. For example, a three His zinc binding site may be -1-..-2-..-3- in the binding site from the ...
There are many different groups that are developing software for finding transciption factor binding sites, alongside our own development of the BIFA tool which forms part of the Apples framework. ...
We next asked why the mutations we had identified in primary patient T-ALLs were clustered in a defined genomic location. A search for predicted transcription factor binding sites near the MuTE site identified the preferred binding sequences for RUNX1, GATA3, and ETS1, as well as E-box motifs characteristic of binding by TAL1/E-protein heterodimers (fig. S5). The absence of predicted MYB binding sites in the wild-type sequence suggests that the MuTE is critical for MYB binding and supports our hypothesis that MYB binding to its de novo motif is crucial to binding by members of the TAL1 complex at this hotspot. To explore this concept further, we extracted the raw ChIP-seq reads and determined the allelic frequency of mutant to wild-type reads of bound DNA fragments at the mutation site. Note that, in MOLT-3 cells, both MYB and TAL1 bound predominantly to the mutant allele, with 67 of the 68 reads, and 37 of 38 reads, revealing the mutant sequence in the bound DNA. Likewise, in Jurkat cells, 404 ...
The ongoing debate over junk DNA often revolves around data collected by ENCODE and others. The idea that most of our genome is transcribed (pervasive transcription) seems to indicate that genes occupy most of the genome. The opposing view is that most of these transcripts are accidental products of spurious transcription. We see the same opposing views when it comes to transcription factor binding sites. ENCODE and their supporters have mapped millions of binding sites throughout the genome and they believe this represent abundant and exquisite regulation. The opposing view is that most of these binding sites are spurious and non-functional.. The messy view is supported by many studies on the biophysical properties of transcription factor binding. These studies show that any DNA binding protein has a low affinity for random sequence DNA. They will also bind with much higher affinity to sequences that resemble, but do not precisely match, the specific binding site [How RNA Polymerase Binds to ...
The ongoing debate over junk DNA often revolves around data collected by ENCODE and others. The idea that most of our genome is transcribed (pervasive transcription) seems to indicate that genes occupy most of the genome. The opposing view is that most of these transcripts are accidental products of spurious transcription. We see the same opposing views when it comes to transcription factor binding sites. ENCODE and their supporters have mapped millions of binding sites throughout the genome and they believe this represent abundant and exquisite regulation. The opposing view is that most of these binding sites are spurious and non-functional.. The messy view is supported by many studies on the biophysical properties of transcription factor binding. These studies show that any DNA binding protein has a low affinity for random sequence DNA. They will also bind with much higher affinity to sequences that resemble, but do not precisely match, the specific binding site [How RNA Polymerase Binds to ...
The ongoing debate over junk DNA often revolves around data collected by ENCODE and others. The idea that most of our genome is transcribed (pervasive transcription) seems to indicate that genes occupy most of the genome. The opposing view is that most of these transcripts are accidental products of spurious transcription. We see the same opposing views when it comes to transcription factor binding sites. ENCODE and their supporters have mapped millions of binding sites throughout the genome and they believe this represent abundant and exquisite regulation. The opposing view is that most of these binding sites are spurious and non-functional.. The messy view is supported by many studies on the biophysical properties of transcription factor binding. These studies show that any DNA binding protein has a low affinity for random sequence DNA. They will also bind with much higher affinity to sequences that resemble, but do not precisely match, the specific binding site [How RNA Polymerase Binds to ...
The ongoing debate over junk DNA often revolves around data collected by ENCODE and others. The idea that most of our genome is transcribed (pervasive transcription) seems to indicate that genes occupy most of the genome. The opposing view is that most of these transcripts are accidental products of spurious transcription. We see the same opposing views when it comes to transcription factor binding sites. ENCODE and their supporters have mapped millions of binding sites throughout the genome and they believe this represent abundant and exquisite regulation. The opposing view is that most of these binding sites are spurious and non-functional.. The messy view is supported by many studies on the biophysical properties of transcription factor binding. These studies show that any DNA binding protein has a low affinity for random sequence DNA. They will also bind with much higher affinity to sequences that resemble, but do not precisely match, the specific binding site [How RNA Polymerase Binds to ...
Influenza A virus M2 (A/M2) forms a homotetrameric channel in viral membranes that is highly selective for protons. A/M2 has been extensively studied by electrophysiologists, biophysicists, structural biologists and biochemists in order to understand the mechanism and selectivity of proton conductance from the structural basis. Medicinal chemists have also studied A/M2 as therapeutic target for anti-flu drugs. However, research on A/M2 drug binding lead to entirely different binding sites of two very similar anti-flu drugs. In light of the urgency in developing novel antivirals against drug resistant A/M2 mutants, it is imperative to solve this discrepancy in order to guide the next generation of antiviral discovery. This highly contentious debate was settled in favor of pore blocking through collaborate efforts with Dr. Mei Hong in Iowa State University. We showed by solid state NMR that the single high affinity pharmacologically relevant drug binding site locates at the N-terminal lumen with amine
We study a set of transcription factors (TFs) including the hypoxia-inducible factor 1 (HIF-1) involved in regulation of hypoxia response in human cells. We demonstrate that binding sites for a pair of interacting TFs can be found at distances that are dr
DBSI :: DESCRIPTION DBSI (DNA Binding Site Identifier), is a binding site predictor for DNA, and it has also successfully identified binding sites for RNA and heparin. ::DEVELOPER Mitchell Lab :: SCREENSHOTS
Conservation of information between prokaryotic and eukaryotic regulatory proteins and their cognate binding sites on DNA and RNA (operators and response elements) has been observed and is proposed as a basis for site-specific recognition. We present anal
IL-17C is an associate of the IL-17 family of cytokines. to bind to all three recognized binding sites. Moreover NF-κB binding to these sites was inducible by TNFα. Supershift evaluation revealed binding from the NF-κB subunits p50 and p65 to all or any 3 NF-κB binding sites. To look for the contribution of NF-κB in IL-17C appearance we executed luciferase gene reporter tests and demonstrated a 3204-bp promoter fragment of IL-17C filled with three putative NF-κB binding sites was highly turned on by TNFα. Oddly enough mutations from the three NF-κB binding sites uncovered that one particular NF-κB binding site was essential for the TNFα-mediated IL-17C induction because mutation of the specific site totally abolished TNFα-induced KU-60019 IL-17C promoter activation. We conclude which the activation of NF-κB (p65/p50) is essential for the TNFα-induced arousal of IL-17C appearance in individual keratinocytes. (1). It is one of the IL-17 category of cytokines which includes six ...
C1D was isolated as a protein with exceptional DNA affinity, since it remained bound to DNA under denaturing conditions (alkaline extraction and phenol extraction) [1], and Rrp47 and C1D both bind to circular plasmids or linear double-stranded DNA in vitro [1,2]. The dissociation constant of yeast Rrp47 for DNA is comparable with that for RNA, both being approx. 1 μM (calculating the protein concentration based on the predicted molecular mass of the monomeric protein) [2]. RNA is an effective competitor in a DNA-binding assay [2], strongly suggesting that the ligands occupy the same binding site on Rrp47. The expression level of Rrp47 is comparable with that of Rrp6 [2], which is reported to be approx. 2000 molecules per yeast cell [36]. Given the volume of a yeast cell nucleus is approx. 3 μm3 [37], the intracellular concentration of Rrp47 is close to its dissociation constant. Changes in the effective concentration of Rrp47 would therefore have a large impact on its ability to bind ...
A new method for identifying sites of protein-DNA interaction genome-wide, |I cmid=Science Spotlight Article:Abstract|in vivo|/i| reveals binding kinetics. 
An example of greater avidity is the IgM pentamer. Individually, each bond is easily broken but when many are present at the same time the overall effect results in synergistic, strong binding of antigen to antibody: IgM has low affinity but high avidity because it has 10 weak binding sites as opposed to the 2 strong binding sites of IgG or IgE ...
This article is of two parts: (a) the development of a protein reduced representation and its implementation in a Web server; and (b) the use of the reduced protein representation in the modeling of the binding site of a given ligand and the screening for the model in other protein 3D structures. Current methods of reduced protein 3D structure representation such as the Cα trace method not only lack essential molecular detail, but also ignore the chemical properties of the component amino acid side chains. This chapter describes a reduced protein 3D structure representation called
Visualization of Protein 3D Structures in Double-Centroid Reduced Representation: Application to Ligand Binding Site Modeling and Screening: 10.4018/978-1-4666-3604-0.ch059: This article is of two parts: (a) the development of a protein reduced representation and its implementation in a Web server; and (b) the use of the reduced
It has not eluded note that calcium ion is also a significant parameter; after all, it has been documented for more than half a century [4] that secretion rate is proportional to [Ca]M, where [Ca] is Ca2+ concentration and M is the number of cooperating ions (0 ≤ M ≤ 5), reflecting that multiple Ca2+ ions binding to M-sites are required for fusion acceleration [2]. Such relation, well documented for exocytosis and recently confirmed also for homotypic fusion [25], is not surprising; Ca2+ ions are the key ions required for the finalization of membrane fusion. In the case of Ca2+ ion binding, the first Ca2+ ion has three to five different locations (depending on the ligand protein) where it can bind [2,8-13]. In case M , 1, the reaction is positively cooperative, namely the first Ca2+ ion binding to a site increases the protein-Ca2+ ion complex affinity at other binding sites. This represents a state of higher entropy compared with binding the last Ca2+ ion, which has only one location where ...
Sequence-specific transcription factor which is part of a developmental regulatory system that provides cells with specific positional identities on the anterior-posterior axis. Binds to sites in the 5-flanking sequence of its coding region with various affinities. The consensus sequences of the high and low affinity binding sites are 5-TAATGA[CG]-3 and 5-CTAATTTT-3.
Is there a free software program that will allow you to enter your sequence of interest and search for a consensus binding sequence that you also specify? I know there are resources on the net but I dont know which one would allow me to enter both the DNA sequence and the transcription factor binding sequence as well. Any advice would be greatly appreciated. Thanks much ...
Ralf Eggeling, Teemu Roos, Petri Myllymäki, and Ivo Grosse authored a paper Inferring intra-motif dependencies of DNA binding sites from ChIP-seq data that was accepted for publication in BMC Bioinformatics.. Eggeling recently defended his PhD thesis at the Halle-Wittenberg University in Germany, supervised by Grosse. Ralf then joined HIIT as a postdoctoral researcher.. ...
