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.Glutamate Decarboxylase: A pyridoxal-phosphate protein that catalyzes the alpha-decarboxylation of L-glutamic acid to form gamma-aminobutyric acid and carbon dioxide. The enzyme is found in bacteria and in invertebrate and vertebrate nervous systems. It is the rate-limiting enzyme in determining GAMMA-AMINOBUTYRIC ACID levels in normal nervous tissues. The brain enzyme also acts on L-cysteate, L-cysteine sulfinate, and L-aspartate. EC 4.1.1.15.Glutamates: Derivatives of GLUTAMIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the 2-aminopentanedioic acid structure.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.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.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.gamma-Aminobutyric Acid: The most common inhibitory neurotransmitter in the central nervous system.Stiff-Person Syndrome: A condition characterized by persistent spasms (SPASM) involving multiple muscles, primarily in the lower limbs and trunk. The illness tends to occur in the fourth to sixth decade of life, presenting with intermittent spasms that become continuous. Minor sensory stimuli, such as noise and light touch, precipitate severe spasms. Spasms do not occur during sleep and only rarely involve cranial muscles. Respiration may become impaired in advanced cases. (Adams et al., Principles of Neurology, 6th ed, p1492; Neurology 1998 Jul;51(1):85-93)Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Diabetes Mellitus, Type 1: A subtype of DIABETES MELLITUS that is characterized by INSULIN deficiency. It is manifested by the sudden onset of severe HYPERGLYCEMIA, rapid progression to DIABETIC KETOACIDOSIS, and DEATH unless treated with insulin. The disease may occur at any age, but is most common in childhood or adolescence.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.Chromatography, Paper: An analytical technique for resolution of a chemical mixture into its component compounds. Compounds are separated on an adsorbent paper (stationary phase) by their varied degree of solubility/mobility in the eluting solvent (mobile phase).Polyglutamic Acid: A peptide that is a homopolymer of glutamic acid.Autoantibodies: Antibodies that react with self-antigens (AUTOANTIGENS) of the organism that produced them.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.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.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.Lysine: An essential amino acid. It is often added to animal feed.Receptor-Like Protein Tyrosine Phosphatases, Class 8: A subclass of receptor-like protein tryosine phosphatases that contain an extracellular RDGS-adhesion recognition motif and a single cytosolic protein tyrosine phosphate domain.Kinetics: The rate dynamics in chemical or physical systems.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.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.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.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Isoenzymes: Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.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.Vitamin K: A lipid cofactor that is required for normal blood clotting. Several forms of vitamin K have been identified: VITAMIN K 1 (phytomenadione) derived from plants, VITAMIN K 2 (menaquinone) from bacteria, and synthetic naphthoquinone provitamins, VITAMIN K 3 (menadione). Vitamin K 3 provitamins, after being alkylated in vivo, exhibit the antifibrinolytic activity of vitamin K. Green leafy vegetables, liver, cheese, butter, and egg yolk are good sources of vitamin K.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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.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)Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.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.Molecular Weight: The sum of the weight of all the atoms in a molecule.Carbohydrates: The largest class of organic compounds, including STARCH; GLYCOGEN; CELLULOSE; POLYSACCHARIDES; and simple MONOSACCHARIDES. Carbohydrates are composed of carbon, hydrogen, and oxygen in a ratio of Cn(H2O)n.Autoantigens: Endogenous tissue constituents that have the ability to interact with AUTOANTIBODIES and cause an immune response.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).Carbon-Carbon Ligases: Enzymes that catalyze the joining of two molecules by the formation of a carbon-carbon bond. These are the carboxylating enzymes and are mostly biotinyl-proteins. EC 6.4.Chemistry: A basic science concerned with the composition, structure, and properties of matter; and the reactions that occur between substances and the associated energy exchange.