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.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.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.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.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.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.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.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.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.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.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.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.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.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).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.Mutation, Missense: A mutation in which a codon is mutated to one directing the incorporation of a different amino acid. This substitution may result in an inactive or unstable product. (From A Dictionary of Genetics, King & Stansfield, 5th ed)Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Kinetics: The rate dynamics in chemical or physical systems.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.Cell Line: Established cell cultures that have the potential to propagate indefinitely.DNA Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Evolution, Molecular: The process of cumulative change at the level of DNA; RNA; and PROTEINS, over successive generations.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.Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.Genetic Variation: Genotypic differences observed among individuals in a population.Bacterial Proteins: Proteins found in any species of bacterium.Codon: A set of three nucleotides in a protein coding sequence that specifies individual amino acids or a termination signal (CODON, TERMINATOR). Most codons are universal, but some organisms do not produce the transfer RNAs (RNA, TRANSFER) complementary to all codons. These codons are referred to as unassigned codons (CODONS, NONSENSE).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.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.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.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.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.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.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.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).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.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.Alanine: A non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases IMMUNITY, and provides energy for muscle tissue, BRAIN, and the CENTRAL NERVOUS SYSTEM.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Alleles: Variant forms of the same gene, occupying the same locus on homologous CHROMOSOMES, and governing the variants in production of the same gene product.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.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.Amino Acids, Essential: Amino acids that are not synthesized by the human body in amounts sufficient to carry out physiological functions. They are obtained from dietary foodstuffs.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.Restriction Mapping: Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.Glycine: A non-essential amino acid. It is found primarily in gelatin and silk fibroin and used therapeutically as a nutrient. It is also a fast inhibitory neurotransmitter.Leucine: An essential branched-chain amino acid important for hemoglobin formation.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.Viral Proteins: Proteins found in any species of virus.Amino Acid Transport Systems: Cellular proteins and protein complexes that transport amino acids across biological membranes.Aspartic Acid: One of the non-essential amino acids commonly occurring in the L-form. It is found in animals and plants, especially in sugar cane and sugar beets. It may be a neurotransmitter.Genes, Bacterial: The functional hereditary units of BACTERIA.Proline: A non-essential amino acid that is synthesized from GLUTAMIC ACID. It is an essential component of COLLAGEN and is important for proper functioning of joints and tendons.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.Enzyme Stability: The extent to which an enzyme retains its structural conformation or its activity when subjected to storage, isolation, and purification or various other physical or chemical manipulations, including proteolytic enzymes and heat.Lysine: An essential amino acid. It is often added to animal feed.Arginine: An essential amino acid that is physiologically active in the L-form.Cysteine: A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.Sequence Deletion: Deletion of sequences of nucleic acids from the genetic material of an individual.Cricetinae: A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.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.Isoleucine: An essential branched-chain aliphatic amino acid found in many proteins. It is an isomer of LEUCINE. It is important in hemoglobin synthesis and regulation of blood sugar and energy levels.Mutant Proteins: Proteins produced from GENES that have acquired MUTATIONS.Valine: A branched-chain essential amino acid that has stimulant activity. It promotes muscle growth and tissue repair. It is a precursor in the penicillin biosynthetic pathway.Epitopes: Sites on an antigen that interact with specific antibodies.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.DNA, Bacterial: Deoxyribonucleic acid that makes up the genetic material of bacteria.Polymorphism, Genetic: The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Escherichia coli Proteins: Proteins obtained from ESCHERICHIA COLI.Selection, Genetic: Differential and non-random reproduction of different genotypes, operating to alter the gene frequencies within a population.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.Viral Envelope Proteins: Layers of protein which surround the capsid in animal viruses with tubular nucleocapsids. The envelope consists of an inner layer of lipids and virus specified proteins also called membrane or matrix proteins. The outer layer consists of one or more types of morphological subunits called peplomers which project from the viral envelope; this layer always consists of glycoproteins.Genes: A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms.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.Virus Replication: The process of intracellular viral multiplication, consisting of the synthesis of PROTEINS; NUCLEIC ACIDS; and sometimes LIPIDS, and their assembly into a new infectious particle.Serine: A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.Sequence Analysis, Protein: A process that includes the determination of AMINO ACID SEQUENCE of a protein (or peptide, oligopeptide or peptide fragment) and the information analysis of the sequence.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).)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.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.Cercopithecus aethiops: A species of CERCOPITHECUS containing three subspecies: C. tantalus, C. pygerythrus, and C. sabeus. They are found in the forests and savannah of Africa. The African green monkey (C. pygerythrus) is the natural host of SIMIAN IMMUNODEFICIENCY VIRUS and is used in AIDS research.Protein Engineering: Procedures by which protein structure and function are changed or created in vitro by altering existing or synthesizing new structural genes that direct the synthesis of proteins with sought-after properties. Such procedures may include the design of MOLECULAR MODELS of proteins using COMPUTER GRAPHICS or other molecular modeling techniques; site-specific mutagenesis (MUTAGENESIS, SITE-SPECIFIC) of existing genes; and DIRECTED MOLECULAR EVOLUTION techniques to create new genes.Phenylalanine: An essential aromatic amino acid that is a precursor of MELANIN; DOPAMINE; noradrenalin (NOREPINEPHRINE), and THYROXINE.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.Asparagine: A non-essential amino acid that is involved in the metabolic control of cell functions in nerve and brain tissue. It is biosynthesized from ASPARTIC ACID and AMMONIA by asparagine synthetase. (From Concise Encyclopedia Biochemistry and Molecular Biology, 3rd ed)Threonine: An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.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.Glutamine: A non-essential amino acid present abundantly throughout the body and is involved in many metabolic processes. It is synthesized from GLUTAMIC ACID and AMMONIA. It is the principal carrier of NITROGEN in the body and is an important energy source for many cells.Genotype: The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.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.Molecular Weight: The sum of the weight of all the atoms in a molecule.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.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.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.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Amino Acids, Aromatic: Amino acids containing an aromatic side chain.Histidine: An essential amino acid that is required for the production of HISTAMINE.Capsid Proteins: Proteins that form the CAPSID of VIRUSES.DNA Gyrase: A bacterial DNA topoisomerase II that catalyzes ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. Gyrase binds to DNA as a heterotetramer consisting of two A and two B subunits. In the presence of ATP, gyrase is able to convert the relaxed circular DNA duplex into a superhelix. In the absence of ATP, supercoiled DNA is relaxed by DNA gyrase.Genetic Complementation Test: A test used to determine whether or not complementation (compensation in the form of dominance) will occur in a cell with a given mutant phenotype when another mutant genome, encoding the same mutant phenotype, is introduced into that cell.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)Protein Folding: Processes involved in the formation of TERTIARY PROTEIN STRUCTURE.Suppression, Genetic: Mutation process that restores the wild-type PHENOTYPE in an organism possessing a mutationally altered GENOTYPE. The second "suppressor" mutation may be on a different gene, on the same gene but located at a distance from the site of the primary mutation, or in extrachromosomal genes (EXTRACHROMOSOMAL INHERITANCE).Pedigree: The record of descent or ancestry, particularly of a particular condition or trait, indicating individual family members, their relationships, and their status with respect to the trait or condition.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.Virulence: The degree of pathogenicity within a group or species of microorganisms or viruses as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host. The pathogenic capacity of an organism is determined by its VIRULENCE FACTORS.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.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.Capsid: The outer protein protective shell of a virus, which protects the viral nucleic acid.Sequence Analysis: A multistage process that includes the determination of a sequence (protein, carbohydrate, etc.), its fragmentation and analysis, and the interpretation of the resulting sequence information.Amino Acids, Branched-Chain: Amino acids which have a branched carbon chain.HIV-1: The type species of LENTIVIRUS and the etiologic agent of AIDS. It is characterized by its cytopathic effect and affinity for the T4-lymphocyte.Gene Library: A large collection of DNA fragments cloned (CLONING, MOLECULAR) from a given organism, tissue, organ, or cell type. It may contain complete genomic sequences (GENOMIC LIBRARY) or complementary DNA sequences, the latter being formed from messenger RNA and lacking intron sequences.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.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.Biological Transport: The movement of materials (including biochemical substances and drugs) through a biological system at the cellular level. The transport can be across cell membranes and epithelial layers. It also can occur within intracellular compartments and extracellular compartments.Open Reading Frames: A sequence of successive nucleotide triplets that are read as CODONS specifying AMINO ACIDS and begin with an INITIATOR CODON and end with a stop codon (CODON, TERMINATOR).Methionine: A sulfur-containing essential L-amino acid that is important in many body functions.Cyanogen Bromide: Cyanogen bromide (CNBr). A compound used in molecular biology to digest some proteins and as a coupling reagent for phosphoroamidate or pyrophosphate internucleotide bonds in DNA duplexes.Amino Acids, SulfurCrystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Transcription Factors: Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.Genes, Viral: The functional hereditary units of VIRUSES.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.Fungal Proteins: Proteins found in any species of fungus.Protein Processing, Post-Translational: Any of various enzymatically catalyzed post-translational modifications of PEPTIDES or PROTEINS in the cell of origin. These modifications include carboxylation; HYDROXYLATION; ACETYLATION; PHOSPHORYLATION; METHYLATION; GLYCOSYLATION; ubiquitination; oxidation; proteolysis; and crosslinking and result in changes in molecular weight and electrophoretic motility.Biological Evolution: The process of cumulative change over successive generations through which organisms acquire their distinguishing morphological and physiological characteristics.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.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)Directed Molecular Evolution: The techniques used to produce molecules exhibiting properties that conform to the demands of the experimenter. These techniques combine methods of generating structural changes with methods of selection. They are also used to examine proposed mechanisms of evolution under in vitro selection conditions.Genome, Viral: The complete genetic complement contained in a DNA or RNA molecule in a virus.Protein PrecursorsAntibodies, Monoclonal: Antibodies produced by a single clone of cells.Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer.Drug Resistance, Microbial: The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Protein Biosynthesis: The biosynthesis of PEPTIDES and PROTEINS on RIBOSOMES, directed by MESSENGER RNA, via TRANSFER RNA that is charged with standard proteinogenic AMINO ACIDS.Chromosome Mapping: Any method used for determining the location of and relative distances between genes on a chromosome.DNA, Viral: Deoxyribonucleic acid that makes up the genetic material of viruses.Viral Nonstructural Proteins: Proteins encoded by a VIRAL GENOME that are produced in the organisms they infect, but not packaged into the VIRUS PARTICLES. Some of these proteins may play roles within the infected cell during VIRUS REPLICATION or act in regulation of virus replication or VIRUS ASSEMBLY.Microbial Sensitivity Tests: Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses).Cell Membrane: The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.Glutamic Acid: A non-essential amino acid naturally occurring in the L-form. Glutamic acid is the most common excitatory neurotransmitter in the CENTRAL NERVOUS SYSTEM.Plant Proteins: Proteins found in plants (flowers, herbs, shrubs, trees, etc.). The concept does not include proteins found in vegetables for which VEGETABLE PROTEINS is available.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.RNA, Viral: Ribonucleic acid that makes up the genetic material of viruses.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.Endopeptidases: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.Protein Sorting Signals: Amino acid sequences found in transported proteins that selectively guide the distribution of the proteins to specific cellular compartments.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.Oligopeptides: Peptides composed of between two and twelve amino acids.Hemagglutinin Glycoproteins, Influenza Virus: Membrane glycoproteins from influenza viruses which are involved in hemagglutination, virus attachment, and envelope fusion. Fourteen distinct subtypes of HA glycoproteins and nine of NA glycoproteins have been identified from INFLUENZA A VIRUS; no subtypes have been identified for Influenza B or Influenza C viruses.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.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.beta-Lactamases: Enzymes found in many bacteria which catalyze the hydrolysis of the amide bond in the beta-lactam ring. Well known antibiotics destroyed by these enzymes are penicillins and cephalosporins.Tyrosine: A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.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.Receptors, Virus: Specific molecular components of the cell capable of recognizing and interacting with a virus, and which, after binding it, are capable of generating some signal that initiates the chain of events leading to the biological response.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.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)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.Blotting, Southern: A method (first developed by E.M. Southern) for detection of DNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.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)Hydrophobic and Hydrophilic Interactions: The thermodynamic interaction between a substance and WATER.Multigene Family: A set of genes descended by duplication and variation from some ancestral gene. Such genes may be clustered together on the same chromosome or dispersed on different chromosomes. Examples of multigene families include those that encode the hemoglobins, immunoglobulins, histocompatibility antigens, actins, tubulins, keratins, collagens, heat shock proteins, salivary glue proteins, chorion proteins, cuticle proteins, yolk proteins, and phaseolins, as well as histones, ribosomal RNA, and transfer RNA genes. The latter three are examples of reiterated genes, where hundreds of identical genes are present in a tandem array. (King & Stanfield, A Dictionary of Genetics, 4th ed)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).Hot Temperature: Presence of warmth or heat or a temperature notably higher than an accustomed norm.Adaptation, Biological: Changes in biological features that help an organism cope with its ENVIRONMENT. These changes include physiological (ADAPTATION, PHYSIOLOGICAL), phenotypic and genetic changes.Glycosylation: The chemical or biochemical addition of carbohydrate or glycosyl groups to other chemicals, especially peptides or proteins. Glycosyl transferases are used in this biochemical reaction.Hemoglobins, Abnormal: Hemoglobins characterized by structural alterations within the molecule. The alteration can be either absence, addition or substitution of one or more amino acids in the globin part of the molecule at selected positions in the polypeptide chains.Sequence Homology: The degree of similarity between sequences. Studies of AMINO ACID SEQUENCE HOMOLOGY and NUCLEIC ACID SEQUENCE HOMOLOGY provide useful information about the genetic relatedness of genes, gene products, and species.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Polymorphism, Single-Stranded Conformational: Variation in a population's DNA sequence that is detected by determining alterations in the conformation of denatured DNA fragments. Denatured DNA fragments are allowed to renature under conditions that prevent the formation of double-stranded DNA and allow secondary structure to form in single stranded fragments. These fragments are then run through polyacrylamide gels to detect variations in the secondary structure that is manifested as an alteration in migration through the gels.Recombination, Genetic: Production of new arrangements of DNA by various mechanisms such as assortment and segregation, CROSSING OVER; GENE CONVERSION; GENETIC TRANSFORMATION; GENETIC CONJUGATION; GENETIC TRANSDUCTION; or mixed infection of viruses.Drug Resistance, Viral: The ability of viruses to resist or to become tolerant to chemotherapeutic agents or antiviral agents. This resistance is acquired through gene mutation.Protein Denaturation: Disruption of the non-covalent bonds and/or disulfide bonds responsible for maintaining the three-dimensional shape and activity of the native protein.Antigens, Viral: Substances elaborated by viruses that have antigenic activity.Epitope Mapping: Methods used for studying the interactions of antibodies with specific regions of protein antigens. Important applications of epitope mapping are found within the area of immunochemistry.Gene Expression Regulation, Bacterial: Any of the processes by which cytoplasmic or intercellular factors influence the differential control of gene action in bacteria.Viral Structural Proteins: Viral proteins that are components of the mature assembled VIRUS PARTICLES. They may include nucleocapsid core proteins (gag proteins), enzymes packaged within the virus particle (pol proteins), and membrane components (env proteins). These do not include the proteins encoded in the VIRAL GENOME that are produced in infected cells but which are not packaged in the mature virus particle,i.e. the so called non-structural proteins (VIRAL NONSTRUCTURAL PROTEINS).Swine: Any of various animals that constitute the family Suidae and comprise stout-bodied, short-legged omnivorous mammals with thick skin, usually covered with coarse bristles, a rather long mobile snout, and small tail. Included are the genera Babyrousa, Phacochoerus (wart hogs), and Sus, the latter containing the domestic pig (see SUS SCROFA).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.Anti-Bacterial Agents: Substances that reduce the growth or reproduction of BACTERIA.Genes, Fungal: The functional hereditary units of FUNGI.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.Serial Passage: Inoculation of a series of animals or in vitro tissue with an infectious bacterium or virus, as in VIRULENCE studies and the development of vaccines.Blotting, Northern: Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.Viral Plaque Assay: Method for measuring viral infectivity and multiplication in CULTURED CELLS. Clear lysed areas or plaques develop as the VIRAL PARTICLES are released from the infected cells during incubation. With some VIRUSES, the cells are killed by a cytopathic effect; with others, the infected cells are not killed but can be detected by their hemadsorptive ability. Sometimes the plaque cells contain VIRAL ANTIGENS which can be measured by IMMUNOFLUORESCENCE.Amino Acids, Basic: Amino acids with side chains that are positively charged at physiological pH.Genes, Dominant: Genes that influence the PHENOTYPE both in the homozygous and the heterozygous state.Amino Acid Transport Systems, Basic: Amino acid transporter systems capable of transporting basic amino acids (AMINO ACIDS, BASIC).Protein Stability: The ability of a protein to retain its structural conformation or its activity when subjected to physical or chemical manipulations.Hemagglutinins, Viral: Specific hemagglutinin subtypes encoded by VIRUSES.Vero Cells: A CELL LINE derived from the kidney of the African green (vervet) monkey, (CERCOPITHECUS AETHIOPS) used primarily in virus replication studies and plaque assays.Neutralization Tests: The measurement of infection-blocking titer of ANTISERA by testing a series of dilutions for a given virus-antiserum interaction end-point, which is generally the dilution at which tissue cultures inoculated with the serum-virus mixtures demonstrate cytopathology (CPE) or the dilution at which 50% of test animals injected with serum-virus mixtures show infectivity (ID50) or die (LD50).Membrane Transport Proteins: Membrane proteins whose primary function is to facilitate the transport of molecules across a biological membrane. Included in this broad category are proteins involved in active transport (BIOLOGICAL TRANSPORT, ACTIVE), facilitated transport and ION CHANNELS.