On the basis of mutagenesis studies, four different molecular models for the agonist binding site were proposed, none of which was consistent with the binding site constructed from the published crystal structure of the zfP2X4 receptor (Kawate et al., 2009; Browne et al., 2010; Young, 2010). First, it was suggested that the ATP action is coordinated by positively charged lysine residues interacting with the negatively charged phosphate tail of ATP and the adenine ring is coordinated by the aromatic phenylalanine residues Phe185 and Phe291 in P2X1 (Phe171 and Phe280 with P2X3 numbering) (Roberts et al., 2006; Evans, 2010). However, Phe174 is located outside the binding pouch and ∼10 Å away from our favored binding configuration. Phe280 is located between Asn279 and Arg281 but at the opposing side of the β-strand, which is buried in the crystal structure. A slight conformational change of the receptor after ATP binding may move the adenine ring nearer to Phe280, helping to establish ...
The main cavities available for ligand binding in FtsZ monomer are the nucleotide-binding cup in the N-terminal domain and the long cleft between N- and C-terminal domains, known as PC190723 binding site (Figure A). The nucleotide binding site in FtsZ is conserved among FtsZs from different organisms (Oliva et al., 2007). Some compounds targeting the nucleotide site have similar chemical structure to the nucleotide, such as the C8-GTP derivatives that selectively inhibit FtsZ but promote tubulin assembly (Lappchen et al., 2008), while others have different chemical structures such as PC170942 (Stokes et al., 2005). In this Thesis, the effects on the functional activity of FtsZ of both types of ligands have been examined. The discovery of the PC190723 binding site in FtsZ is recent(Haydon et al., 2008) andthe crystal structure of FtsZ with bound PC190723 was made available last year (Elsen et al., 2012; Tan et al., 2012 and Matsui et al., 2012). Few compounds that bind to this site have been ...
A Binding Site Plan (BSP) is a division of land for office, commercial or industrial zoned properties or a manufactured home park. A pre-application meeting with staff is required to discuss your proposal before a formal application is submitted. Additionally, lots may be established through a record of survey subsequent to the recording of the initial binding site plan. To find out more information, go to Section 20.60.040 in the Municipal Code. You will need the application listed as Establish Lots w/in a BSP Application to apply ...
2QOS: Crystal structure of complement protein C8gamma in complex with a peptide containing the C8gamma binding site on C8alpha: Implications for C8gamma ligand binding.
A Proliferation Inducing Ligand (APRIL) is a TNF ligand that, via its receptors TACI and BCMA, is involved in both B cell physiology as well as in proliferation and survival of malignant B cells. To target APRIL-dependent stimulation of B cell cancers, we recently produced and characterized two monoclonal antagonistic anti-human APRIL antibodies called humanAPRIL.01A (hA.01A) and humanAPRIL.03A (hA.03A). In a first biochemical assay to validate their blocking activity, hA.01A was shown to fully prevent APRIL from binding to its receptors, whereas a substantial difference was detected for hA.03A, which inhibited APRIL binding to BCMA less efficiently than hA.01A. Epitope mapping subsequently revealed that hA.01A and hA.03A bind distinct sites on APRIL, which provided a structural rationale of their different blocking activities. Importantly, this differential inhibition profile can be used to functionally dissect BCMA and TACI-dependent signals and indicated that B cell survival and IgA ...
The long-range electrostatic forces of the targets in round 2 of the Critical Assessment of PRediction of Interactions (CAPRI) experiment were examined and a simple guided docking method, based on these forces, was applied. The method described consists of calculating an initial rigid body trajectory and an optional final, fully flexible refinement stage. Although only limited success was found in predicting the final complexes, some interesting information was discovered. In particular, the long-range forces seem to give some insight into the unusual binding mode of target 4 while raising some questions about target 7, which warrant further investigation.
COMMENTS: The sequences shared by SpAN protein binding sites III and VI are similar to consensus binding site for SpGCF1. Site III contains a 20/21 identity to the SpGCF1 consensus. It was shown that complexes formed at sites III and VI are supershifted by addition of an antibody raised against recombinant SpGCF1. Control serum does not cause a mobility shift and complexes formed at other SpAN sites are not supershifted by the anti-SpGCF1 antibody. ...
A drug which attenuates the effect of an agonist. It may be competitive (or surmountable), i.e. it binds reversibly to a region of the receptor in common with an agonist, but occupies the site without activating the effector mechanism. The effects of a c ompetitive antagonist may be overcome by increasing the concentration of agonist, thereby shifting the equilibrium and increasing the proportion of receptors which the agonist occupies. This type of antagonist is discussed further in the next section. Alternatively, antagonists may be unsurmountable, where no amount of agonist can completely overcome the inhibition once it has been established. Unsurmountable antagonists may bind covalently to the agonist binding site (competi tive irreversible antagonists), in which case there is a period before the covalent bond forms during which competing ligands can prevent the inhibition. Other types of unsurmountable antagonists act allosterically at a different site on the receptor or an associated ion ...
In LDL-receptors the class A domains form the binding site for LDL [1] and calcium [5]. The acidic residues between the fourth and sixth cysteines are important for high-affinity binding of positively charged sequences in LDLRs ligands [6]. The repeat has been shown [2] to consist of a β-hairpin structure followed by a series of β turns. The binding of calcium seems to induce no significant conformational change. Last update: April 2006 / Pattern revised. ...
The chief attribute of proteins that also permits their diverse list of features is their capability to bind other molecules specifically and tightly. The area from the protein chargeable for binding One more molecule is known as the binding web-site and is commonly a depression or pocket over the molecular surface. This binding skill is mediated from the tertiary structure with the protein, which defines the binding site pocket, and with the chemical Houses of the bordering amino acids side chains ...
In contrast, the mAb PC61, that was previously reported to recognize a determinant distal to the IL-2 binding site on the mouse p55 subunit of IL-2R and to dissociate IL-2 from the high-affinity IL-2R complex by altering the conformation of the p55 molecule itself, inhibited the low-affinity binding and cross-linking of IL-2 to the p55 molecule on mouse p55 cDNA-transfected cells ...
1J2T: Crystal structures of creatininase reveal the substrate binding site and provide an insight into the catalytic mechanism
Dear Cpanel Users and Gurus Actually in IIS there is Site Bindings which can let you add another Site http...
The drugs Prevacid and Prilosec have a different active ingredient, a different propensity for causing allergic reactions, and may differ in their ability to treat certain conditions, according to...
When we talk about historical sites we may be inclined to think about ancient ones. It is true that ancient historical sites might tell their stories about the activities and ways of living of our
Divergence of transcription factor binding sites is considered to be an important source of regulatory evolution. The associations between transcription factor binding sites and phenotypic diversity have been investigated in many model organisms. However, the understanding of other factors that contribute to it is still limited. Recent studies have elucidated the effect of chromatin structure on molecular evolution of genomic DNA. Though the profound impact of nucleosome positions on gene regulation has been reported, their influence on transcriptional evolution is still less explored. With the availability of genome-wide nucleosome map in yeast species, it is thus desirable to investigate their impact on transcription factor binding site evolution. Here, we present a comprehensive analysis of the role of nucleosome positioning in the evolution of transcription factor binding sites. We compared the transcription factor binding site frequency in nucleosome occupied regions and nucleosome depleted regions
BackgroundIn studies of gene regulation the efficient computational detection of over-represented transcription factor binding sites is an increasingly important aspect. Several published methods can be used for testing whether a set of hypothesised co-regulated genes share a common regulatory regime based on the occurrence of the modelled transcription factor binding sites. However there is little or no information available for guiding the end users choice of method. Furthermore it would be necessary to obtain several different software programs from various sources to make a well-founded choice.MethodologyWe introduce a software package, Asap, for fast searching with position weight matrices that include several standard methods for assessing over-representation. We have compared the ability of these methods to detect over-represented transcription factor binding sites in artificial promoter sequences. Controlling all aspects of our input data we are able to identify the optimal statistics across
This unit describes how to use the Transcription Element Search System (TESS). This Web site predicts transcription factor binding sites (TFBS) in DNA sequence using two different kinds of models of sites, strings and positional weight matrices. The binding of transcription factors to DNA is a major part of the control of gene expression. Transcription factors exhibit sequence-specific binding; they form stronger bonds to some DNA sequences than to others. Identification of a good binding site in the promoter for a gene suggests the possibility that the corresponding factor may play a role in the regulation of that gene. However, the sequences transcription factors recognize are typically short and allow for some amount of mismatch. Because of this, binding sites for a factor can typically be found at random every few hundred to a thousand base pairs. TESS has features to help sort through and evaluate the significance of predicted sites. Curr. Protoc. Bioinform. 21:2.6.1-2.6.15. © 2008 by John ...
Understanding transcription is central to understanding genetic regulatory mechanisms. The transcription of a gene is generally dependent on the presence of specific signals located at upstream regions of the core-promoter. These specific signals derive from their use as binding sites by transcription factors (TFs), and are therefore termed transcription factor binding sites (TFBSs). Recently, chromatin immunoprecipitation followed by cDNA microarray hybridization (ChIP-chip array) has been used to identify potential regulatory sequences, but the procedure can only map the probable protein-DNA interaction loci within 1-2 kilobases resolution [1]. To find out the exact binding motifs, it is necessary to build a computational method to examine the ChIP-chip array binding sequences and search for possible motifs representing the TFBSs (motif discovery).. There are many computational TFBS motif finding tools available [2-4]. The traditional approach for finding TFBSs is to collect and align a set of ...
ABSTRACT: One goal of human genetics is to understand how the information for precise and dynamic gene expression programs is encoded in the genome. The interactions of transcription factors (TFs) with DNA regulatory elements clearly play an important role in determining gene expression outputs, yet the regulatory logic underlying functional transcription factor binding is poorly understood. Many studies have focused on characterizing the genomic locations of TF binding, yet it is unclear to what extent TF binding at any specific locus has functional consequences with respect to gene expression output. To evaluate the context of functional TF binding we knocked down 59 TFs and chromatin modifiers in one HapMap lymphoblastoid cell line. We then identified genes whose expression was affected by the knockdowns. We intersected the gene expression data with transcription factor binding data (based on ChIP-seq and DNase-seq) within 10 kb of the transcription start sites of expressed genes. This ...