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.Chemical Phenomena: The composition, conformation, and properties of atoms and molecules, and their reaction and interaction processes.Pimelic Acids: A group of compounds that are derivatives of heptanedioic acid with the general formula R-C7H11O4.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.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.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.1-Carboxyglutamic Acid: Found in various tissues, particularly in four blood-clotting proteins including prothrombin, in kidney protein, in bone protein, and in the protein present in various ectopic calcifications.Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.GlutaminaseSerine: 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.RNA, Transfer, Glu: A transfer RNA which is specific for carrying glutamic acid to sites on the ribosomes in preparation for protein synthesis.Histidine: An essential amino acid that is required for the production of HISTAMINE.Mice, Inbred NOD: A strain of non-obese diabetic mice developed in Japan that has been widely studied as a model for T-cell-dependent autoimmune insulin-dependent diabetes mellitus in which insulitis is a major histopathologic feature, and in which genetic susceptibility is strongly MHC-linked.Dystonia Musculorum Deformans: A condition characterized by focal DYSTONIA that progresses to involuntary spasmodic contractions of the muscles of the legs, trunk, arms, and face. The hands are often spared, however, sustained axial and limb contractions may lead to a state where the body is grossly contorted. Onset is usually in the first or second decade. Familial patterns of inheritance, primarily autosomal dominant with incomplete penetrance, have been identified. (Adams et al., Principles of Neurology, 6th ed, p1078)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.HexosaminesActinomycetales: An order of gram-positive, primarily aerobic BACTERIA that tend to form branching filaments.Arginine: An essential amino acid that is physiologically active in the L-form.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.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.Glutamate-tRNA Ligase: An enzyme that activates glutamic acid with its specific transfer RNA. EC 6.1.1.17.Carbon Isotopes: Stable carbon atoms that have the same atomic number as the element carbon, but differ in atomic weight. C-13 is a stable carbon isotope.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.Chromatography, Gel: Chromatography on non-ionic gels without regard to the mechanism of solute discrimination.Chromatography, High Pressure Liquid: Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Cell Wall: The outermost layer of a cell in most PLANTS; BACTERIA; FUNGI; and ALGAE. The cell wall is usually a rigid structure that lies external to the CELL MEMBRANE, and provides a protective barrier against physical or chemical agents.Neurons: The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the NERVOUS SYSTEM.Aspartate Aminotransferases: Enzymes of the transferase class that catalyze the conversion of L-aspartate and 2-ketoglutarate to oxaloacetate and L-glutamate. EC 2.6.1.1.Islets of Langerhans: Irregular microscopic structures consisting of cords of endocrine cells that are scattered throughout the PANCREAS among the exocrine acini. Each islet is surrounded by connective tissue fibers and penetrated by a network of capillaries. There are four major cell types. The most abundant beta cells (50-80%) secrete INSULIN. Alpha cells (5-20%) secrete GLUCAGON. PP cells (10-35%) secrete PANCREATIC POLYPEPTIDE. Delta cells (~5%) secrete SOMATOSTATIN.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.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.Parvalbumins: Low molecular weight, calcium binding muscle proteins. Their physiological function is possibly related to the contractile process.Insulin Antibodies: Antibodies specific to INSULIN.Pyrrolidonecarboxylic Acid: A cyclized derivative of L-GLUTAMIC ACID. Elevated blood levels may be associated with problems of GLUTAMINE or GLUTATHIONE metabolism.Bacillus: A genus of BACILLACEAE that are spore-forming, rod-shaped cells. Most species are saprophytic soil forms with only a few species being pathogenic.Vesicular Inhibitory Amino Acid Transport Proteins: A family of vesicular neurotransmitter transporter proteins that sequester the inhibitory neurotransmitters GLYCINE; GAMMA-AMINOBUTYRIC ACID; and possibly GAMMA-HYDROXYBUTYRATE into SECRETORY VESICLES.Chromatography, Ion Exchange: Separation technique in which the stationary phase consists of ion exchange resins. The resins contain loosely held small ions that easily exchange places with other small ions of like charge present in solutions washed over the resins.Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.Aminobutyrates: Derivatives of BUTYRIC ACID that contain one or more amino groups attached to the aliphatic structure. Included under this heading are a broad variety of acid forms, salts, esters, and amides that include the aminobutryrate structure.PeptidoglycanOrnithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine.4-Aminobutyrate Transaminase: An enzyme that converts brain gamma-aminobutyric acid (GAMMA-AMINOBUTYRIC ACID) into succinate semialdehyde, which can be converted to succinic acid and enter the citric acid cycle. It also acts on beta-alanine. EC 2.6.1.19.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).Oligopeptides: Peptides composed of between two and twelve amino acids.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.Chromatography: Techniques used to separate mixtures of substances based on differences in the relative affinities of the substances for mobile and stationary phases. A mobile phase (fluid or gas) passes through a column containing a stationary phase of porous solid or liquid coated on a solid support. Usage is both analytical for small amounts and preparative for bulk amounts.Bacterial Proteins: Proteins found in any species of bacterium.Berylliosis: A form of pneumoconiosis caused by inhaled rare metal BERYLLIUM or its soluble salts which are used in a wide variety of industry including alloys, ceramics, radiographic equipment, and vacuum tubes. Berylliosis is characterized by an acute inflammatory reaction in the upper airway leading to BRONCHIOLITIS; PULMONARY EDEMA; and pneumonia.Phosphorylation: The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.Epitopes: Sites on an antigen that interact with specific antibodies.Immunochemistry: Field of chemistry that pertains to immunological phenomena and the study of chemical reactions related to antigen stimulation of tissues. It includes physicochemical interactions between antigens and antibodies.Electrophoresis: An electrochemical process in which macromolecules or colloidal particles with a net electric charge migrate in a solution under the influence of an electric current.Hydrolysis: The process of cleaving a chemical compound by the addition of a molecule of water.Carboxylic Acids: Organic compounds containing the carboxy group (-COOH). This group of compounds includes amino acids and fatty acids. Carboxylic acids can be saturated, unsaturated, or aromatic.Co-Repressor Proteins: A subclass of repressor proteins that do not directly bind DNA. Instead, co-repressors generally act via their interaction with DNA-BINDING PROTEINS such as a TRANSCRIPTIONAL SILENCING FACTORS or NUCLEAR RECEPTORS.Glutamate-Ammonia Ligase: An enzyme that catalyzes the conversion of ATP, L-glutamate, and NH3 to ADP, orthophosphate, and L-glutamine. It also acts more slowly on 4-methylene-L-glutamate. (From Enzyme Nomenclature, 1992) EC 6.3.1.2.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)Amino Sugars: SUGARS containing an amino group. GLYCOSYLATION of other compounds with these amino sugars results in AMINOGLYCOSIDES.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.Culture Media: Any liquid or solid preparation made specifically for the growth, storage, or transport of microorganisms or other types of cells. The variety of media that exist allow for the culturing of specific microorganisms and cell types, such as differential media, selective media, test media, and defined media. Solid media consist of liquid media that have been solidified with an agent such as AGAR or GELATIN.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.GABA Plasma Membrane Transport Proteins: A family of plasma membrane neurotransmitter transporter proteins that regulates extracellular levels of the inhibitory neurotransmitter GAMMA-AMINOBUTYRIC ACID. They differ from GABA RECEPTORS, which signal cellular responses to GAMMA-AMINOBUTYRIC ACID. They control GABA reuptake into PRESYNAPTIC TERMINALS in the CENTRAL NERVOUS SYSTEM through high-affinity sodium-dependent transport.Cerebellar Ataxia: Incoordination of voluntary movements that occur as a manifestation of CEREBELLAR DISEASES. Characteristic features include a tendency for limb movements to overshoot or undershoot a target (dysmetria), a tremor that occurs during attempted movements (intention TREMOR), impaired force and rhythm of diadochokinesis (rapidly alternating movements), and GAIT ATAXIA. (From Adams et al., Principles of Neurology, 6th ed, p90)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.