Cytochrome P450 monooxygenases and insecticide resistance in insects. (1/16550)

Cytochrome P450 monooxygenases are involved in many cases of resistance of insects to insecticides. Resistance has long been associated with an increase in monooxygenase activities and with an increase in cytochrome P450 content. However, this increase does not always account for all of the resistance. In Drosophila melanogaster, we have shown that the overproduction of cytochrome P450 can be lost by the fly without a corresponding complete loss of resistance. These results prompted the sequencing of a cytochrome P450 candidate for resistance in resistant and susceptible flies. Several mutations leading to amino-acid substitutions have been detected in the P450 gene CYP6A2 of a resistant strain. The location of these mutations in a model of the 3D structure of the CYP6A2 protein suggested that some of them may be important for enzyme activity of this molecule. This has been verified by heterologous expression of wild-type and mutated cDNA in Escherichia coli. When other resistance mechanisms are considered, relatively few genetic mutations are involved in insecticide resistance, and this has led to an optimistic view of the management of resistance. Our observations compel us to survey in more detail the genetic diversity of cytochrome P450 genes and alleles involved in resistance.  (+info)

An antiviral mechanism of nitric oxide: inhibition of a viral protease. (2/16550)

Although nitric oxide (NO) kills or inhibits the replication of a variety of intracellular pathogens, the antimicrobial mechanisms of NO are unknown. Here, we identify a viral protease as a target of NO. The life cycle of many viruses depends upon viral proteases that cleave viral polyproteins into individual polypeptides. NO inactivates the Coxsackievirus protease 3C, an enzyme necessary for the replication of Coxsackievirus. NO S-nitrosylates the cysteine residue in the active site of protease 3C, inhibiting protease activity and interrupting the viral life cycle. Substituting a serine residue for the active site cysteine renders protease 3C resistant to NO inhibition. Since cysteine proteases are critical for virulence or replication of many viruses, bacteria, and parasites, S-nitrosylation of pathogen cysteine proteases may be a general mechanism of antimicrobial host defenses.  (+info)