ABSTRACT: One goal of human genetics is to understand how the information for precise and dynamic gene expression programs is encoded in the genome. The interactions of transcription factors (TFs) with DNA regulatory elements clearly play an important role in determining gene expression outputs, yet the regulatory logic underlying functional transcription factor binding is poorly understood. Many studies have focused on characterizing the genomic locations of TF binding, yet it is unclear to what extent TF binding at any specific locus has functional consequences with respect to gene expression output. To evaluate the context of functional TF binding we knocked down 59 TFs and chromatin modifiers in one HapMap lymphoblastoid cell line. We then identified genes whose expression was affected by the knockdowns. We intersected the gene expression data with transcription factor binding data (based on ChIP-seq and DNase-seq) within 10 kb of the transcription start sites of expressed genes. This ...
ABSTRACT: One goal of human genetics is to understand how the information for precise and dynamic gene expression programs is encoded in the genome. The interactions of transcription factors (TFs) with DNA regulatory elements clearly play an important role in determining gene expression outputs, yet the regulatory logic underlying functional transcription factor binding is poorly understood. Many studies have focused on characterizing the genomic locations of TF binding, yet it is unclear to what extent TF binding at any specific locus has functional consequences with respect to gene expression output. To evaluate the context of functional TF binding we knocked down 59 TFs and chromatin modifiers in one HapMap lymphoblastoid cell line. We then identified genes whose expression was affected by the knockdowns. We intersected the gene expression data with transcription factor binding data (based on ChIP-seq and DNase-seq) within 10 kb of the transcription start sites of expressed genes. This ...
ABSTRACT: One goal of human genetics is to understand how the information for precise and dynamic gene expression programs is encoded in the genome. The interactions of transcription factors (TFs) with DNA regulatory elements clearly play an important role in determining gene expression outputs, yet the regulatory logic underlying functional transcription factor binding is poorly understood. Many studies have focused on characterizing the genomic locations of TF binding, yet it is unclear to what extent TF binding at any specific locus has functional consequences with respect to gene expression output. To evaluate the context of functional TF binding we knocked down 59 TFs and chromatin modifiers in one HapMap lymphoblastoid cell line. We then identified genes whose expression was affected by the knockdowns. We intersected the gene expression data with transcription factor binding data (based on ChIP-seq and DNase-seq) within 10 kb of the transcription start sites of expressed genes. This ...
L.Y.Wang, M. Snyder, M. Gerstein In order to understand the molecular mechanisms of gene regulation, a robust method is required to discriminate transcription factor binding sites from non-binding sites on a genomic scale. Experimental methods such as ChIP-chip experiments (microarray-based readout of chromatin immuno-precipitation assays), though gaining great success, remain time-consuming, expensive, and noisy. Traditional computational methods for binding site identification, such as consensus sequences, profile methods, and HMMs, are known to generate high false positive rates when applied genome-wide. They are based on training only with positive data, the small numbers of known binding sites. Thus, we are motivated to propose a new computational method to discover transcription-factor binding sites that synthesizes the noisy data from ChIP-chip experiments with known positive binding-site patterns. Our method (which we call BoCaTFBS) uses a boosted cascade of classifiers, where each ...
Shigella flexneri is a gram-negative, invasive bacterial pathogen that afflicts the human colonic epithelium, causing shigellosis, an illness triggering severe dysentery. The World Health Organization cites the disease burden of shigellosis near 90 million episodes and 108,000 deaths per year. The motility and spread of Shigella is modulated by icsP, a virulence gene. The transcription factor VirB positively regulates many virulence genes encoded by the Shigella virulence plasmid. Two distal binding sites of VirB have been shown to regulate the promoter activity of icsP, despite their location of more than 1 kb upstream of the transcription start site. Five VirB binding sites are located between these two sites and the transcription start site, and two are located in close proximity downstream of the transcription start site. Investigation into the impact of the VirB binding sites is part of a larger effort to understand the workings of VirB, which is the major switch that controls virulence gene
Profacgen, a cutting-edge life science company pioneering protein services that accelerate pharmaceutical development, announces the launch of Protein Binding Site Mapping Service. Scientists in the field of protein interaction study can now have access to this novel service.. Protein-protein interactions (PPIs) play essential roles in almost all cellular processes, including gene regulation, metabolic control, signal transduction, and cell communication. Surface plasmon resonance (SPR) spectroscopy is a rapidly developing technique for the study of binding events involving proteins, which are the major molecular targets for validated drugs and for current drug discovery.. Profacgen employs SPR techniques to identify binding sites involved in protein-protein interactions. Its protein binding site mapping service is highly customizable, which suits their customers specific research goals. According to its official speaker, the customer only need to send the company the target protein sequence ...
The multidrug resistance P-glycoprotein (P-gp) is characterised by the ability to bind and/or transport an astonishing array of drugs. This poly-specificity is imparted by at least four pharmacologically distinct binding sites within the transmembrane domain. Whether or not these sites are spatially distinct has remained unclear. Biochemical and structural investigations have implicated a central cavity as the likely location for the binding sites. In the present investigation, a number of contact residues that are involved in drug binding were identified through biochemical assays using purified, reconstituted P-gp. Drugs were selected to represent each of the four pharmacologically distinct sites. Contact residues important in rhodamine123 binding were identified in the central cavity of P-gp. However, contact residues for the binding of vinblastine, paclitaxel and nicardipine were located at the lipid-protein interface rather than the central cavity. A key residue (F978) within the central ...
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GCC185, a trans-Golgi network-localized protein predicted to assume a long, coiled-coil structure, is required for Rab9-dependent recycling of mannose 6-phosphate receptors (MPRs) to the Golgi and for microtubule nucleation at the Golgi via CLASP proteins. GCC185 localizes to the Golgi by cooperative interaction with Rab6 and Arl1 GTPases at adjacent sites near its C terminus. We show here by yeast two-hybrid and direct biochemical tests that GCC185 contains at least four additional binding sites for as many as 14 different Rab GTPases across its entire length. A central coiled-coil domain contains a specific Rab9 binding site, and functional assays indicate that this domain is important for MPR recycling to the Golgi complex. N-Terminal coiled-coils are also required for GCC185 function as determined by plasmid rescue after GCC185 depletion by using small interfering RNA in cultured cells. Golgi-Rab binding sites may permit GCC185 to contribute to stacking and lateral interactions of Golgi cisternae as
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After decades of work, the correct determination of the binding mode of a small molecule into a target protein is still a challenging problem, whose difficulty depends on: (i) the sizes of the binding site and the ligand; (ii) the flexibility of both interacting partners, and (iii) the differential solvation of bound and unbound partners. We have evaluated the performance of standard rigid(receptor)/flexible(ligand) docking approaches with respect to last-generation fully flexible docking methods to obtain reasonable poses in a very challenging case: soluble Epoxide Hydrolase (sEH), a flexible protein showing different binding sites. We found that full description of the flexibility of both protein and ligand and accurate description of solvation leads to significant improvement in the ability of docking to reproduce well known binding modes, and at the same time capture the intrinsic binding promiscuity of the protein ...
SoxS is the direct transcriptional activator of the member genes of the Escherichia coli superoxide regulon. At class I SoxS-dependent promoters, e.g. zwf and fpr, whose SoxS binding sites (soxbox) lie upstream of the -35 region of the promoter, activation requires the C-terminal domain of the RNA polymerase alpha-subunit, while at class II SoxS-dependent promoters, e.g. fumC and micF, whose binding sites overlap the -35 region, activation is independent of the alpha-CTD. To determine whether SoxS activation of its class I promoters shows the same helical phase-dependent spacing requirement as class I promoters activated by catabolite gene activator protein, we increased the 7 bp distance between the 20 bp zwf soxbox and the zwf -35 promoter hexamer by 5 bp and 11 bp, and we decreased the 15 bp distance between the 20 bp fpr soxbox and the fpr -35 promoter hexamer by the same amounts. In both cases, displacement of the binding site by a half or full turn of the DNA helix prevented ...
The present invention is related to methods and compositions that are capable of immediately immunizing a human or animal against any molecule or compound. The present invention comprises an immunity linker molecule with at least two sites; (1) a first binding site that binds to an immune system molecule in a human or animal that has been preimmunized against the first binding site, and (2) one or more second binding sites that bind specifically to a desired compound or molecule. The first binding site and the second binding site(s) are linked by a linker portion of the molecule.
View Notes - Bio 15 from BIOL 101 at UPenn. 1) Histidine, Glycine, Histidine, Leucine, Tyrosine 2) Transcription starts at binding sites called promoters on the DNA template strand, as opposed to the
Nordic Capital Fund VII ("Nordic Capital") has acquired The Binding Site Corporation Limited ("Binding Site" or "the Company"), a privately-owned specialist diagnostics company, from its founder, Jo Bradwell. The parties have agreed not to disclose the sales price. Professor Bradwell will retain a small share of the Company, and remain on the Board.. Binding Site, based in Birmingham, UK, specialises in the research, development, manufacture and sale of innovative medical diagnostic products focused on Multiple Myeloma and other B-Cell dyscrasias and Primary Immunodeficiency (PID). With extensive expertise in antibody specificity technology, Binding Site gives clinicians and laboratory staff tools to improve diagnosis and management of patients across a range of B-cell cancers and immune system disorders.. Following the acquisition by Nordic Capital, Binding Site will continue to build on its position as the worlds leading supplier of IVD assays for identifying and monitoring B-Cell dyscrasias ...
A free inside look at Binding Site salary trends. 7 salaries for 6 jobs at Binding Site. Salaries posted anonymously by Binding Site employees.
BioAssay record AID 150617 submitted by ChEMBL: Concentration required for 50% inhibition (racemic) at binding site of human P-Glycoprotein (P-gp) in one-affinity model.