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.Glutamate Dehydrogenase: An enzyme that catalyzes the conversion of L-glutamate and water to 2-oxoglutarate and NH3 in the presence of NAD+. (From Enzyme Nomenclature, 1992) EC 1.4.1.2.Diaminopimelic AcidMass Spectrometry: An analytical method used in determining the identity of a chemical based on its mass using mass analyzers/mass spectrometers.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.Carboxy-Lyases: Enzymes that catalyze the addition of a carboxyl group to a compound (carboxylases) or the removal of a carboxyl group from a compound (decarboxylases). EC 4.1.1.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.Receptors, GABA: Cell-surface proteins that bind GAMMA-AMINOBUTYRIC ACID with high affinity and trigger changes that influence the behavior of cells. GABA-A receptors control chloride channels formed by the receptor complex itself. They are blocked by bicuculline and usually have modulatory sites sensitive to benzodiazepines and barbiturates. GABA-B receptors act through G-proteins on several effector systems, are insensitive to bicuculline, and have a high affinity for L-baclofen.HLA-DQ Antigens: A group of the D-related HLA antigens found to differ from the DR antigens in genetic locus and therefore inheritance. These antigens are polymorphic glycoproteins comprising alpha and beta chains and are found on lymphoid and other cells, often associated with certain diseases.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.HLA-DRB4 Chains: A subtype of HLA-DRB beta chains that is associated with the HLA-DR53 serological subtype.Ammonia: A colorless alkaline gas. It is formed in the body during decomposition of organic materials during a large number of metabolically important reactions. Note that the aqueous form of ammonia is referred to as AMMONIUM HYDROXIDE.Aconitum: A plant genus of the family RANUNCULACEAE. Members contain a number of diterpenoid alkaloids including: aconitans, hypaconitine, ACONITINE, jesaconitine, ignavine, napelline, and mesaconitine. The common name of Wolfbane is similar to the common name for ARNICA.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).)Vitamin K 2: A group of substances similar to VITAMIN K 1 which contains a ring of 2-methyl-1,4-naphthoquinione and an isoprenoid side chain of varying number of isoprene units. In vitamin K 2, each isoprene unit contains a double bond. They are produced by bacteria including the normal intestinal flora.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Paraneoplastic Polyneuropathy: A diffuse or multifocal peripheral neuropathy related to the remote effects of a neoplasm, most often carcinoma or lymphoma. Pathologically, there are inflammatory changes in peripheral nerves. The most common clinical presentation is a symmetric distal mixed sensorimotor polyneuropathy. (Adams et al., Principles of Neurology, 6th ed, p1334)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.Phenotype: The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.Rats, Sprague-Dawley: A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.Radioimmunosorbent Test: Radioimmunoassay of proteins using antibody coupled to an immunosorbent.Autoimmunity: Process whereby the immune system reacts against the body's own tissues. Autoimmunity may produce or be caused by AUTOIMMUNE DISEASES.Citrobacter: A genus of gram-negative, rod-shaped enterobacteria that can use citrate as the sole source of carbon.Brain: The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.Stereoisomerism: The phenomenon whereby compounds whose molecules have the same number and kind of atoms and the same atomic arrangement, but differ in their spatial relationships. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Fermentation: Anaerobic degradation of GLUCOSE or other organic nutrients to gain energy in the form of ATP. End products vary depending on organisms, substrates, and enzymatic pathways. Common fermentation products include ETHANOL and LACTIC ACID.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.Beryllium: Beryllium. An element with the atomic symbol Be, atomic number 4, and atomic weight 9.01218. Short exposure to this element can lead to a type of poisoning known as BERYLLIOSIS.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.Interneurons: Most generally any NEURONS which are not motor or sensory. Interneurons may also refer to neurons whose AXONS remain within a particular brain region in contrast to projection neurons, which have axons projecting to other brain regions.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).