Functional consequences of mutations in the human alpha1A calcium channel subunit linked to familial hemiplegic migraine. (3/16550)

Mutations in alpha1A, the pore-forming subunit of P/Q-type calcium channels, are linked to several human diseases, including familial hemiplegic migraine (FHM). We introduced the four missense mutations linked to FHM into human alpha1A-2 subunits and investigated their functional consequences after expression in human embryonic kidney 293 cells. By combining single-channel and whole-cell patch-clamp recordings, we show that all four mutations affect both the biophysical properties and the density of functional channels. Mutation R192Q in the S4 segment of domain I increased the density of functional P/Q-type channels and their open probability. Mutation T666M in the pore loop of domain II decreased both the density of functional channels and their unitary conductance (from 20 to 11 pS). Mutations V714A and I1815L in the S6 segments of domains II and IV shifted the voltage range of activation toward more negative voltages, increased both the open probability and the rate of recovery from inactivation, and decreased the density of functional channels. Mutation V714A decreased the single-channel conductance to 16 pS. Strikingly, the reduction in single-channel conductance induced by mutations T666M and V714A was not observed in some patches or periods of activity, suggesting that the abnormal channel may switch on and off, perhaps depending on some unknown factor. Our data show that the FHM mutations can lead to both gain- and loss-of-function of human P/Q-type calcium channels.  (+info)

Phe161 and Arg166 variants of p-hydroxybenzoate hydroxylase. Implications for NADPH recognition and structural stability. (4/16550)

Phe161 and Arg166 of p-hydroxybenzoate hydroxylase from Pseudomonas fluorescens belong to a newly discovered sequence motif in flavoprotein hydroxylases with a putative dual function in FAD and NADPH binding [1]. To study their role in more detail, Phe161 and Arg166 were selectively changed by site-directed mutagenesis. F161A and F161G are catalytically competent enzymes having a rather poor affinity for NADPH. The catalytic properties of R166K are similar to those of the native enzyme. R166S and R166E show impaired NADPH binding and R166E has lost the ability to bind FAD. The crystal structure of substrate complexed F161A at 2.2 A is indistinguishable from the native enzyme, except for small changes at the site of mutation. The crystal structure of substrate complexed R166S at 2.0 A revealed that Arg166 is important for providing an intimate contact between the FAD binding domain and a long excursion of the substrate binding domain. It is proposed that this interaction is essential for structural stability and for the recognition of the pyrophosphate moiety of NADPH.  (+info)

Possible role for ligand binding of histidine 81 in the second transmembrane domain of the rat prostaglandin F2alpha receptor. (5/16550)

For the five principal prostanoids PGD2, PGE2, PGF2alpha, prostacyclin and thromboxane A2 eight receptors have been identified that belong to the family of G-protein-coupled receptors. They display an overall homology of merely 30%. However, single amino acids in the transmembrane domains such as an Arg in the seventh transmembrane domain are highly conserved. This Arg has been identified as part of the ligand binding pocket. It interacts with the carboxyl group of the prostanoid. The aim of the current study was to analyze the potential role in ligand binding of His-81 in the second transmembrane domain of the rat PGF2alpha receptor, which is conserved among all PGF2alpha receptors from different species. Molecular modeling suggested that this residue is located in close proximity to the ligand binding pocket Arg 291 in the 7th transmembrane domain. The His81 (H) was exchanged by site-directed mutagenesis to Gln (Q), Asp (D), Arg (R), Ala (A) and Gly (G). The receptor molecules were N-terminally extended by a Flag epitope for immunological detection. All mutant proteins were expressed at levels between 50% and 80% of the wild type construct. The H81Q and H81D receptor bound PGF2alpha with 2-fold and 25-fold lower affinity, respectively, than the wild type receptor. Membranes of cells expressing the H81R, H81A or H81G mutants did not bind significant amounts of PGF2alpha. Wild type receptor and H81Q showed a shallow pH optimum for PGF2alpha binding around pH 5.5 with almost no reduction of binding at higher pH. In contrast the H81D mutant bound PGF2alpha with a sharp optimum at pH 4.5, a pH at which the Asp side chain is partially undissociated and may serve as a hydrogen bond donor as do His and Gln at higher pH values. The data indicate that the His-81 in the second transmembrane domain of the PGF2alpha receptor in concert with Arg-291 in the seventh transmembrane domain may be involved in ligand binding, most likely not by ionic interaction with the prostaglandin's carboxyl group but rather as a hydrogen bond donor.  (+info)

The contribution of adjacent subunits to the active sites of D-3-phosphoglycerate dehydrogenase. (6/16550)

D-3-Phosphoglycerate dehydrogenase (PGDH) from Escherichia coli is allosterically inhibited by L-serine, the end product of its metabolic pathway. Previous results have shown that inhibition by serine has a large effect on Vmax and only a small or negligible effect on Km. PGDH is thus classified as a V-type allosteric enzyme. In this study, the active site of PGDH has been studied by site-directed mutagenesis to assess the role of certain residues in substrate binding and catalysis. These consist of a group of cationic residues (Arg-240, Arg-60, Arg-62, Lys-39, and Lys-141') that potentially form an electrostatic environment for the binding of the negatively charged substrate, as well as the only tryptophan residue found in PGDH and which fits into a hydrophobic pocket immediately adjacent to the active site histidine residue. Interestingly, Trp-139' and Lys-141' are part of the polypeptide chain of the subunit that is adjacent to the active site. The results of mutating these residues show that Arg-240, Arg-60, Arg-62, and Lys-141' play distinct roles in the binding of the substrate to the active site. Mutants of Trp-139' show that this residue may play a role in stabilizing the catalytic center of the enzyme. Furthermore, these mutants appear to have a significant effect on the cooperativity of serine inhibition and suggest a possible role for Trp-139' in the cooperative interactions between subunits.  (+info)

Mechanistic studies on the reductive half-reaction of NADPH-cytochrome P450 oxidoreductase. (7/16550)

Site-directed mutagenesis has been employed to study the mechanism of hydride transfer from NADPH to NADPH-cytochrome P450 oxidoreductase. Specifically, Ser457, Asp675, and Cys630 have been selected because of their proximity to the isoalloxazine ring of FAD. Substitution of Asp675 with asparagine or valine decreased cytochrome c reductase activities 17- and 677-fold, respectively, while the C630A substitution decreased enzymatic activity 49-fold. Earlier studies had shown that the S457A mutation decreased cytochrome c reductase activity 90-fold and also lowered the redox potential of the FAD semiquinone (Shen, A., and Kasper, C. B. (1996) Biochemistry 35, 9451-9459). The S457A/D675N and S457A/D675N/C630A mutants produced roughly multiplicative decreases in cytochrome c reductase activity (774- and 22000-fold, respectively) with corresponding decreases in the rates of flavin reduction. For each mutation, increases were observed in the magnitudes of the primary deuterium isotope effects with NADPD, consistent with decreased rates of hydride transfer from NADPH to FAD and an increase in the relative rate limitation of hydride transfer. Asp675 substitutions lowered the redox potential of the FAD semiquinone. In addition, the C630A substitution shifted the pKa of an ionizable group previously identified as necessary for catalysis (Sem, D. S., and Kasper, C. B. (1993) Biochemistry 32, 11539-11547) from 6.9 to 7.8. These results are consistent with a model in which Ser457, Asp675, and Cys630 stabilize the transition state for hydride transfer. Ser457 and Asp675 interact to stabilize both the transition state and the FAD semiquinone, while Cys630 interacts with the nicotinamide ring and the fully reduced FAD, functioning as a proton donor/acceptor to FAD.  (+info)

Cystic fibrosis-associated mutations at arginine 347 alter the pore architecture of CFTR. Evidence for disruption of a salt bridge. (8/16550)

Arginine 347 in the sixth transmembrane domain of cystic fibrosis transmembrane conductance regulator (CFTR) is a site of four cystic fibrosis-associated mutations. To better understand the function of Arg-347 and to learn how mutations at this site disrupt channel activity, we mutated Arg-347 to Asp, Cys, Glu, His, Leu, or Lys and examined single-channel function. Every Arg-347 mutation examined, except R347K, had a destabilizing effect on the pore, causing the channel to flutter between two conductance states. Chloride flow through the larger conductance state was similar to that of wild-type CFTR, suggesting that the residue at position 347 does not interact directly with permeating anions. We hypothesized that Arg-347 stabilizes the channel through an electrostatic interaction with an anionic residue in another transmembrane domain. To test this, we mutated anionic residues (Asp-924, Asp-993, and Glu-1104) to Arg in the context of either R347E or R347D mutations. Interestingly, the D924R mutation complemented R347D, yielding a channel that behaved like wild-type CFTR. These data suggest that Arg-347 plays an important structural role in CFTR, at least in part by forming a salt bridge with Asp-924; cystic fibrosis-associated mutations disrupt this interaction.  (+info)