Group II introns are large metallo-ribozymes that use divalent metal ions in folding and catalysis. The 3-terminal domain 6 contains a conserved adenosine whose 2-OH acts as the nucleophile in the first splicing step. In the hierarchy of folding, D6 binds last into the active site. In order to investigate and understand the folding process to the catalytically active intron structure, it is important to know the individual binding affinities of Mg2+ ions to D6. We recently studied the solution structure of a 27 nucleotide long domain 6 (D6-27) from the mitochondrial yeast group II intron Sc.ai5, identifying also five Mg2+ binding sites including the one at the 5-terminal phosphate residues. Mg2+ coordination to the 5-terminal di- and triphosphate groups is strongest (e.g., log KA,TP = 4.55 ± 0.10) and could be evaluated here in detail for the first time. The other four binding sites within D6-27 are filled simultaneously (e.g., log KA,BR = 2.38 ± 0.06) and thus compete for the free Mg2+ ...
The regulation of a gene depends on the binding of transcription factors to specific sites located in the regulatory region of the gene. The generation of these binding sites and of cooperativity between them are essential building blocks in the evolution ...
Im trying to search for binding sites for the transcription factor MAF (i.e. TFBS for MAF) in the promoter regions of various genes. I initially started out
The conjugative S. ambofaciens integrative element pSAM2 possesses a kil-kor system. The korSA gene has been identified as a key element of this system, and thekil locus has been located in the region oftraSA, the main transfer gene (7, 25), but the direct role of KorSA in the regulation of the kil locus remained unknown. In this study we characterized the targets of the KorSA protein in the pSAM2 sequence.. Considering the relatively small size of the pSAM2 genome and the availability of its complete sequence, gel shift experiments were performed with the totality of the DNA fragments obtained after pSAM2 digestion with restriction endonucleases. Using this new approach, it was possible to demonstrate directly that KorSA binds only to the promoter regions of two pSAM2 genes, pra andkorSA, with no other binding sites detected. Unlike other known actinomycete mobile elements, KorSA did not bind either totraSA, the main pSAM2 transfer gene, or to thespdA, -B, -C, and -D genes involved in pSAM2 ...
We often think of DNA binding sites as dictating the particular transcription factor that will bind and in that way determining how transcription is regulated. However, evidence is accumulating that the interaction provides additional information and may actually allosterically modify the bound transcription factor. Leung et al. noted unusual conservation of binding sites for the transcription factor NF-κB in human and mouse genes and therefore tested the effects of single nucleotide changes on gene regulation at such a site. In mouse 3T3 cells infected with lentivirus that permitted modification of the endogenous gene promoter, a single nucleotide change was found to have no effect on binding of the transcription factor, but rather to alter the requirement for a particular coactivator, IRF3. The authors suggest that conformational changes in the bound NF-κB molecule likely account for altered preference for cofactors when bound to different promoters. T. H. Leung, A. Hoffmann, D. Baltimore, ...
T-PIC :: DESCRIPTION T-PIC (Tree shape Peak Identification for ChIP-Seq) is a free software for determining DNA/protein binding sites from a ChIP-Seq experiment. ::DEVELOPER Valerie Hower :: SCREENSHOTS N
Chen and Jeong have essentially found a method to apply a machine learning technique called random forests to predict specific binding sites on proteins given only the amino acid sequence with greater accuracy than previously existing methods. Identification of binding sites in proteins remains an important task for both basic and applied life sciences research, for these sites make possible the protein-protein and protein-ligand interactions from which phenotypes, and indeed, the properties of life emerge. These sites also serve as important drug targets for pharmaceutical research.. Traditionally, researchers have identified binding sites from in vivo or in vitro studies involving point mutations that affect phenotypes, as well as through analysis of protein structures as identified through protein crystallography. With the advent and continuous improvement of DNA sequencing technology, however, researchers contribute ever more knowledge in the form of amino acid sequence, rather than ...
ATP-sensitive potassium (K(ATP)) channels couple cell metabolism to electrical activity by regulating K(+) fluxes across the plasma membrane. Channel closure is facilitated by ATP, which binds to the pore-forming subunit (Kir6.2). Conversely, channel opening is potentiated by phosphoinositol bisphosphate (PIP(2)), which binds to Kir6.2 and reduces channel inhibition by ATP. Here, we use homology modelling and ligand docking to identify the PIP(2)-binding site on Kir6.2. The model is consistent with a large amount of functional data and was further tested by mutagenesis. The fatty acyl tails of PIP(2) lie within the membrane and the head group extends downwards to interact with residues in the N terminus (K39, N41, R54), transmembrane domains (K67) and C terminus (R176, R177, E179, R301) of Kir6.2. Our model suggests how PIP(2) increases channel opening and decreases ATP binding and channel inhibition. It is likely to be applicable to the PIP(2)-binding site of other Kir channels, as the residues
Systems and methods for controlling patient catheters are disclosed. A system in accordance with a particular embodiment includes a catheter carrying multiple active elements, and a controller connected to the catheter. The controller can include a housing having directional indicators, and multiple control elements coupled to the multiple active elements. Individual control elements can be moveable relative to the housing to control the motion of the active elements, and the multiple control elements can be positioned so that manipulation of the multiple control elements in a first order that is clockwise or counterclockwise as identified by the directional indicators moves the multiple active elements in a first manner, and manipulation of the multiple control elements in a second order opposite the first order moves the multiple active elements in a second manner opposite the first manner.
Membrane-bound α-bungarotoxin-binding entities derived from rat brain are found to interact specifically with the affinity reagents maleimidobenzyltrimethylammonium (MBTA) and bromoacetylcholine (BAC), originally designed to label nicotinic acetylcholine receptors from electroplax and skeletal muscle. Following treatment of membranes with dithiothreitol, all specffic toxin binding sites are irreversibly blocked by reaction with MBTA or BAC. Affinity reagent labeling of dithiothreitol-reduced membranes is prevented (toxin binding sites are not blocked) by prior alkylation with N-ethylmaleimide, by prior oxidation with dithiobis(2-nitrobenzoic acid), or by incubation with neurotoxin. Reversibly associating cholinergic agonists and antagonists retard the rate of affinity reagent interaction with toxin receptors. The apparent rates of affinity reagent alkylation of toxin receptors, and the influences of other sulfhydryl/disulfide reagents on affinity labeling are comparable to those observed for ...
Involved in genome replication. Plays a crucial role, together with NSP2, in the formation of virus factories (viroplasms) which are large inclusions in the cytoplasm where core-like replication intermediates are assembled and RNA replication takes place. May regulate NSP2-RNA interactions during genome replication, since NSP5 competes with RNA for the same binding site on the NSP2 octamer. Binds to either ssRNA or dsRNA with similar affinities. Displays ATPase and autokinase activities (By similarity).
Motivation: Traditional and high-throughput techniques for determining transcription factor (TF) binding specificities are generating large volumes of data of uneven quality, which are scattered across individual databases. Results: FootprintDB integrates some of the most comprehensive freely available libraries of curated DNA binding sites and systematically annotates the binding interfaces of the corresponding TFs. The first release contains 2422 unique TF sequences, 10 112 DNA binding sites and 3662 DNA motifs. A survey of the included data sources, organisms and TF families was performed together with proprietary database TRANSFAC, finding that footprintDB has a similar coverage of multicellular organisms, while also containing bacterial regulatory data. A search engine has been designed that drives the prediction of DNA motifs for input TFs, or conversely of TF sequences that might recognize input regulatory sequences, by comparison with database entries. Such predictions can also be ...
BioAssay record AID 225886 submitted by ChEMBL: The compound was tested for its affinity for the glutamic acid binding site of the non-NMDA receptor by using [3H]-kainic acid as radioligand.
Misha and Manu have joint force (developmental biology + live imaging + quantitative image analysis) to tackle the question "is there a boundary to transcriptional enhancers?" Enhancers were identified as the minimal piece of sequence that can reproduce the endorgenous expression pattern and for historical reasons, their physical boundaries were "defined" by the restriction enzyme cutting site or pcr primer locations, both of which used by researchers to test difference pieces. Later people have found additional transcription factor binding sites outside these "minimal elements". They are not essential for "producing the expression pattern" in a reporter assay, which is qualitative and doesnt examine the fitness results. Do those additional binding sites matter? How? Check out here: PLoS Genetics ...
Human serum albumin (HSA) is an abundant plasma protein that binds a remarkably wide range of drugs, thereby restricting their free, active concentrations. The problem of overcoming the binding affinity of lead compounds for HSA represents a major challenge in drug development. Crystallographic analysis of 17 different complexes of HSA with a wide variety of drugs and small-molecule toxins reveals the precise architecture of the two primary drug-binding sites on the protein, identifying residues that are key determinants of binding specificity and illuminating the capacity of both pockets for flexible accommodation. Numerous secondary binding sites for drugs distributed across the protein have also been identified. The binding of fatty acids, the primary physiological ligand for the protein, is shown to alter the polarity and increase the volume of drug site 1. These results clarify the interpretation of accumulated drug binding data and provide a valuable template for design efforts to modulate ...
The X-ray structure of barley chitinase has been solved in our lab (Hart et al., 1993) and refined to 1.8 Å resolution (Hart et al., 1995). The structure shows a globular protein with high alpha-helical content and an elongated cleft running the length of the protein, presumably for substrate binding and catalysis. Hypothetical substrate binding models with the structure suggest that there are at least six sugar binding sites labeled A through F from the non-reducing end (Hart et al., 1995). Residues Glu 67 and Glu 89 are thought to be involved in hydrolytic catalysis, cleaving the substrate between sites D and E (Robertus et al., 1995). The putative mechanism involves protonation of the glycosidic bond at the C4 oxygen of the leaving E sugar, by Glu 67. At the same time, Glu 89 may act as a base to activate a water molecule which attacks the C1 position of the D sugar on the a side. This mechanism, suggesting that the barley chitinase catalysis proceeds with inversion of product, has been ...
This paper describes methods, results and conclusions about our study regarding the development and the optimization of a homology model of Ebola virus RNAdependent RNA p..