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 Mutational Analysis: Biochemical identification of mutational changes in a nucleotide sequence.Serine Endopeptidases: Any member of the group of ENDOPEPTIDASES containing at the active site a serine residue involved in catalysis.Vesicular Glutamate Transport Protein 2: A vesicular glutamate transporter protein that is predominately expressed in the DIENCEPHALON and lower brainstem regions of the CENTRAL NERVOUS SYSTEM.Nitrogen: An element with the atomic symbol N, atomic number 7, and atomic weight [14.00643; 14.00728]. Nitrogen exists as a diatomic gas and makes up about 78% of the earth's atmosphere by volume. It is a constituent of proteins and nucleic acids and found in all living cells.Chromatography, DEAE-Cellulose: A type of ion exchange chromatography using diethylaminoethyl cellulose (DEAE-CELLULOSE) as a positively charged resin. (From McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Nerve Tissue ProteinsEndopeptidases: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Protons: Stable elementary particles having the smallest known positive charge, found in the nuclei of all elements. The proton mass is less than that of a neutron. A proton is the nucleus of the light hydrogen atom, i.e., the hydrogen ion.DNA, Bacterial: Deoxyribonucleic acid that makes up the genetic material of bacteria.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Mutagenesis: Process of generating a genetic MUTATION. It may occur spontaneously or be induced by MUTAGENS.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.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.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.Choline O-Acetyltransferase: An enzyme that catalyzes the formation of acetylcholine from acetyl-CoA and choline. EC 2.3.1.6.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)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.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.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.Polyendocrinopathies, Autoimmune: Autoimmune diseases affecting multiple endocrine organs. Type I is characterized by childhood onset and chronic mucocutaneous candidiasis (CANDIDIASIS, CHRONIC MUCOCUTANEOUS), while type II exhibits any combination of adrenal insufficiency (ADDISON'S DISEASE), lymphocytic thyroiditis (THYROIDITIS, AUTOIMMUNE;), HYPOPARATHYROIDISM; and gonadal failure. In both types organ-specific ANTIBODIES against a variety of ENDOCRINE GLANDS have been detected. The type II syndrome differs from type I in that it is associated with HLA-A1 and B8 haplotypes, onset is usually in adulthood, and candidiasis is not present.Carrier Proteins: Transport proteins that carry specific substances in the blood or across cell membranes.Limbic Encephalitis: A paraneoplastic syndrome marked by degeneration of neurons in the LIMBIC SYSTEM. Clinical features include HALLUCINATIONS, loss of EPISODIC MEMORY; ANOSMIA; AGEUSIA; TEMPORAL LOBE EPILEPSY; DEMENTIA; and affective disturbance (depression). Circulating anti-neuronal antibodies (e.g., anti-Hu; anti-Yo; anti-Ri; and anti-Ma2) and small cell lung carcinomas or testicular carcinoma are frequently associated with this syndrome.Prothrombin: A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia.Receptors, GABA-A: Cell surface proteins which bind GAMMA-AMINOBUTYRIC ACID and contain an integral membrane chloride channel. Each receptor is assembled as a pentamer from a pool of at least 19 different possible subunits. The receptors belong to a superfamily that share a common CYSTEINE loop.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)Micromonosporaceae: A family of gram-positive, saprophytic bacteria occurring in soil and aquatic environments.HLA-DP beta-Chains: Transmembrane proteins that form the beta subunits of the HLA-DP antigens.GABAergic Neurons: Neurons whose primary neurotransmitter is GAMMA-AMINOBUTYRIC ACID.Cysteic Acid: Beta-Sulfoalanine. An amino acid with a C-terminal sulfonic acid group which has been isolated from human hair oxidized with permanganate. It occurs normally in the outer part of the sheep's fleece, where the wool is exposed to light and weather.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.Transaminases: A subclass of enzymes of the transferase class that catalyze the transfer of an amino group from a donor (generally an amino acid) to an acceptor (generally a 2-keto acid). Most of these enzymes are pyridoxyl phosphate proteins. (Dorland, 28th ed) EC 2.6.1.Corynebacterium: A genus of asporogenous bacteria that is widely distributed in nature. Its organisms appear as straight to slightly curved rods and are known to be human and animal parasites and pathogens.