Adequate representations of protein evolution should consider how the acceptance of mutations depends on the sequence context in which they arise. However, epistatic interactions among sites in a protein result in hererogeneities in the substitution rate, both temporal and spatial, that are beyond the capabilities of current models. Here we use parallels between amino acid substitutions and chemical reaction kinetics to develop an improved theory of protein evolution. We constructed a mechanistic framework for modelling amino acid substitution rates that uses the formalisms of statistical mechanics, with principles of population genetics underlying the analysis. Theoretical analyses and computer simulations of proteins under purifying selection for thermodynamic stability show that substitution rates and the stabilization of resident amino acids (the evolutionary Stokes shift) can be predicted from biophysics and the effect of sequence entropy alone. Furthermore, we demonstrate that ...
A key element in evaluating the quality of a pairwise sequence alignment is the "substitution matrix", which assigns a score for aligning any possible pair of residues. The theory of amino acid substitution matrices is described in [1], and applied to DNA sequence comparison in [2]. In general, different substitution matrices are tailored to detecting similarities among sequences that are diverged by differing degrees [1-3]. A single matrix may nevertheless be reasonably efficient over a relatively broad range of evolutionary change [1-3]. Experimentation has shown that the BLOSUM-62 matrix [4] is among the best for detecting most weak protein similarities. For particularly long and weak alignments, the BLOSUM-45 matrix may prove superior. A detailed statistical theory for gapped alignments has not been developed, and the best gap costs to use with a given substitution matrix are determined empirically. Short alignments need to be relatively strong (i.e. have a higher percentage of matching ...
Identification of specificity determining residues in enzymes using environment specific substitution tables - Quantitative Biology > Quantitative Methods. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
In this project, we develop a general framework that applies 3D convolutional neural network (3DCNN) technology to structure-based protein analysis. The framework automatically extracts task-specific features from the raw atom distribution, driven by supervised labels. As a pilot study, we use our network to analyze local protein microenvironments surrounding the 20 amino acids, and predict the amino acids most compatible with environments within a protein structure. To further validate the power of our method, we construct two amino acid substitution matrices from the prediction statistics and use them to predict effects of mutations in T4 lysozyme structures. ...
1C5I: Hydrogen bonding and catalysis: a novel explanation for how a single amino acid substitution can change the pH optimum of a glycosidase.
Single Amino Acid Mutation related change of Binding Energy (SAAMBE) method addresses the demand for computational tools of predicting the effect of single amino acid substitution on the binding free energy of protein complexes. It is based on the fast (,, 1 minute) modified MM-PBSA protocol that is successfully tested and optimized for more than thousand experimental data points. If the usage of the server results in scientific publication, please, cite the following papers: References SAAMBE is running on Clemson Universitys Palmetto Supercomputer Cluster. If you experience problems, they may be due to Palmetto Cluster being not functional or under maintenance. Contact us at [email protected] ...
Substitution Mutations: In substitution mutations, a nitrogenous base of a triplet codon of DNA is replaced by another nitrogen base or some derivative of the nitrogen base, changing the codon. The altered codon codes for a different amino acid substitution.The substitution mutations are of two types: 1.Transitions: It is the replacement of one purine in a polynucleotide chain by another purine(A by G or G by A) or one pyrimidine by another pyrimidine(T by C or C by T) 2.Transversions:A base pair substitution involving the substitution of a purine by pyrimidine or pyrimidine by a purine is called transversion. ...
Structure-function studies of potassium channels have shown that many pore loop substitutions result in a loss of functional channel expression. Some point mutations in the pore loop disrupt subunit tetramerization (Heginbotham et al., 1997), whereas in other cases channels are delivered to the cell surface, as determined by voltage-dependent gating charge movement, but potassium ion conduction through the pore is eliminated (Perozo et al., 1993). Glutamate receptor channels appear to tolerate a larger repertoire of substitutions, possibly owing to their larger pore dimensions. Estimates of pore size at the selectivity filter based on permeation of organic cations suggest a diameter of ∼5.5 Å for NMDA receptors (Villarroel et al., 1995), 7.5-7.6 Å for both Q and R forms of kainate receptors and ∼7.8 Å for AMPA receptors (Burnashev et al., 1996). In contrast, potassium channels exhibit a narrower pore diameter of ∼3 Å (Hille, 2001). With some notable exceptions, single amino acid ...
These are internal identifiers that are unique to a mutation on a particular transcript and are displayed in the URL of the mutation pages. Therefore, several of these internal ids could be associated with a single genomic COSV id where the mutation has been mapped to all overlapping genes and transcripts. Similarly, since every COSM id is mapped to one COSV id (where genomic coordinates are known), each COSM id can also be associated with several alternative (internal) identifiers. These ids are expected to change between assemblies (GRCh37 and GRCh38) and between the releases ...
The sessile nature of plants forces them to cope directly with environmental stresses, which include insect herbivory, pathogen attack, UV light radiation, and drought. Secondary metabolites are believed to be an important mechanism that allows plants to respond to these environmental challenges. There are more than 100,000 known plant secondary metabolites, which probably represent less than 10% of the actual total in nature (Wink, 1988). A large fraction of this diversity is derived from differential modification of common backbone structures, which requires the evolution of numerous enzymes with different product specificities. There are several mechanisms by which this can occur. First, as is the case with terpene synthases, a single protein can produce numerous products from a single substrate (Steele et al., 1998). A few amino acid substitutions can alter the ratio of products generated by a terpene synthase (Back and Chappell, 1996). The second mechanism is the use of gene duplication. In ...
These findings suggest that a specific substitution in a 3S-based immunogen might allow the generation of specific antibodies, providing a foundation for a rational vaccine that combine a capacity to neutralize HIV-1 and to protect CD4(+) T cells.
ants in an amino-acid sequence can bedetermined if the In addition to identifying important genetic variants substitution is in an annotated active or binding site, for research prioritization, genotyping efforts could be affects interaction with ligands present in the crystallo- reduced by eliminating amino-acid substitutions that graphic structure, leadsto hydrophobicity or electrostatic have been deemed neutral by algorithms such as charge change in a buriedsite, destroys a disulfide bond, PolyPhen. In some cases, some genes could be removed affects the proteins solubility, inserts proline in an from further consideration if all of the variant alleles α-helix,or is incompatiblewith the profile of amino-acid were deemed to be non-functional. Because prediction substitutions observed at this site in the set of homolo- algorithms provide numerical data, it is feasible to fur- gous proteins. Mapping the amino-acid substitution tothe ther subdivide the variant alleles of a gene into those ...
1LYF: Dissection of helix capping in T4 lysozyme by structural and thermodynamic analysis of six amino acid substitutions at Thr 59.
Dalla Chiesa, Marta, Martensen, Pia, Simmons, Cameron, Porakishvili, Nino, Justesen, Just, Dougan, Gordon, Roitt, Ivan M., Delves, Peter J. and Lund, Torben (2001) Refocusing of B-cell responses following a single amino acid substitution in an antigen. Immunology, 103 (2). pp. 172-178. ISSN 0019-2805 ...
Lindner, B. D., Engelhart, J. U., Tverskoy, O., Appleton, A. L., Rominger, F., Peters, A., Himmel, H.-J. and Bunz, U. H. F. (2011), Stable Hexacenes through Nitrogen Substitution. Angew. Chem. Int. Ed., 50: 8588-8591. doi: 10.1002/anie.201103676 ...
Computational prediction of protein stability change due to single-site amino acid substitutions is of interest in protein design and analysis. We consider the following four ways to improve the performance of the currently available predictors: (1) We include additional sequence- and structure-based features, namely, the amino acid substitution likelihoods, the equilibrium fluctuations of the alpha- and beta-carbon atoms, and the packing density. (2) By implementing different machine learning integration approaches, we combine information from different features or representations. (3) We compare classification vs. regression methods to predict the sign vs. the output of stability change. (4) We allow a reject option for doubtful cases where the risk of misclassification is high. We investigate three different approaches: early, intermediate and late integration, which respectively combine features, kernels over feature subsets, and decisions. We perform simulations on two data sets: (1) S1615 is used
Classifying and predicting amino acid substitutions are important in pharmaceutical and pathological research. We proposed a novel feature set from amino acids physicochemical properties, evolutionary profile of proteins, and protein sequence information. Large scale size of human disease-associated data were collected and processed, together with the unbiased experimental amino acid substitutions. Machine learning methods of decision tree, support vector machine, Gaussian mixture model, and random forests were used to classify neutral and deleterious substitutions, and the comparison of classification accuracy with published results showed that our feature set is superior to the existing ones.; We designed a simulated annealing bump hunting method to automatically extract interpretable rules for amino acid substitutions. Rules are consistent with current biological knowledge or provide new insights for understanding substitutions.; We also designed a Multiple Selection and Rule Voting (MS-RV) ...
BioAssay record AID 198913 submitted by ChEMBL: Inhibition of HIV-1 Mutant HIV-1 RT enzymes containing the single amino acid substitution V106A.