I have chip-seq data on histone modifications. Ive been scouring literature and blogs on Chip-seq analysis involving normalizing to input and normalizing across samples using spiked-in samples. There doesnt seem to be a cohesive differential binding analysis approach that can incorporate input normalization along with spike-in normalization. It seems most of the diff. binding approaches involves using RNA-seq methods (EdgeR, DESeq2) on read counts over genomic windows. I can substitute normalization factors used in these RNA-seq packages with spike-in normalization factors, but how do I account for input? Is blacklisting sites that are not different from input really the best way? Transforming the counts over input via log2fc or subtraction is not statistically sound (other bioinformaticians seems to agree).. Ive looked at the input signal for my data and have found signal patterns in areas consistent with some of my histone markers. This makes me think that I should really normalize my IP to ...
High-throughput protein-RNA interaction data generated by CLIP-seq has provided an unprecedented depth of access to the activities of RNA-binding proteins (RBPs), the key players in co- and post-transcriptional regulation of gene expression. Motif discovery forms part of the necessary follow-up data analysis for CLIP-seq, both to refine the exact locations of RBP binding sites, and to characterize them. The specific properties of RBP binding sites, and the CLIP-seq methods, provide additional information not usually present in the classic motif discovery problem: the binding site structure, and cross-linking induced events in reads.
Many inhibitors affect enzyme activity • Competitive inhibition - inhibitor competes for the active sites on enzyme with the substrate • Non-competitive inhibition - inhibitor binds to an allosteric site and alters the active site configuration of the enzyme • Feedback inhibition - enzyme activity is inhibited by the end product (A enzyme-1 B enzyme-2 C enzyme-3 D) - here enzyme-1 may be inhibited by product D • Feedback inhibition regulates ATP, amino acid, numcleotide and vitamin synthesis Mechanism of enzyme action • Substrate specifically binds to the active site on the surface of the enzyme and as a consequence enzyme-substrate complex is formed - can result in change of structure of the enzyme • Substrate is transformed into product by - Rearrangement of existing atoms - Breakdown of substrate molecules - Combining with other substrate molecules • Resultant products do not fit the active site and thus are released and the enzyme site becomes free for ...
One of the major challenges in the field of system biology is to understand the interaction between a wide range of proteins and ligands. In the past, methods have been developed for predicting binding sites in a protein for a limited number of ligands.. ...
wangk at chgc.sh.cn ,wangk at chgc.sh.cn, writes: , I need TRANSFAC (http://www.gene-regulation.com/pub/databases.html) to , predicate TFs and their TFBSs, but confused in finding out how can I obtain , the TRANSFAC dataset. I believe TRANSFAC is proprietary. An alternative might be Jaspar. ,From http://jaspar.genereg.net/ The JASPAR CORE database contains a curated, non-redundant set of profiles, derived from published collections of experimentally defined transcription factor binding sites for eukaryotes. The prime difference to similar resources (TRANSFAC, etc) consist of the open data acess, non-redundancy and quality. -k -- If I havent seen further, it is by standing in the footprints of giants ...
The service provides access to a database of factor-binding profiles depicting genetic makeups and structures typical of species. It provides biological researchers with lookup access to matrices defining genetic relationships documented through research. API methods generate profiles of transcription factor binding sites in varying formats, including Position Frequency Matrices (PFM), Position Weight Matrices (PWM), and Information Content Matrices (ICM). Methods support retrieval of all matrices or of a specific matrix specified by system ID or name. The API also supports search among matrices described in the system by topic-specific tags applied ...
The service provides access to a database of factor-binding profiles depicting genetic makeups and structures typical of species. It provides biological researchers with lookup access to matrices defining genetic relationships documented through research. API methods generate profiles of transcription factor binding sites in varying formats, including Position Frequency Matrices (PFM), Position Weight Matrices (PWM), and Information Content Matrices (ICM). Methods support retrieval of all matrices or of a specific matrix specified by system ID or name. The API also supports search among matrices described in the system by topic-specific tags applied ...
The multidrug transporter P-glycoprotein (P-gp) is central to the development of multidrug resistance in cancer. While residues essential for transport and binding have been identified, the location, composition, and specificity of potential drug binding sites are uncertain. Here molecular dynamics simulations are used to calculate the free energy profile for the binding of morphine and nicardipine to P-gp. We show that morphine and nicardipine primarily interact with key residues implicated in binding and transport from mutational studies, binding at different but overlapping sites within the transmembrane pore. Their permeation pathways were distinct but involved overlapping sets of residues. The results indicate that the binding location and permeation pathways of morphine and nicardipine are not well separated and cannot be considered as unique. This has important implications for our understanding of substrate uptake and transport by P-gp. Our results are independent of the choice of ...
TY - JOUR. T1 - Luminal and non-luminal non-competitive inhibitor binding sites on the nicotinic acetylcholine receptor (Review). AU - Arias, Hugo R.. PY - 1996/1/1. Y1 - 1996/1/1. N2 - The nicotinic acetylcholine receptor presents two very well differentiated domains for ligand binding that account for different cholinergic properties. In the hydrophilic extracellular region of the a subunit exist the binding sites for agonists such as the neurotransmitter acetylcholine, which upon binding trigger the channel opening, and for competitive antagonists such as d-tubocurarine, which compete for the former inhibiting its pharmacological action. For non-competitive inhibitors, a population of low-affinity binding sites have been found at the lipid-protein interface of the nicotinic acetylcholine receptor. In addition, at the M2 transmembrane domain, several high-affinity binding sites have been found for non-competitive inhibitors such as chlorpromazine, triphenylmethylphosphonium, the local ...
Saturable high and low affinity binding sites for [3H]saxitoxin were identified in myometrial membranes of pregnant rats, with dissociation constants of 0.53 and 27 nM, respectively. The maximal binding capacity of the low affinity binding sites was about 10 times higher than that of the high affinity binding sites. The dissociation constants obtained from association and dissociation kinetics of [3H]saxitoxin were similar to those obtained from equilibrium binding. Saxitoxin and tetrodotoxin specifically displaced [3H]saxitoxin binding at both types of sites. Isradipine (1-10 microM) and amiloride (50-100 microM) were without effect on the binding of [3H]saxitoxin. At high concentrations (10-100 microM), veratridine induced a partial inhibition of [3H]saxitoxin binding. In dispersed myometrial cells, [3H]saxitoxin binding revealed the presence of both high and low affinity binding sites, with KD values similar to those obtained in myometrial membranes. Sodium currents were studied in both ...
If you have a question about this talk, please contact Xin Wang.. Differences in the gene regulatory network are hypothesized to contribute significantly to phenotypic divergence between and within species. Non-coding sequences with bursts of lineage-specific changes are promising candidates, because clusters of nearby substitutions are a hallmark of selection potentially modify evolutionarily conserved regulatory elements. Performing a comprehensive, genome-wide analysis, we find that genomic loci with high substitution rates in the human-chimp lineage are over-represented near genes that duplicated in the human-chimp ancestor. We also developed a method to screen for nucleotide substitutions predicted to affect transcription factor binding. Rates of binding site divergence are elevated in non-coding sequences near duplicated loci with accelerated substitution rates. Finally, GC-biased gene conversion (gBGC) is a non-adaptive, recombination-associated explanation for accelerated substitution ...
All-trans retinoic acid (ATRA) triggers a wide range of effects on vertebrate development by regulating cell proliferation, differentiation, and apoptosis. ATRA activates retinoic acid receptors (RARs) which heterodimerize with retinoid X receptors (RXRs). RAR/RXR heterodimers function as ATRA-dependent transcriptional regulators by binding to retinoic acid response elements (RAREs). To identify RAR/RXR heterodimer-binding sites in the human genome, we performed a modified yeast one-hybrid assays and identified 193 RAR/RXR heterodimer-binding fragments in the human genome. The putative target genes included genes involved in development process and cell differentiation. Gel mobility shift assays indicated that 160 putative RAREs could directly interact with the RAR/RXR heterodimer. Moreover, 19 functional regulatory single nucleotide polymorphisms (rSNPs) on the RAR/RXR-binding sequences were identified by analyzing the difference in the DNA-binding affinities. These results provide insights into the
TY - JOUR. T1 - Prediction of inhibitor binding free energies by quantum neural networks. Nucleoside analogues binding to trypanosomal nucleoside hydrolase. AU - Braunheim, Benjamin B.. AU - Miles, Robert W.. AU - Schramm, Vern L.. AU - Schwartz, Steven D.. PY - 1999/12/7. Y1 - 1999/12/7. N2 - A computational method has been developed to predict inhibitor binding energy for untested inhibitor molecules. A neural network is trained from the electrostatic potential surfaces of known inhibitors and their binding energies. The algorithm is then able to predict, with high accuracy, the binding energy of unknown inhibitors. IU-nucleoside hydrolase from Crithidia fasciculata and the inhibitor molecules described previously [Miles, R. W. Tyler, P. C. Evans, G. Fumeaux R. H., ParK(i)n, D. W., and Schramm, V. L. (1999) Biochemistry 38, xxxx-xxxx] are used as the test system. Discrete points on the molecular electrostatic potential surface of inhibitor molecules are input to neural networks to identify the ...
Steroid sulfatases are responsible for the hydrolysis of 3beta-hydroxy steroid sulfates, such as cholesterol and pregnenolone sulfate, and have an important role in regulating the synthesis of estrogenic steroids, from estrone sulfate and dehydroepiandrosterone sulfate, in endocrine-dependent tumors. Although little is known about the mechanism by which the sulfate group is removed from a steroid nucleus, an active site-directed sulfatase inhibitor has been developed. This inhibitor, estrone-3-O-sulfamate (EMATE), was synthesized by treating the sodium salt of estrone with sulfamoyl chloride. This compound inhibited not only estrone sulfatase but also dehydroepiandrosterone sulfatase activity in placental microsomes and in intact MCF-7 breast cancer cells. Pretreatment of MCF-7 cells or placental microsomes with EMATE, followed by extensive washing or dialysis indicated irreversible inhibition. This was confirmed by showing that EMATE inhibited estrone sulfatase activity in placental microsomes in a
GO Terms Descrition:, positive regulation of transcription from RNA polymerase II promoter, anterior/posterior axis specification, cell fate specification, RNA polymerase II distal enhancer sequence-specific DNA binding transcription factor activity, transcription, DNA-templated, compound eye development, ligand-activated sequence-specific DNA binding RNA polymerase II transcription factor activity, torso signaling pathway, terminal region determination, Bolwigs organ morphogenesis, DNA binding, sequence-specific DNA binding, sequence-specific DNA binding transcription factor activity, zinc ion binding, nucleus, regulation of cell cycle, intracellular receptor signaling pathway, steroid hormone mediated signaling pathway, steroid hormone receptor activity, regulation of transcription, DNA-templated, neuroblast division, optic lobe placode development, ring gland development, gastrulation, cell fate commitment ...