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.Glutamate Synthase: An enzyme that catalyzes the formation of 2 molecules of glutamate from glutamine plus alpha-ketoglutarate in the presence of NADPH. EC 1.4.1.13.Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)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.Models, Chemical: Theoretical representations that simulate the behavior or activity of chemical processes or phenomena; includes the use of mathematical equations, computers, and other electronic equipment.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.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Succinates: Derivatives of SUCCINIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain a 1,4-carboxy terminated aliphatic structure.Receptors, Ionotropic Glutamate: A class of ligand-gated ion channel receptors that have specificity for GLUTAMATE. They are distinct from METABOTROPIC GLUTAMATE RECEPTORS which act through a G-protein-coupled mechanism.Methionine: A sulfur-containing essential L-amino acid that is important in many body functions.Base Composition: The relative amounts of the PURINES and PYRIMIDINES in a nucleic acid.RNA, Ribosomal, 16S: Constituent of 30S subunit prokaryotic ribosomes containing 1600 nucleotides and 21 proteins. 16S rRNA is involved in initiation of polypeptide synthesis.DNA, Ribosomal: DNA sequences encoding RIBOSOMAL RNA and the segments of DNA separating the individual ribosomal RNA genes, referred to as RIBOSOMAL SPACER DNA.Protein Tyrosine Phosphatase, Non-Receptor Type 1: A subtype of non-receptor protein tyrosine phosphatases that includes two distinctive targeting motifs; an N-terminal motif specific for the INSULIN RECEPTOR, and a C-terminal motif specific for the SH3 domain containing proteins. This subtype includes a hydrophobic domain which localizes it to the ENDOPLASMIC RETICULUM.Immunohistochemistry: Histochemical localization of immunoreactive substances using labeled antibodies as reagents.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).HLA-DR Antigens: A subclass of HLA-D antigens that consist of alpha and beta chains. The inheritance of HLA-DR antigens differs from that of the HLA-DQ ANTIGENS and HLA-DP ANTIGENS.Pteroylpolyglutamic Acids: Derivatives of folic acid (pteroylglutamic acid). In gamma-glutamyl linkage they are found in many tissues. They are converted to folic acid by the action of pteroylpolyglutamate hydrolase or synthesized from folic acid by the action of folate polyglutamate synthetase. Synthetic pteroylpolyglutamic acids, which are in alpha-glutamyl linkage, are active in bacterial growth assays.Fluoroimmunoassay: The use of fluorescence spectrometry to obtain quantitative results for the FLUORESCENT ANTIBODY TECHNIQUE. One advantage over the other methods (e.g., radioimmunoassay) is its extreme sensitivity, with a detection limit on the order of tenths of microgram/liter.Ketoglutaric Acids: A family of compounds containing an oxo group with the general structure of 1,5-pentanedioic acid. (From Lehninger, Principles of Biochemistry, 1982, p442)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.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).Biotin: A water-soluble, enzyme co-factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk.Alicyclobacillus: A genus of GRAM-POSITIVE ENDOSPORE-FORMING RODS, in the family Alicyclobacillaceae, containing a unique lipid in their membranes.Dimerization: The process by which two molecules of the same chemical composition form a condensation product or polymer.Blotting, Western: Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.Dystonia: An attitude or posture due to the co-contraction of agonists and antagonist muscles in one region of the body. It most often affects the large axial muscles of the trunk and limb girdles. Conditions which feature persistent or recurrent episodes of dystonia as a primary manifestation of disease are referred to as DYSTONIC DISORDERS. (Adams et al., Principles of Neurology, 6th ed, p77)Amino Acyl-tRNA Synthetases: A subclass of enzymes that aminoacylate AMINO ACID-SPECIFIC TRANSFER RNA with their corresponding AMINO ACIDS.Tryptophan Synthase: An enzyme that catalyzes the conversion of L-serine and 1-(indol-3-yl)glycerol 3-phosphate to L-tryptophan and glyceraldehyde 3-phosphate. It is a pyridoxal phosphate protein that also catalyzes the conversion of serine and indole into tryptophan and water and of indoleglycerol phosphate into indole and glyceraldehyde phosphate. (From Enzyme Nomenclature, 1992) EC 4.2.1.20.Leucine: An essential branched-chain amino acid important for hemoglobin formation.