Accumulation of somatic mutations is critical for the transition of a normal cell to become cancerous. Mutations cause amino acid substitutions that change properties of proteins. However, it has not been studied as to what extent the composition and accordingly chemical properties of the cell proteome is altered as a result of the increased mutation load in cancer. Here, we analyzed data on amino acid substitutions caused by mutations in about 2000 protein coding genes from the Cancer Cell Line Encyclopedia that contains information on nucleotide and amino acid alterations in 782 cancer cell lines, and validated the analysis with information on amino acid substitutions for the same set of proteins in the Catalogue of Somatic Mutations in Cancer (COSMIC; v78) in circa 18,000 tumor samples. We found that nonsynonymous single nucleotide substitutions in the analyzed proteome subset ultimately result in a net gain of cysteine, histidine, and tryptophan at the expense of a net loss of arginine. The
Methods: In this study, E6 and E7 gene sequences were obtained from 12 samples of Indonesian isolates, which were compared with HPV16R (prototype) and 6 standard isolates in the category of European (E), Asian (As), Asian-American (AA), African-1 (Af-1), African-2 (Af-2), and North American (NA) branch from Genbank. Bioedit v.7.0.0 was used to analyze the composition and substitution of single amino acids. Phylogenetic analysis of E6 and E7 genes and proteins was performed using Clustal X (1.81) and NJPLOT softwares. Effects of single amino acid substitutions on protein function of E6 and E7 were analysed by SNAP. ...
We have previously demonstrated that substitution of Asn for Ser at position 17 of RasH yields a dominant inhibitory protein whose expression in cells interferes with endogenous Ras function (L. A. Feig, and G. M. Cooper, Mol. Cell. Biol. 8:3235-3243, 1988). Subsequent structural studies have shown that the hydroxyl group of Ser-17 contributes to the binding of Mg2+ associated with bound nucleotide. In this report, we show that more subtle amino acid substitutions at this site that would be expected to interfere with complexing Mg2+, such as Cys or Ala, also generated dominant inhibitory mutants. In contrast, a Thr substitution that conserves a reactive hydroxyl group maintained normal Ras function. These results argue that the defect responsible for the inhibitory activity is improper coordination of Mg2+. Preferential affinity for GDP, observed in the original Asn-17 mutant, was found exclusively in inhibitory mutants. However, this binding specificity did not completely block the mutant ...
Study shows that seasonal flu escapes immunity with single amino acid substitutions. Scientists have identified a potential way to improve future flu vaccines after discovering that seasonal flu typically escapes immunity from vaccines with as little as a single amino acid substitution. Additionally, they found these single amino acid changes occur at only seven places on its surface - not the 130 places previously believed. The research was published today, 21 November, in the journal Science.. "This work is a major step forward in our understanding of the evolution of flu viruses, and could possibly enable us to predict that evolution. If we can do that, then we can make flu vaccines that would be even more effective than the current vaccine," said Professor Derek Smith from the University of Cambridge, one of the two leaders of the research, together with Professor Ron Fouchier from Erasmus Medical Center in The Netherlands.. The flu vaccine works by exposing the body to parts of inactivated ...
Dear Colleagues, I am seeking pdb files to use as paired examples of the effects of a single amino acid substitution on protein structure/function. Ideally I would like to have some examples of substitutions that alter function, and some that have little or no evident functional effect. If both types of substitutions are available for the same protein, so much the better. A good example is normal and sickle cell hemoglobin, but I would like to have somewhere between four and ten different protein examples. I need some that affect binding or enzymatic activity and are located in the binding or active site. Thanks in advance for suggestions on this topic. Frieda Frieda Reichsman, PhD Molecules in Motion Interactive Molecular Structures www.moleculesinmotion.com MyDNA Project www.bio.umass.edu/biochem/mydna ...
Genes for lanosterol 14-demethylase, cytochrome P450(14DM), and a mutated inactive cytochrome P450SG1 were cloned from S. cerevisiae strains D587 and SG1, respectively. A single nucleotide change resulting in substitution of Asp for Gly-310 of cytochrome P450(14DM) was found to have occurred in cyto …
p.Pro1933Leu (CCA,CTA): c.5798 C,T in exon 41 of the MYH11 gene (#NM_022844.2). A variant of unknown significance has been identified in an alternate transcript of the MYH11 gene. The P1933L variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The P1933L variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The P1933L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is not conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Furthermore, missense mutations in this transcript have not been reported in association with TAAD. Therefore, based ...
Ns done by the Polyphen-2 software used by the Exome Variant Server (EVS) database to predict the effect of amino acid substitution on 115103-85-0 manufacturer
http://​genetics.bwh.harvard.edu/​pph2,PolyPhen-2]] is a tool for predicting the effect of an amino acid substitution on protein structure and function, based on comparative genomics and experimentally determined protein structures. It is available as a web service, and can also be downloaded as a standalone application ...
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The PPARγ2 Pro12Ala variant is protective against progression of nephropathy in people with type 2 diabetes. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
The R779C variant in the IFIH1 gene has been reported previously in two unrelated individuals with Aicardi-Goutières syndrome, one which the R779C variant was shown to occur de novo (Rice et al., 2014; Marguet et al., 2016). The R779C variant is not observed in large population cohorts (Lek et al., 2016). The R779C variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Functional studies show the R779C variant demonstrates a gain of function mechanism, enhancing the interferon signaling pathway activation, stability of filament formation, and dsRNA binding activity (Rice et al., 2014). We interpret R779C as a pathogenic variant. (less) ...
It contains the values of a, b, c and E damping parameters for amino acid substitution scores. Generally, if a residue is completely buried ( Area=0), its substitution scores will be used without changes. If it is completely exposed, its substitution scores will be multiplied by the minimal possible value of a. Between these cases the substitution scores are modulated by a smooth ("arctangent") function with a saddle point at Area=c, where the slope will be -b. The fourth parameter is reserved for development ...
TY - JOUR. T1 - Enhancement of thermoelectric properties by Se substitution in layered bismuth-chalcogenide LaOBiS2-xSex. AU - Mizuguchi, Yoshikazu. AU - Omachi, Atsushi. AU - Goto, Yosuke. AU - Kamihara, Yoichi. AU - Matoba, Masanori. AU - Hiroi, Takafumi. AU - Kajitani, Joe. AU - Miura, Osuke. PY - 2014/1/1. Y1 - 2014/1/1. N2 - We have investigated the thermoelectric properties of the novel layered bismuth chalcogenides LaOBiS2-xSex. The partial substitution of S by Se produced the enhancement of electrical conductivity (metallic characteristics) in LaOBiS2-xSex. The power factor largely increased with increasing Se concentration. The highest power factor was 4.5 μW/cmK2 at around 470 °C for LaOBiS1.2Se0.8. The obtained dimensionless figure-of-merit (ZT) was 0.17 at around 470 °C in LaOBiS1.2Se0.8.. AB - We have investigated the thermoelectric properties of the novel layered bismuth chalcogenides LaOBiS2-xSex. The partial substitution of S by Se produced the enhancement of electrical ...
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A crucial prerequisite for plant growth and survival is the maintenance of potassium uptake, especially when high sodium surrounds the root zone. The Arabidopsis HIGH-AFFINITY K+ TRANSPORTER1 (HKT1), and its homologs in other salt-sensitive dicots, contributes to salinity tolerance by removing Na+ from the transpiration stream. However, TsHKT1;2, one of three HKT1 copies in Thellungiella salsuginea, a halophytic Arabidopsis relative, acts as a K+ transporter in the presence of Na+ in yeast (Saccharomyces cerevisiae). Amino-acid sequence comparisons indicated differences between TsHKT1;2 and most other published HKT1 sequences with respect to an Asp residue (D207) in the second pore-loop domain. Two additional T. salsuginea and most other HKT1 sequences contain Asn (n) in this position. Wild-type TsHKT1;2 and altered AtHKT1 (AtHKT1N-D) complemented K+-uptake deficiency of yeast cells. Mutant hkt1-1 plants complemented with both AtHKT1N-D and TsHKT1;2 showed higher tolerance to salt stress than ...
Where did the nylon-eating ability come from? Carboxylesterases are enzymes with broad substrate specificities; they can carry out a variety of reactions. Their binding pocket is large and can accommodate a lot of different substrates. They are "promiscuous" enzymes, in other words. Furthermore, the carboxylesterase reaction hydrolyzes a chemical bond similar to the one hydrolyzed by nylonase.. […]. From Kato et al. (1991):. "Our studies demonstrated that among the 47 amino acids altered between the EII and EII proteins, a single amino acid substitution at position 181 was essential for the activity of 6-aminohexanoate-dimer hydrolase [nylonase] and substitution at position 266 enhanced the effect.". So. This is not the story of a highly improbable frame-shift producing a new functional enzyme. This is the story of a pre-existing enzyme with a low level of promiscuous nylonase activity, which improved its activity toward nylon by first one, then another selectable mutation. In other words ...
English) A Simple Mechanism Based on Amino Acid Substitutions is not a Critical Determinant of High Mortality of Japanese Encephalitis Virus Infection in Mice ...
The Y155H amino acid substitution in the neuraminidase gene (NA) has previously been associated with highly reduced inhibition by neuraminidase inhibitors in the seasonal H1N1 influenza A virus which circulated in humans before the 2009 pandemic. During the 2012/13 epidemic season in Spain, two A(H1N1)pdm09 viruses bearing the specific Y155H substitution in the NA were detected and isolated from two patients diagnosed with severe respiratory syndrome and pneumonia requiring admission to the intensive care unit. Contrary to what was observed in the seasonal A(H1N1) viruses, neither of the Y155H A(H1N1)pdm09 viruses described here showed a phenotype of reduced inhibition by NAIs as determined by the neuraminidase enzyme inhibition assay (MUNANA). High-throughput sequencing of the NA of both Y155H viruses showed that they were composed to >99% of H155 variants. We believe that this report can contribute to a better understanding of the biological significance of amino acid substitutions in the
Five point mutations within the amyloid beta-protein (Abeta) sequence of the APP gene are associated with hereditary diseases which are similar or identical to Alzheimers disease and encode: the A21G (Flemish), E22G (Arctic), E22K (Italian), E22Q (Dutch) and the D23N (Iowa) amino acid substitutions. Although a substantial body of data exists on the effects of these mutations on Abeta production, whether or not intra-Abeta mutations alter degradation and how this relates to their aggregation state remain unclear. Here we report that the E22G, E22Q and the D23N substitutions significantly increase fibril nucleation and extension, whereas the E22K substitution exhibits only an increased rate of extension and the A21G substitution actually causes a decrease in the extension rate. These substantial differences in aggregation together with our observation that aggregated wild type Abeta(1-40) was much less well degraded than monomeric wild type Abeta(1-40), prompted us to assess whether or not ...