Distribution of Bandeiraea simplicifolia lectin binding sites in the genital organs of female and male mice<...Distribution of Bandeiraea simplicifolia lectin binding sites in the genital organs of female and male mice<...

Wu TC, Wan Y-JY, Damjanov I. Distribution of Bandeiraea simplicifolia lectin binding sites in the genital organs of female and ... Wu, T. C., Wan, Y-J. Y., & Damjanov, I. (1983). Distribution of Bandeiraea simplicifolia lectin binding sites in the genital ... Distribution of Bandeiraea simplicifolia lectin binding sites in the genital organs of female and male mice. / Wu, T. C.; Wan, ... Wu, T. C. ; Wan, Yu-Jui Yvonne ; Damjanov, I. / Distribution of Bandeiraea simplicifolia lectin binding sites in the genital ...
more infohttps://ucdavis.pure.elsevier.com/en/publications/distribution-of-bandeiraea-simplicifolia-lectin-binding-sites-in-

Ribosome-binding site - WikipediaRibosome-binding site - Wikipedia

A ribosome binding site, or ribosomal binding site (RBS), is a sequence of nucleotides upstream of the start codon of an mRNA ... it is not considered a ribosome binding site.[2][8] Internal ribosome entry site (IRES)[edit]. Eukaryotic ribosomes are known ... 9] Sequences within ribosome binding site affecting messenger RNA translatability and method to direct ribosomes to single ... "Ribosome binding site recognition using neural networks". Genetics and Molecular Biology. 27 (4): 644-650. doi:10.1590/S1415- ...
more infohttps://en.wikipedia.org/wiki/Ribosome_binding_site

16S/18S Binding Sites?16S/18S Binding Sites?

... does anyone know how many binding sites in a single yeast genome (approximately) would bind this probe assuming that it binds ... 16S/18S Binding Sites?. David Singleton dsingle at uga.cc.uga.edu Mon Oct 20 00:05:47 EST 1997 *Previous message: *Free* online ... One of the oligo probes which I am using is described as Universal, and it does indeed bind to yeast genomic DNA (as well as ...
more infohttp://www.bio.net/bionet/mm/yeast/1997-October/007475.html

Large Linear Systems of Binding Sites | SpringerLinkLarge Linear Systems of Binding Sites | SpringerLink

Ben-Naim A. (2001) Large Linear Systems of Binding Sites. In: Cooperativity and Regulation in Biochemical Processes. Springer, ... In this section we introduce the matrix method to rewrite the GPF of a linear system of m sites in a more convenient form. This ... We use cookies to improve your experience with our site. More information Accept. ... Large Eigenvalue Pair Correlation Cyclic System Intrinsic Binding Constant Large Linear System ...
more infohttps://link.springer.com/chapter/10.1007/978-1-4757-3302-0_7

Binding site plan - King CountyBinding site plan - King County

Binding site plan land use permit for unincorporated King County from the King County Department of Permitting and ... A binding site plan provides an alternative method for division of land for commercial and industrial zoned property, mobile ... Affidavit of Correction Alteration Binding site plan Boundary/lot line adjustment Clearing & grading Conditional use Critical ... Refer to the binding site plans packet for application materials *Request an application packet by mail by calling the ...
more infohttps://www.kingcounty.gov/depts/permitting-environmental-review/info/PermitTypes/landuse/binding.aspx

Software for finding transcription factor binding sitesSoftware for finding transcription factor binding sites

... There are many different groups that are developing software for ... A Java application that reuires a local installation of a database that provides binding site information (eg the Public ... finding transciption factor binding sites, alongside our own development of the BIFA tool which forms part of the Apples ...
more infohttps://warwick.ac.uk/fac/sci/moac/people/students/2007/nigel_dyer/phd/bindingsitelocators/

Sodium-Binding Site Types in Proteins | SpringerLinkSodium-Binding Site Types in Proteins | SpringerLink

Cation binding sites and structure-function relations; Na+-dependent proteins Sodium: An alkali metal (Na) with atomic number ... Lev B., Roux B., Noskov S.Y. (2013) Sodium-Binding Site Types in Proteins. In: Kretsinger R.H., Uversky V.N., Permyakov E.A. ( ... Noskov SY, Roux B (2008) Control of ion selectivity in LeuT: two Na+ binding sites with two different mechanisms. J Mol Biol ... Sodium-binding protein: Any protein or enzyme that requires the binding of a sodium ion to its structural stability or ...
more infohttps://link.springer.com/referenceworkentry/10.1007/978-1-4614-1533-6_242

Binding Web Pages with nHydrate - CodeProjectBinding Web Pages with nHydrate - CodeProject

Bind your UI controls to generated objects generically; Author: Christopher R Davis, Ben Traynor; Updated: 1 Jun 2011; Section ... An edit page overrides these methods to add any custom code needed to the bind. Below is a class diagram of my main site ... How you choose to bind or map a user interface is specific, based on your technology such as web forms, MVC, WinForms, etc. You ... In this sample, all fields bind to the same object; however this is not necessary. We could just as easily bind some of the UI ...
more infohttps://www.codeproject.com/Articles/205099/Binding-Web-Pages-with-nHydrate?fid=1630703&df=90&mpp=10&sort=Position&spc=None&tid=4070248

Frontiers | P53 Binding Sites in Transposons | GeneticsFrontiers | P53 Binding Sites in Transposons | Genetics

In line with the latter, recent studies reported existence of p53 binding sites in sequences of primate LTRs3, Alus4,5 and ... one of the reported p53 binding sites was composed of the low complexity repeat. In summary, the original work of el-Deiry et ... it has been observed that many p53 binding sites are species-specific2, indicating that a remarkable flexibility resided in the ... a highly influential paper describing the consensus binding site for the key transcription factor p53 was published in Nature ...
more infohttps://www.frontiersin.org/articles/10.3389/fgene.2012.00040/full

Ankyrin-G binding site (IPR020969) | InterPro | EMBL-EBIAnkyrin-G binding site (IPR020969) | InterPro | EMBL-EBI

InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites ... Ankyrin-G binding site (IPR020969). Short name: Ankyrin-G_BS Description. Interactions with ankyrin-G are crucial to the ... This conserved 9-amino acid motif ((V/A)P(I/L)AXXE(S/D)D) is required for ankyrin-G binding and functions to localise sodium ... Identification of a conserved ankyrin-binding motif in the family of sodium channel alpha subunits.. J. Biol. Chem. 278 27333-9 ...
more infohttp://www.ebi.ac.uk/interpro/entry/IPR020969?q=type:binding_site

Phys.org - binding sitePhys.org - binding site

Phys.org internet news portal provides the latest news on science including: Physics, Space Science, Earth Science, Health and Medicine
more infohttps://phys.org/tags/binding+site/sort/liverank/1w/

Accurate Prediction of Peptide Binding Sites on Protein SurfacesAccurate Prediction of Peptide Binding Sites on Protein Surfaces

We show that spatial atomic position specific scoring matrices of binding sites for each peptide residue can capture the ... important for binding and when used to scan the surface of target proteins can accurately identify candidate binding sites for ... The accurate prediction of protein-peptide binding without prior structural knowledge will ultimately enable better functional ... Here, we present a general approach for predicting protein-peptide interaction sites. ...
more infohttps://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1000335

ZFBS - Zinc Finger Binding Site | AcronymFinderZFBS - Zinc Finger Binding Site | AcronymFinder

ZFBS stands for Zinc Finger Binding Site. ZFBS is defined as Zinc Finger Binding Site very rarely. ... www.acronymfinder.com/Zinc-Finger-Binding-Site-(ZFBS).html. *Chicago style: Acronym Finder. S.v. "ZFBS." Retrieved December 17 ... www.acronymfinder.com/Zinc-Finger-Binding-Site-(ZFBS).html,ZFBS,/a,. ... www.acronymfinder.com/Zinc-Finger-Binding-Site-(ZFBS).html ... www.acronymfinder.com/Zinc-Finger-Binding-Site-(ZFBS).html ...
more infohttps://www.acronymfinder.com/Zinc-Finger-Binding-Site-

I2BS - I2-Imidazoline Binding Site | AcronymFinderI2BS - I2-Imidazoline Binding Site | AcronymFinder

I2BS stands for I2-Imidazoline Binding Site. I2BS is defined as I2-Imidazoline Binding Site very rarely. ... 2019 https://www.acronymfinder.com/I2_Imidazoline-Binding-Site-(I2BS).html. *Chicago style: Acronym Finder. S.v. "I2BS." ... n.d.) Acronym Finder. (2019). Retrieved February 19 2019 from https://www.acronymfinder.com/I2_Imidazoline-Binding-Site-(I2BS). ... a href=https://www.acronymfinder.com/I2_Imidazoline-Binding-Site-(I2BS).html,I2BS,/a,. ...
more infohttps://www.acronymfinder.com/I2_Imidazoline-Binding-Site-