It is currently unclear whether the amino acid substitutions that occur during protein evolution are primarily driven by adaptation, or reflect the random accumulation of neutral changes. When estimated from genomic data, the proportion of adaptive amino acid substitutions, called , was found to vary greatly across species, from nearly zero in humans to above 0.5 in Drosophila. These variations have been interpreted as reflecting differences in effective population size, adaptation being supposedly more efficient in large populations. Here, we investigate the influence of effective popu-lation size and other biological parameters on the rate of adaptive evolution by simulating the evolution of a coding sequence under Fishers geometric formalism. We explicitly model recurrent environmental changes and the subsequent adaptive walks, followed by periods of stasis during which purifying selection dominates. We show that, under a variety of conditions, the effective population size has only a ...
Abstract: Proteomic studies of some human tissues and organs (skeletal muscles, myometrium, motor zone of the brain, prostate), and also cultivated myoblasts revealed 41 of 300 identified proteins, in which the present of certain variants of amino acids (conflicts) was recognized at several positions. Among the 93 registered amino acids conflicts, seven cases represented the results of the protein polymorphisms caused by corresponding substitution of individual amino acid. Moreover, among prostate proteins the proteomic analysis revealed two isoforms of prostate-specific antigen, formed due to alternative splicing. Thus, our results have shown, that proteomic technologies allow to specify effectively the features of primary structures and to characterize various kinds of polymorphism in many human proteins ...
Mutations leading to hemophilia A by substitution of amino acids in coagulation factor VIII may provide important clues to the structure and function of this large and enigmatic protein. To efficiently find missense mutations, hemophiliacs with mild
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Lower your blood pressure with one single amino acid If you have stubborn hypertension, you might be interested in a simple and inexpensive treatment. Its a single amino acid. As you may know, amino acids are the building blocks of proteins. But many amino acids serve as raw materials for key molecules. For example, tryptophan and phenylalanine serve as raw materials for neurotransmitters. A deficiency in either of these can lead to mood disorders.
Just a few viruses fell into subgroup 3B and group 6 (Fig. 4, Fig. S4). Some isolates from North America, Europe and Asia belonged to groups 5 and 6, which have signature AA substitutions D53N, Y94H, I230V and E280A in HA1, with group 6 isolates carrying an additional AA substitution S199A. Viruses with low HI titres to post-infection ferret antisera raised against cell-propagated A/Victoria/361/2011 viruses were scattered throughout the HA tree and did not form monophyletic groups or share common AA substitutions. Genetic analysis OSI 906 of the HA sequences of several egg-propagated A/Victoria/361/2011-like. viruses were compared in order to see if low HI titres might be associated with amino acid substitutions linked to adaptation to growth in eggs. A number of such substitutions were noted in the HA of the initial egg-propagated A/Victoria/361/2011 wild-type virus, including a H156R substitution. A. subsequent R156Q change was acquired in the high growth reassortants IVR-165 and X221, ...
The S14L variant has been reported in individuals with autism and seizures, although the phenotype was variable with reduced penetrance and did not uniformly include seizures (Feng et al., 2006; Gauthier et al., 2011; Yangngam et al., 2014). This variant is in the shorter transcript of NRXN1 (NM_138735.2), and alters a residue that is predicted to be in the signal peptide of the beta-neurexin protein (Zweier et al., 2009; Gauthier et al., 2011). Although the S14L was not observed in 1,201 controls studied separately (Feng et al., 2006; Gauthier et al., 2011; Kim et al., 2008), it was observed in 1/200 controls in an additional publication (Camacho-Garcia et al., 2012). This variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size, and/or other properties. However, this substitution occurs at a position that is not conserved, and functional studies have shown no abnormalities in beta-neurexin ...
In article ,90luod$kkb$1 at mercury.hgmp.mrc.ac.uk,, James McInerney ,james.o.mcinerney at may.ie, wrote: ,I have a question about selection on genes in HIV (but probably anywhere). ,In some HIV genes there is often a great excess of replacement substitutions ,over silent substitutions. In the past we would say that this meant that ,there was a positive selection event involved. However, if there is no ,selective difference between substitutions that occur in synonymous and ,non-synonymous sites then we would see about three times as many ,substitutions that are replacement than silent. I believe such studies generally take this into account. They reckon up how many sites *could* have a synonymous or nonsynonymous (S and N from here on) substitution, and weight by how many such substitutions could occur (a fourfold degenerate site contributes more possible S substitutions than a twofold ones). So the actual statistic is the ratio of S mutations per S site and N mutations per N site. This is ...
Different base substitutions or amino acid substitutions can have different scores. The substitution matrix of amino acids is ... Substitution matrix[edit]. Each base substitution or amino acid substitution is assigned a score. In general, matches are ... Determine the substitution matrix and the gap penalty scheme. A substitution matrix assigns each pair of bases or amino acids a ... Substitution matrix: s. (. a. i. ,. b. j. ). =. {. +. 3. ,. a. i. =. b. j. −. 3. ,. a. i. ≠. b. j. {\displaystyle s(a_{i},b_{j ...
The absence of substitutions, or the presence of only very conservative substitutions (that is, the substitution of amino acids ... color is often used to indicate amino acid properties to aid in judging the conservation of a given amino acid substitution. ... In typical usage, protein alignments use a substitution matrix to assign scores to amino-acid matches or mismatches, and a gap ... Ng PC; Henikoff S (May 2001). "Predicting deleterious amino acid substitutions". Genome Res. 11 (5): 863-74. doi:10.1101/gr. ...
The amino acid substitutions impaired corin activity. An insertion variant in exon 1 alters the cytoplasmic tail. This variant ... Human corin, a polypeptide of 1042 amino acids, consists of an N-terminal cytoplasmic domain, a transmembrane domain and an ...
Two major forces drive the amino-acid substitution rates away from uniformity: substitutions occur with the different ... However, these amino acids can be categorised into groups with similar physicochemical properties. Substituting an amino acid ... Substitution matrices for amino acids are more complicated and implicitly take into account everything that might affect the ... Then, they calculated a log-odds score for each of the 210 possible substitution pairs of the 20 standard amino acids. All ...
"Amino Acid Substitution Matrices from Protein Blocks". PNAS. 89 (22): 10915-10919. doi:10.1073/pnas.89.22.10915. PMC 50453 . ... In 1992, Steven Henikoff, together with his wife Jorja Henikoff, introduced the BLOSUM substitution matrices. The BLOSUM ...
Mitraki A, King J (Jul 1992). "Amino acid substitutions influencing intracellular protein folding pathways". FEBS Letters. 307 ... P22TSP is a homotrimeric structural protein consisting of 666 amino acids. It is noncovalently bound to the neck of the viral ... Two aspartic acids and one glutamic acid in the active site have been strongly linked to enzymatic activity. Different ...
Betts, M.J.; R.B. Russell (2003). "Hydrophobic amino acids". Amino Acid Properties and Consequences of Substitutions, In: ... Non-Polar Amino Acids". Archived from the original on 2012-09-05. Retrieved 2012-09-16. "Virtual Chembook--Amino Acid Structure ... so it must be biosynthesized from its constituent amino acids, cysteine, glycine and glutamic acid. Glutamic acid and glycine ... interactions in micelles to a greater degree than the side chain in the non-polar amino acid glycine and the polar amino acid ...
Similarities between amino acids or nucleotides are quantified in these substitution matrices. The substitution score ( S {\ ... mutating into amino acid b {\displaystyle b} [2]. In a large set of sequence alignments, counting the number of amino acids as ... "Discriminative Modelling of Context-specific Amino Acid Substitution Properties" BIOINFORMATICS 28.24 (2012): 3240-247. Oxford ... In predicting substitution probabilities using only the amino acid's local sequence context, you gain the advantage of not ...
"Discriminative modelling of context-specific amino acid substitution probabilities". Bioinformatics. 28 (24): 3240-7. doi: ... September 1997). "Gapped BLAST and PSI-BLAST: a new generation of protein database search programs". Nucleic Acids Research. 25 ... 1998). Biological sequence analysis: probabilistic models of proteins and nucleic acids. Cambridge, UK: Cambridge University ... Nucleic Acids Research. 34 (17): e112. doi:10.1093/nar/gkl480. PMC 1635247 . PMID 16971460. Girdea, M; Noe, L; Kucherov, G ( ...
"Predicting the functional consequences of cancer-associated amino acid substitutions". Bioinformatics. 29 (12): 1504-10. doi: ... His research has been published in leading peer reviewed scientific journals including Nature, Science, Cell, Nucleic Acids ... 2005). "InterPro, progress and status in 2005". Nucleic Acids Research. 33 (Database issue): D201-5. doi:10.1093/nar/gki106. ... SCOP sequence searches, alignments and genome assignments". Nucleic Acids Research. 30 (1): 268-272. doi:10.1093/nar/30.1.268. ...
Takakubo F, Cartwright P, Hoogenraad N, Thorburn DR, Collins F, Lithgow T, Dahl HH (Oct 1995). "An amino acid substitution in ... Structural implications of novel amino acid substitutions in E1 protein". Molecular Genetics and Metabolism. 104 (4): 507-16. ... The preliminary peptide encoded by this gene was 29 amino acids at the very start of the sequence that correspond to a typical ... The remaining 361 amino acids, starting at the N terminus with phenylalanine, represent the mature mitochondrial E1 alpha ...
"Selective amino acid substitution reduces cytotoxicity of the antimicrobial peptide mastoparan". Biochimica et Biophysica Acta ...
"Codon-substitution models for heterogeneous selection pressure at amino acid sites". Genetics. 155: 431-449. CS1 maint: ... on different amino acids in the protein and can be used to test for positive selection affecting only a few amino acid sites. ... And the branch-site models attempt to detect positive selection that affects only a few amino acid sites along pre-specific ... Yang Z, Kumar S, Nei M. (1995). "A new method of inference of ancestral nucleotide and amino acid sequences". Genetics. 141: ...
... amino acid-specific SLs can be used. The goal of spin labeling is somewhat similar to that of isotopic substitution in NMR ... For example, stearic acid labelled with nitroxyl spin label moiety at various carbons (5,7,9,12,13,14 and 16th) with respect to ... Spin labelled fatty acids have been extensively used to understand dynamic organization of lipids in bio-membranes and membrane ... This technique is useful for tracking the chemical environment around an atom when full substitution with an NMR-active isotope ...
Gu X, Li W (1992). "Higher rates of amino acid substitution in rodents than in man". Molecular Phylogenetics and Evolution. 1 ( ... for an amino acid sequence (there are 20 "standard" amino acids that make up proteins), one would find there are 209 parameters ... a codon is three bases and codes for one amino acid in a protein). There are 4 3 = 64 {\displaystyle 4^{3}=64} codons, but the ... These substitution models differ in terms of the parameters used to describe the rates at which one nucleotide replaces another ...
"Greater efficiency of photosynthetic carbon fixation due to single amino-acid substitution". Nature Communications. 4 (2): 1518 ... The sequence length is about 966 amino acids. See figure 1 for a PyMOL generated structure of the enzyme's single subunit from ... It includes a conserved aspartic acid (D564) and a glutamic acid (E566) residue that non-covalently bind a divalent metal ... such as for example amino acids. PEP carboxylase is mainly subject to two levels of regulation: phosphorylation and allostery. ...
... such as clavulanic acid. Single amino acid substitutions at positions 104, 164, 238, and 240 produce the ESBL phenotype, but ... Amino acid substitutions in OXA enzymes can also give the ESBL phenotype. While most ESBLs have been found in E. coli, K. ... Ten variants, KPC-2 through KPC-11 are known, and they are distinguished by one or two amino acid substitutions (KPC-1 was re- ... The amino acid substitutions responsible for the extended-spectrum beta lactamase (ESBL) phenotype cluster around the active ...
Phenylalanine, a common amino acid. Biphenyl, consisting of two phenyl groups. The two rings tend not to be coplanar. ... are associated with electrophilic aromatic substitution reactions and the products follow the arene substitution pattern. So, a ... Most common among natural products is the amino acid phenylalanine, which contains a phenyl group. A major product of the ... Higher degrees of substitution, of which the pentafluorophenyl group is an example, exist, and are named according to IUPAC ...
"Hydrophobic amino acids". Amino Acid Properties and Consequences of Substitutions, In: Bioinformatics for Geneticists. Wiley. ... and glutamic acid. While glutamic acid is usually sufficient because amino acid nitrogen is recycled through glutamate as an ... Cysteine (symbol Cys or C;[3] /ˈsɪstiiːn/)[4] is a semiessential[5] proteinogenic amino acid with the formula HO2CCH(NH2)CH2SH ... interactions in micelles to a greater degree than the side chain in the nonpolar amino acid glycine and the polar amino acid ...
"Hydrophobic amino acids". Amino Acid Properties and Consequences of Substitutions, In: Bioinformatics for Geneticists. Wiley. ... so it must be biosynthesized from its constituent amino acids, cysteine, glycine and glutamic acid. Glutamic acid and glycine ... Cysteine (symbol Cys or C;[3] /ˈsɪstiiːn/)[4] is a semi-essential[5] proteinogenic amino acid with the formula HO2CCH(NH2)CH2SH ... interactions in micelles to a greater degree than the side chain in the non-polar amino acid glycine and the polar amino acid ...
Character state changes can be phenotypic changes, nucleotide substitutions, or amino acid substitutions. These small changes ...
The first haplotype is seven amino acids in strong linkage disequilibrium. This haplotype is global and seems to be moving ... They specifically wanted to know how synonymous substitutions affected the evolutionary landscape of a protein. To do this, ... A synonymous protein has the same amino acid sequence but different nucleotide sequences. Thus, a synonymous protein has the ...
Garel MC, Lemarchandel V, Calvin MC, Arous N, Craescu CT, Prehu MO, Rosa J, Rosa R (April 1993). "Amino acid residues involved ... Functional consequences of substitutions of His10, His187 and Arg89". Eur. J. Biochem. 213 (1): 493-500. doi:10.1111/j.1432- ...
The primary structure is depicted in Table 1. Substitution of the 16th amino acid, asparagine (N), into an aspartic acid (D) is ... It has two homologous amino acid substitutions (S17T and S19T) and one non-homologous substitution (V13S). This makes it 94% ... Cangitoxin is a 4958 Da peptide containing 48 amino acid residues. ... a replacement of the 14th amino acid, arginine (R), into histidine (H). Cangitoxin is to varying degrees homologous to the ...
The single nucleotide substitution between G--> A results in an amino acid change from valine to methionine at codon 158. The A ...
... fatty acids, and amino acids in most vertebrates, including humans. Ketone bodies are elevated in the blood (ketosis) after ... depending on alkene substitution pattern.[14] ... Acid/base properties of ketonesEdit. Ketones are far more ... Acids as weak as pyridinium cation (as found in pyridinium tosylate) with a pKa of 5.2 are able to serve as catalysts in this ... Ketonium ions (i.e., protonated ketones) are strong acids, with pKa values estimated to be somewhere between -5 and -7.[6][7] ...
Amino acid substitution matrices from protein blocks. S Henikoff and J G Henikoff ...
Functional Consequences of Amino Acid Substitutions to GerVB, a Component of the Bacillus megaterium Spore Germinant Receptor ... Lineage-Specific Amino Acid Substitutions in Region 2 of the RNA Polymerase σ Subunit Affect the Temperature of Promoter ... Amino Acid Substitutions in Transmembrane Domains 9 and 10 of GerVB That Affect the Germination Properties of Bacillus ... Switching Protein-DNA Recognition Specificity by Single-Amino-Acid Substitutions in the P1 par Family of Plasmid Partition ...
... amino acids or codons that encode the amino acids. Codon models incorporate nucleotide and amino acid information, and allow ... The pattern of amino acid substitutions specific to a given alignment can be used to compare and contrast the evolutionary ... The addition of amino acid properties can lead to more powerful and accurate methods for studying natural selection and the ... Indeed, amino acid models have consistently demonstrated that different residues are exchanged more or less frequently, ...
... sequences typically measure similarity by using a substitution matrix with scores for all possible exchanges of one amino acid ... Amino acid substitution matrices from protein blocks Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10915-9. doi: 10.1073/pnas. ... sequences typically measure similarity by using a substitution matrix with scores for all possible exchanges of one amino acid ... Using a different approach, we have derived substitution matrices from about 2000 blocks of aligned sequence segments ...
... decreases linearly with the increase in physico-chemical differences between amino acid pairs involved in a... ... The frequency of amino acid substitutions, relative to the frequency expected by chance, ... Amino acid substitution Physico-chemical difference Conservative Low-constraint Protein evolution This is a preview of ... The frequency of amino acid substitutions, relative to the frequency expected by chance, decreases linearly with the increase ...
a) Giraffe FGFRL1 contains seven amino acid substitutions that are unique at fixed sites in other mammals and/or are predicted ... Figure 3 : Giraffe genes and pathways exhibiting extraordinary divergence and patterns of amino acid substitutions.. From: ... The giraffe and okapi MDC1 gene exhibits a 264 amino acid deletion that removes part of the SDT region that harbours two ... The unique substitution in giraffe, G234Q, immediately adjacent to the Gpi anchor site may alter the anchor site or the rate of ...
... tools primarily focus on studying the deleterious effects of single amino acid substitutions through examining amino acid ... and multiple amino acid substitutions. This alignment-based score measures the change in sequence similarity of a query ... score as a new metric to predict the damaging effects of variations not limited to single amino acid substitutions but also in- ... approach to predict the functional effects of protein sequence variations including single or multiple amino acid substitutions ...
PolyPhen-2 and SIFT had significantly lower accuracies in predicting the effects of amino acid substitutions outside CFDs than ... There are more than 500 amino acid substitutions in each human genome, and bioinformatics tools irreplaceably contribute to ... Feature-Based Classification of Amino Acid Substitutions outside Conserved Functional Protein Domains. Branislava Gemovic, ... are more suitable for the classification of amino acid substitutions outside CFDs than phylogeny-based tools. ...
Amino Acid Motifs · Amino Acid Sequence · Amino Acid Substitution · Catalysis · Circular Dichroism · Cloning, Molecular · ... Amino Acid Sequence · Amino Acid Substitution · Animals · Binding Sites · Cattle · Glutamine · Lactoglobulins · Lysine · Milk ... Antibiotic agent · Amino acid substitution · Amino terminal sequence · Article · Controlled study · Drug screening · Drug ... Both cyclic and d-amino acid variants showed enhanced stability in human serum compared to C1-15 and F2,5,12W. The d-amino acid ...
Preliminary review of D222G amino acid substitution in the haemagglutinin of pandemic influenza A (H1N1) 2009 viruses.. [ ...
... Halvarsson, Camilla Linköping University, Department of ... BACE1, disulphide bonds substitution, hydrophobic amino acids, protein purification, refolding time National Category Medical ...
Paland and Lynch (1) demonstrated this effect in Daphnia pulex by showing that the rates of amino acid replacement substitution ... Comment on Transitions to Asexuality Result in Excess Amino Acid Substitutions Message Subject. (Your Name) has forwarded a ... A class of moderately deleterious amino acid substitutions has a higher probability of spreading to fixation in asexual ... the ratio of amino acid replacement to silent substitution in mitochondrial genes is higher in asexual lineages than in sexual ...
A unique amino acid substitution, T126I, in human genotype C of hepatitis B virus S gene and its possible influence on ... Amino acid substitutions in the S gene of hepatitis B virus (HBV), especially in the a determinant region, have been ... The results showed that an amino acid substitution within the a determinant, T126I, was unique to genotype C, may affect the ... signals of natural selection and provide insights into the functional significance of the observed amino acid substitutions. In ...
Here we present amino acid substitution matrices constructed from the alignment of a large number of protein domain structures ... Homology search algorithms employ amino acid substitution matrices to detect similarity between proteins sequences. The ... Keywords: computational biology, protein homology, amino acid substitution matrix, protein structure ... We show that when incorporated into the homology search algorithms BLAST and PSI-blaST, the structure-based substitution ...