Secondary Structure Preferences of Mn2+ Binding Sites in Bacterial ProteinsSecondary Structure Preferences of Mn2+ Binding Sites in Bacterial Proteins

Amino Acids Involved in Mn2+ Binding. The percentage of aspartic acid residues in Mn2+ binding sites is equal to 34.16%. The ... result in reorganization of binding sites for certain ligands or even in the availability of potential binding sites. ... Mn2+ binding sites which consist of two histidines and a single glutamic or aspartic acid. The percentage of sites with three ... One may think that there should be many Asp-Xaa-Asp-Xaa-Asp-Gly motifs in Mn2+ binding sites; see Table 2. However, this type ...
more infohttps://www.hindawi.com/journals/abi/2014/501841/

Folate binding site of flavin-dependent thymidylate synthase | PNASFolate binding site of flavin-dependent thymidylate synthase | PNAS

Folate binding site of flavin-dependent thymidylate synthase. Eric M. Koehn, Laura L. Perissinotti, Salah Moghram, Arjun ... thought you would like to see the PNAS web site. ... Folate binding site of flavin-dependent thymidylate synthase ... Ultrafast real-time visualization of active site flexibility of flavoenzyme thymidylate synthase ThyX ... and computer modeling shed light on the cofactor binding and function. The unique structural data will likely facilitate ...
more infohttps://www.pnas.org/content/early/2012/09/07/1206077109.abstract

AP endonuclease 1, binding site (IPR020847) | InterPro | EMBL-EBIAP endonuclease 1, binding site (IPR020847) | InterPro | EMBL-EBI

InterPro provides functional analysis of proteins by classifying them into families and predicting domains and important sites ... AP endonuclease 1, binding site (IPR020847). Short name: AP_endonuclease_F1_BS ... This entry represents a motif containing a glutamate residue which has been shown in the Escherichia coli enzyme to bind a ... Amongst these is base-loss which forms apurinic/apyrimidinic (AP) sites or strand breaks with atypical 3 termini. DNA repair ...
more infohttp://www.ebi.ac.uk/interpro/entry/IPR020847

Binding Sites for Amyloid-β Oligomers and Synaptic Toxicity.  - PubMed - NCBIBinding Sites for Amyloid-β Oligomers and Synaptic Toxicity. - PubMed - NCBI

Citations may include links to full-text content from PubMed Central and publisher web sites. ... their binding sites, and species selectivity. Many cell-surface proteins have been reported to bind Aβ. Binding sites for Aβ ... Binding Sites for Amyloid-β Oligomers and Synaptic Toxicity.. Smith LM1, Strittmatter SM1. ... Cellular prion protein (PrPC) is a high-affinity Aβ oligomer binding site, and a range of data delineates a signaling pathway ...
more infohttps://www.ncbi.nlm.nih.gov/pubmed/27940601

Multiple YY1 and CTCF binding sites in im... & related info | MendeleyMultiple YY1 and CTCF binding sites in im... & related info | Mendeley

... contain unusual tandem arrays of DNA-binding sites for transcription factors, including YY1 for the Peg3, Gnas, and Xist/Tsix ... These multiple DNA-binding sites are known to be the only functionally shared and evolutionarily selected feature among these ... We hypothesize that the multiplicity associated with the YY1 and CTCF binding sites may be designed for attracting and ... Known imprinting control regions (ICRs) contain unusual tandem arrays of DNA-binding sites for transcription factors, including ...
more infohttps://www.mendeley.com/research-papers/multiple-yy1-ctcf-binding-sites-imprinting-control-regions/

Bioconductor - Gene Regulation Transcription Factor Binding SitesBioconductor - Gene Regulation Transcription Factor Binding Sites

Finding Candidate Binding Sites for Known Transcription Factors via Sequence Matching. The binding of transcription factor ... Finding Candidate Binding Sites for Known Transcription Factors via Sequence Matching. *From reads to regions: a Bioconductor ... This dataset and our exploration has revealed a number of GATAA binding sites within these tighly co-regulated NCR genes, but ... Sequence-based transcription factor binding site search methods answer two questions:. *For a given TF, what DNA sequence ...
more infohttp://bioconductor.org/help/workflows/gene-regulation-tfbs/

Rug BindingRug Binding

Top20Sites.com is the leading directory of popular Binding Service, Carpet Pullers, Carpet Binding, & Binding Equipment sites. ... Looking for the webs Top Rug Binding Sites? ... Home > Rug Binding Sites > Top Rug Binding Sites. Top Binding ... Carpet Binding Sites , Carpet Binding , Binding Equipment Sites , Binding Equipment , Binding Supplies Sites , Binding Supplies ... Atlanta Carpet Binding - On-site custom cutting, binding, fringing, & carpet base. Atlanta Carpet Binding, On site binding, ...
more infohttps://www.top20sites.com/top-rug-binding-sites

Positional distribution of human transcription factor binding sitesPositional distribution of human transcription factor binding sites

... binding sites using ChIP-chip data, and applied it to recently published experiments on binding sites of nine TFs: OCT4, SOX2, ... We found that for each of the nine TFs the estimated binding site distribution is closely approximated by a mixture of two ... Most GO terms were enriched either among the proximal targets or among those with a uniform distribution of binding sites. For ... whose binding sites belong to the uniform distribution. ... About us Privacy Policy Terms of Use Site Map. Copyright © Ovid ...
more infohttps://insights.ovid.com/nucar/200836210/00006178-200836210-00015

Snowboard Bindings Sites - Top20Sites.comSnowboard Bindings Sites - Top20Sites.com

Looking for Snowboard Bindings Sites? Top20Sites.com is the leading directory of popular Used Snowboards, Discount Snowboards, ... Step-In Snowboard Binding Snowboard Step-In Bindings. Invest in step-in snowboard bindings and step-in binding investment. ... Snowboard Bindings and Binding Reviews : Burton, Ride, Flow, K2.... Welcome to snowboard-bindings.net - Here you can find a ... The Best Snowboard Bindings - 2016 Top Picks & Reviews. Looking for the best snowboard bindings? Here the snowboard bindings ...
more infohttps://www.top20sites.com/items/search.aspx?keyword=snowboard+bindings

Eukaryotic Transcription Factor Binding Sites-modeling and Integrative Search Methods | UMIACSEukaryotic Transcription Factor Binding Sites-modeling and Integrative Search Methods | UMIACS

Eukaryotic Transcription Factor Binding Sites-modeling and Integrative Search Methods. Title. Eukaryotic Transcription Factor ... Current state-of-the-art techniques for improving computational identification of binding sites can be broadly categorized into ... A comprehensive knowledge of transcription factor binding sites (TFBS) is important for a mechanistic understanding of ... aim to improve binding motif models by extracting maximal sequence information from experimentally determined binding sites and ...
more infohttps://www.umiacs.umd.edu/publications/eukaryotic-transcription-factor-binding-sites%E2%80%94modeling-and-integrative-search-methods

Comparative integromics on FZD7 orthologs: Conserved binding site...: Ingenta ConnectComparative integromics on FZD7 orthologs: Conserved binding site...: Ingenta Connect