... tools primarily focus on studying the deleterious effects of single amino acid substitutions through examining amino acid ... and multiple amino acid substitutions. This alignment-based score measures the change in sequence similarity of a query ... score as a new metric to predict the damaging effects of variations not limited to single amino acid substitutions but also in- ... approach to predict the functional effects of protein sequence variations including single or multiple amino acid substitutions ...
Rates of amino acid substitution are higher in the D. melanogaster lineage than in D. simulans in 14 genes for which outgroup ... Molecular Evolution Between Drosophila melanogaster and D. simulans Reduced Codon Bias, Faster Rates of Amino Acid Substitution ... Molecular Evolution Between Drosophila melanogaster and D. simulans Reduced Codon Bias, Faster Rates of Amino Acid Substitution ... Molecular Evolution Between Drosophila melanogaster and D. simulans Reduced Codon Bias, Faster Rates of Amino Acid Substitution ...
... a novel explanation for how a single amino acid substitution can change the pH optimum of a glycosidase. ... HYDROGEN BONDING AND CATALYSIS: AN UNEXPECTED EXPLANATION FOR HOW A SINGLE AMINO ACID SUBSTITUTION CAN CHANGE THE PH OPTIMUM OF ...
We also tested a virus presenting a truncation of 109 amino acids at the C-terminal part of Env, a cytoplasmic tail partial ... Single Amino Acid Substitution N659D in HIV-2 Envelope Glycoprotein (Env) Impairs Viral Release and Hampers BST-2 Antagonism. ... "Single Amino Acid Substitution N659D in HIV-2 Envelope Glycoprotein (Env) Impairs Viral Release and Hampers BST-2 Antagonism." ... Dufrasne, F.E.; Lombard, C.; Goubau, P.; Ruelle, J. Single Amino Acid Substitution N659D in HIV-2 Envelope Glycoprotein (Env) ...
Evidence that the Origin of Naked Kernels During Maize Domestication Was Caused by a Single Amino Acid Substitution in tga1. ... Evidence that the Origin of Naked Kernels During Maize Domestication Was Caused by a Single Amino Acid Substitution in tga1. ... Evidence that the Origin of Naked Kernels During Maize Domestication Was Caused by a Single Amino Acid Substitution in tga1. ... Evidence that the Origin of Naked Kernels During Maize Domestication Was Caused by a Single Amino Acid Substitution in tga1 ...
A single nucleotide change resulting in substitution of Asp for Gly-310 of cytochrome P450(14DM) was found to have occurred in ... A single amino acid substitution converts cytochrome P450(14DM) to an inactive form, cytochrome P450SG1: complete primary ... A single nucleotide change resulting in substitution of Asp for Gly-310 of cytochrome P450(14DM) was found to have occurred in ...
In addition, a novel triple amino acid substitution from TAP (wild type, GSH) to IVS (triple mutant, GRH) was identified in the ... The nucleotide substitutions consisted of ATA102, GTC103 and TCA106 instead of ACA102, GCG103, and CCA106, respectively. The ... "The Triple Amino Acid Substitution TAP-IVS in the EPSPS Gene Confers High Glyphosate Resistance to the Superweed Amaranthus ... The Triple Amino Acid Substitution TAP-IVS in the EPSPS Gene Confers High Glyphosate Resistance to the Superweed Amaranthus ...
Catalytic and structural effects of amino acid substitution at histidine 30 in human manganese superoxide dismutase: insertion ... CATALYTIC AND STRUCTURAL EFFECTS OF AMINO-ACID SUBSTITUTION AT HIS 30 IN HUMAN MANGANESE SUPEROXIDE DISMUTASE: INSERTION OF VAL ... Acids Res. 2008 36: D419-D425 * [4] Alexandrov N., Shindyalov I. (2003). PDP: protein domain parser.. Bioinformatics 2003 Feb; ...
... method for Gene-Specific Substitution Profile), a method to construct amino acid substitution profiles from next-generation ... method for Gene-Specific Substitution Profile), a method to construct amino acid substitution profiles from next-generation ... To investigate the intrinsic mutation frequency and substitution bias of SHMs at the amino acid level, we analyzed functional ... To investigate the intrinsic mutation frequency and substitution bias of SHMs at the amino acid level, we analyzed functional ...
While aminoacyl-tRNA synthetases supply ribosome with amino ... A single amino acid substitution affects the substrate ... A single amino acid substitution affects the substrate specificity of the seryl-tRNA synthetase homologue A. Maršavelski, S. ... The detailed computational study aiming to address this unexpected substrate specificity toward the small aliphatic amino acids ... While aminoacyl-tRNA synthetases supply ribosome with amino acids for protein biosynthesis, this homologue transfers the ...
Introduction of a single amino acid substitution (Gln979 to Ile) into the 130- and 180-kDa proteins of tomato mosaic ... Introduction of a single amino acid substitution (Gln979 to Ile) into the 130- and 180-kDa proteins of tomato mosaic ...
  • It was found that the A281G substitution greatly affects the enzyme specificity and allows efficient activation of both polar and small aliphatic amino acids (serine, glycine and alanine), confirming predictions and conclusions based on molecular dynamics simulations. (rsc.org)
  • The valine, alanine, and glycine replacements were observed to be somewhat more destabilizing than serine, asparagine, and aspartic acid. (semanticscholar.org)
  • The reactive serine of the TGGHSL thioester binding motif of the first amino acid-activating domain of surfactin synthetase was replaced by alanine using site-directed mutagenesis. (elsevier.com)
  • The results show that l-Glu is acativated at the first domain of surfactin synthetase, and give further evidence that a serine residue is essential for substrate amino acid activation at the reaction centers of peptide synthetases. (elsevier.com)
  • By evaluating the genetic variability of HpHbR in a comprehensive geographical and taxonomic context, we show that a single substitution that replaces leucine with serine at position 210 is conserved in the most widespread form of Tbg (Tbg group 1) and not found in related taxa, which are either human serum susceptible (Tbb) or known to resist lysis via an alternative mechanism (Tbr and Tbg group 2). (unibas.ch)
  • One hypothesis suggests that the virus crossed the species barrier from birds to humans in part due to critical mutations in the HA (H1 subtype) that changed the binding preference from the avian sialic acid (α2,3) linkage to the human (α2,6) form ( 1 , 12 , 23 ). (asm.org)
  • Mutations leading to hemophilia A by substitution of amino acids in coagulation factor VIII may provide important clues to the structure and function of this large and enigmatic protein. (biomedsearch.com)
  • The hemagglutination-inhibition assay revealed an evident impact of mutations at sites 88, 156, 205, 208, 239 and 289 to the HA antigenicity, and highlighted that the amino acid substitutions located in the antigenic region B, especially the combined mutations at sites 205 and 208, were the major antigenic determinant which was also consistent with results from flow cytometry and antigenic mapping. (flu.org.cn)
  • Mutations on W74, S237, S240, I247 and L266 in the extracellular loops 1 and 2 severely impaired the inhibitory effect of BzATP, indicating that they might be the essential amino acids in the putative binding site. (elsevier.com)
  • DNA sequencing discovered two mutations at nt 353 (A to T) and nt 349 (T to A), leading to Thr to Met and Ser to Thr substitutions at aa 118 and 117 of HBsAg, respectively. (microbiologyresearch.org)
  • Results: S. pyogenes TU-296 was found to have the following mutations and amino acid substitutions: adenine 476 to cytosine in gyrA and cytosine 367 to thymine in parC, resulting in Glu-85→Ala in GyrA and Ser-79→Phe in ParC. (elsevier.com)
  • We present here a one-tube-only standardized SDM approach that generates comprehensive collections of amino acid substitution variants, including scanning- and single site-multiple mutations. (jesuscortes.info)
  • The PAM1 matrix is used as the basis for calculating other matrices by assuming that repeated mutations would follow the same pattern as those in the PAM1 matrix, and multiple substitutions can occur at the same site. (wikipedia.org)
  • The optimal MHC class I presentable peptide length is most likely generated by N-terminal trimming by ER resident ( 19 , 20 , 21 ) or cytosolic amino peptidases, as has recently been suggested for the OVA CTL epitope ( 17 , 22 ). (jimmunol.org)
  • The gene encoding the C18-defined antigen was identified as a mutated form of a mouse mitogen-activated protein kinase, ERK2, and a peptide incorporating the resulting amino acid substitution (lysine to glutamine) was efficiently recognized by C18. (pnas.org)
  • Structural modeling showed that the amino acid substitution could alter the peptide preference of the ligand-binding pocket. (cdc.gov)
  • We demonstrate that a specialist herbivore minimizes the activation of defenses by converting an elicitor into an antagonist effector and identify an amino acid substitution that recovers these induced plant defenses to a level observed with generalist herbivores. (plantphysiol.org)
  • Here, we identify an amino acid substitution in COI that is universal among hummingbirds, rare and unfixed among other birds and vertebrates, and limited to a small set of disparate clades among metazoans. (g3journal.org)
  • PolyPhen-2 and SIFT had significantly lower accuracies in predicting the effects of amino acid substitutions outside CFDs than expected, with especially low sensitivity. (hindawi.com)
  • Amino Acid Substitution" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (uchicago.edu)
  • We show that when incorporated into the homology search algorithms BLAST and PSI-blaST, the structure-based substitution matrices enhance the efficacy of detecting remote homologs. (dovepress.com)
  • Based on homology with the pore loop of potassium channels, locations at which R substitution induces susceptibility to fatty acid inhibition face away from the cytoplasm toward the M1 and M3 helices and surrounding lipids. (rupress.org)
  • The Y155H amino acid substitution in the neuraminidase gene (NA) has previously been associated with highly reduced inhibition by neuraminidase inhibitors in the seasonal H1N1 influenza A virus which circulated in humans before the 2009 pandemic. (eurosurveillance.org)
  • Nucleic Acids Res. (uchicago.edu)
  • This work will be extended and combined with new experimental data, including small and wide angle X-ray scattering and NMR, to develop and refine empirical modifications to a fixed charge nucleic acid force field. (nist.gov)
  • The presence of an R467K amino acid substitution and loss of allelic variation correlate with an azole-resistant lanosterol 14alpha demethylase in Candida albicans. (asm.org)
  • Amino acid substitutions in the S gene of hepatitis B virus (HBV), especially in the 'a' determinant region, have been suggested to affect the antigenicity of the virus and the clinical outcome of the infected patient. (nih.gov)
  • Multiple regression analyses were performed correlating overall stability with the hydrophobicity, size, and helix propensity of the replacement amino acid. (rice.edu)
  • A single amino acid substitution (R467K) that occurred in isolate 13 was identified in both alleles of ERG16. (asm.org)
  • The specific activity of CYP51(R467K) for the release of formic acid from 3β-[32- 3 H]hydroxylanost-7-en-32-ol was 70 pmol/nmol of P450/min for microsomal protein compared to 240 pmol/nmol of P450/min for microsomal fractions expressing wild-type CYP51. (asm.org)