Comparative genomics analyses revealed that the binding sites for PU.1, SP1/Krüppel-like, CCAAT-box, and TCF/LEF/SOX ... Comparative integromics on FZD7 orthologs: Conserved binding sites for PU.1, SP1, CCAAT-box and TCF/LEF/SOX transcription ... and PDZ-binding motifs. Ser550 and Ser556 of FZD7 orthologs were putative aPKC phosphorylation sites. Dimerization and Ser550/ ... Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. I am Happy with this Find out ...
more infohttps://www.ingentaconnect.com/content/sp/ijmm/2007/00000019/00000003/art00026
  • One of the oligo probes which I am using is described as 'Universal', and it does indeed bind to yeast genomic DNA (as well as mitochondrial, I assume). (bio.net)
  • Methylation and deamination of CpGs generate p53-binding sites on a genomic scale. (frontiersin.org)
  • On the other hand, the percentage of Mn 2+ sites with at least one amino acid in the "beta strand-major binder-random coil" motif of secondary structure (77.88%) does not depend on genomic GC-content. (hindawi.com)
  • Current state-of-the-art techniques for improving computational identification of binding sites can be broadly categorized into two classes: (1) approaches that aim to improve binding motif models by extracting maximal sequence information from experimentally determined binding sites and (2) approaches that supplement binding motif models with additional genomic or other attributes (such as evolutionary conservation). (umd.edu)
  • A ribosome binding site , or ribosomal binding site ( RBS ), is a sequence of nucleotides upstream of the start codon of an mRNA transcript that is responsible for the recruitment of a ribosome during the initiation of protein translation . (wikipedia.org)
  • The ribosomal protein S1 binds to adenine sequences upstream of the RBS. (wikipedia.org)
  • Ribosome recruitment in eukaryotes happens when eukaryote initiation factors elF4F and poly(A)-binding protein (PABP) recognize the 5' capped mRNA and recruit the 43S ribosome complex at that location. (wikipedia.org)
  • This is especially useful when multiple start codons are situated around the potential start site of the protein coding sequence. (wikipedia.org)
  • Any protein or enzyme that requires the binding of a sodium ion to its structural stability or functional activity. (springer.com)
  • In biochemistry, a binding site is a region on a protein or piece of DNA or RNA to which ligands (specific molecules and/or ions) may form a chemical bond. (wikipedia.org)
  • When a binding site of one protein identifies with another protein's surface, a non-covalent bond is formed between the two polypeptide (peptide) chains and a combined new protein is formed. (wikipedia.org)
  • Cellular prion protein (PrP C ) is a high-affinity Aβ oligomer binding site, and a range of data delineates a signaling pathway leading from Aβ complexation with PrP C to neuronal impairment. (nih.gov)
  • A study led by researchers at the UC San Diego Stem Cell Research program and funded by the California Institute for Regenerative Medicine (CIRM) looks at an important RNA binding protein called LIN28, which is implicated in pluripotency and reprogramming as well as in cancer and other diseases. (ucsd.edu)
  • This process, known as autoregulation, helps to maintain a so-called "steady-state" system in which a protein positively regulates its own production by binding to a regulatory element of the mRNA for the gene coding it. (ucsd.edu)
  • The discovery of thousands of precise binding sites for LIN28 within human genes offers a novel look at the role this protein plays in development and disease processes. (ucsd.edu)
  • PocketMatch: a new algorithm to compare binding sites in protein structures. (nih.gov)
  • Inferring functional similarities between protein molecules by comparing their binding sites is still largely exploratory and not as yet a routine protocol. (nih.gov)
  • He produced crystals of concanavalin A complexes with methyl-glucoside and with methyl-mannoside and participated in solving the structure of this protein binding-site for saccharides. (ebooks.com)
  • KCNQ2/KCNQ3 channels are preferentially localised to the surface of axons both at the axonal initial segment and more distally, and this axonal initial segment targeting of surface KCNQ channels is mediated by these ankyrin-G binding motifs of KCNQ2 and KCNQ3 [ PMID: 16735477 ]. (ebi.ac.uk)
  • As to Zn 2+ binding 3D structural motifs, Sri Krishna et al. (hindawi.com)
  • That is why the knowledge on preferable secondary structural motifs around each of the amino acid residues may be even more helpful for prediction of ion binding sites than the knowledge on the 3D structural motifs for the complete coordination spheres. (hindawi.com)
  • ribosome binding, mRNA processing, and transcription termination are also signaled by these sequence motifs. (wikipedia.org)
  • In any case, does anyone know how many binding sites in a single yeast genome (approximately) would bind this probe assuming that it binds rRNA? (bio.net)
  • All of these binding sites could be uniquely mapped to the reference human genome sequence (hg19). (frontiersin.org)
  • Waves of retrotransposon expansion remodel genome organization and CTCF binding in multiple mammalian lineages. (frontiersin.org)
  • The data were obtained from a genome-wide coverage of promoter regions from 8-kb upstream of the transcription start site (TSS) to 2-kb downstream. (ovid.com)
  • Using genome-wide biochemical methods to look at the set of all RNA molecules across the transcriptome, the researchers found that LIN28 recognizes and binds to a known hairpin-like structure found on the let-7 family of miRNA, but surprisingly, this same structure is also found on mRNAs, allowing LIN28 to directly regulate thousands of targets. (ucsd.edu)
  • The identification of transcription factor binding sites (TFBS) is an important initial step in determining the DNA signals that regulate transcription of the genome. (umd.edu)
  • These identification methods all attempt to filter the quantity of TFBS identified by aligning positional weight matrices that describe the binding site and employ either (i) a P-value threshold for accepting a site, (ii) an over-representation measure of neighboring sites, or (iii) conservation with the mouse genome and application of P-value thresholds. (umd.edu)
  • There are, however, several private and public databases devoted to compilation of experimentally reported, and sometimes computationally predicted, binding sites for different transcription factors in different organisms. (wikipedia.org)
  • Additionally, we find that only half of the 481 experimentally mapped sites can be found in sequence regions conserved with mouse, but the predictive power of the binding site identification method is up to threefold higher in the conserved regions. (umd.edu)
  • Noskov SY, Roux B (2008) Control of ion selectivity in LeuT: two Na + binding sites with two different mechanisms. (springer.com)
  • Putative receptors for Aβ, their binding sites, and species selectivity. (nih.gov)
  • Beta strands near Mn 2+ binding residues should be stable because they are enriched by such beta formers as valine and isoleucine, as well as by specific combinations of hydrophobic and hydrophilic amino acid residues characteristic to beta sheet. (hindawi.com)
  • 1 ], there are three amino acid residues most frequently found in Mn 2+ binding sites: His, Asp, and Glu. (hindawi.com)
  • Histidine has the highest normalized frequency in binding sites, while glutamic acid has the lowest normalized frequency among those three amino acid residues [ 1 ]. (hindawi.com)
  • 4 ) postulated that dsRNA might bind at one or both of two patches of positively charged residues on the glycan-free face of the TLR3-ECD. (pnas.org)
  • We noted the presence of two sulfate molecules from the crystallization medium stably bound to residues in LRRs 12 and 20, the two LRRs that contain large insertions ( 3 ). (pnas.org)
  • First described by Martin and his colleagues (1976) to account for the behavioral effects of selected benzomorphan opiates, sigma binding sites were originally classified as an opioid receptor subtype. (springer.com)
  • 1985). In addition, the (+) isomers of opiates such as pentazocine and N-allylnormetazocine (SKF 10,047) are more active at sigma binding sites, while opiate receptors are typically more responsive to (-) isomers (Weber et al. (springer.com)
  • The opiates bind to opiate receptors that are concentrated in areas within the reward system. (drugabuse.gov)
  • PSFM are usually conceived with the implicit assumption of positional independence (different positions at the DNA binding site contribute independently to the site function), although this assumption has been disputed for some DNA binding sites. (wikipedia.org)
  • We developed a method for estimating the positional distribution of transcription factor (TF) binding sites using ChIP-chip data, and applied it to recently published experiments on binding sites of nine TFs: OCT4, SOX2, NANOG, HNF1A, HNF4A, HNF6, FOXA2, USF1 and CREB1. (ovid.com)
  • Studying embryonic stem cells and somatic cells stably expressing LIN28, the researchers defined discrete binding sites of LIN28 in 25 percent of human transcripts. (ucsd.edu)
  • Subsequent work suggested this designation was inaccurate since, unlike opioid receptors, the sigma site is insensitive to blockade by naloxone (Itzhak et al. (springer.com)
  • Chromatin remodeling, methylation, histone modification, chromosome interaction, distal enhancers, and the cooperative binding of transcription co-factors all play an important role. (bioconductor.org)
  • Binding Sites for Amyloid-β Oligomers and Synaptic Toxicity. (nih.gov)
  • Binding sites for Aβ monomers or oligomers are indicated with arrows when specific sites are known to mediate binding or with brackets when less information is available. (nih.gov)
  • This is a very simple model used to demonstrate how to can bind objects with associations. (codeproject.com)
  • In this workflow we demonstrate Bioconductor techniques for finding candidate TF binding sites in DNA sequence using the model organism Saccharomyces cerevisiae. (bioconductor.org)
  • Though the representation used is conceptually simplistic, we demonstrate that along with the new alignment strategy used, it is sufficient to enable binding comparison with high sensitivity. (nih.gov)
  • Here we present X-ray crystal structures of FDTS with several folate derivatives, which together with mutagenesis, kinetic analysis, and computer modeling shed light on the cofactor binding and function. (pnas.org)
  • A more accurate way of representing binding sites is through Position Specific Frequency Matrices (PSFM). (wikipedia.org)
  • These mutations locate the dsRNA binding site on the glycan-free, lateral surface of TLR3 toward the C terminus and suggest a model for dsRNA binding and TLR3 activation. (pnas.org)
  • A Java application that reuires a local installation of a database that provides binding site information (eg the Public Transfac 6.0 data). (warwick.ac.uk)
  • We will see how to create prompts and validators, as well as bind data to controls in a compile-time checked manner. (codeproject.com)
  • Though in recent years many new kinds of data have become available for identifying transcription factor binding sites (TFBSs) - ChIP-seq and DNase I hypersensitivity regions among them - sequence matching continues to play an important role. (bioconductor.org)
  • Ingenta Connect website makes use of cookies so as to keep track of data that you have filled in. (ingentaconnect.com)
  • To benefit from the enormous amount of structural data that is being rapidly accumulated, it is essential to have high throughput tools that enable large scale binding site comparison. (nih.gov)
  • We have demonstrated that TLR3-ECD binds directly to short dsRNA and polyinosinic-polycytidylic acid (pI:pC), a dsRNA surrogate ( 3 ). (pnas.org)
  • We will see, however, that even this small collection of co-regulated genes of similar function exhibits considerable regulatory complexity, with (among other things) activators and repressors competing to bind to the same DNA promoter sequence. (bioconductor.org)
  • We presume, following Allocco, that such correlation among genes, including one transcription factor, is a plausible place to look for shared transcription factor binding sites. (bioconductor.org)
  • For example, the three stemness-related TFs have several hundred target genes that belong to 'development' and 'morphogenesis' whose binding sites belong to the uniform distribution. (ovid.com)
  • The sorted arrays are then aligned using an incremental alignment method and scored to obtain PMScores for pairs of sites. (nih.gov)
  • Impact of Alu repeats on the evolution of human p53 binding sites. (frontiersin.org)
  • Additionally, we found that one of the early reported p53 binding sites is composed of a low-complexity repeat. (frontiersin.org)
  • Karbon, E.W. and Naper, K., 1990, Chronic haloperidol administration differentially regulates [3H] DTG and [3H] (+)-3-PPP labeled sigma binding sites in guinea pig brain membranes. (springer.com)
  • Buy Instabind DIY Binding Tapes, Carpet Binding and Serging Equipment, Rugmaking supplies and tools, direct from Bond Products. (top20sites.com)
  • One of the main reasons for this is the limitation in the choice of appropriate analytical tools that can compare binding sites with high sensitivity. (nih.gov)
  • An edit page overrides these methods to add any custom code needed to the bind. (codeproject.com)
  • However, the development of DNA microarrays and fast sequencing techniques has led to new, massively parallel methods for in-vivo identification of binding sites, such as ChIP-chip and ChIP-Seq. (wikipedia.org)
  • Most GO terms were enriched either among the proximal targets or among those with a uniform distribution of binding sites. (ovid.com)
  • Comparative genomics analyses revealed that the binding sites for PU.1, SP1/Krüppel-like, CCAAT-box, and TCF/LEF/SOX transcription factors were conserved among 5'-promoter regions of mammalian FZD7 orthologs. (ingentaconnect.com)
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  • But we now see that LIN28 can, in essence, bypass let-7 and find many, many other binding sites - perhaps with the same adverse effect of uncontrolled cell overgrowth," said Yeo. (ucsd.edu)