Procollagen: A biosynthetic precursor of collagen containing additional amino acid sequences at the amino-terminal and carboxyl-terminal ends of the polypeptide chains.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.Dioxygenases: Non-heme iron-containing enzymes that incorporate two atoms of OXYGEN into the substrate. They are important in biosynthesis of FLAVONOIDS; GIBBERELLINS; and HYOSCYAMINE; and for degradation of AROMATIC HYDROCARBONS.4-Hydroxyphenylpyruvate Dioxygenase: An enzyme that catalyzes the conversion of 4-hydroxyphenylpyruvate plus oxygen to homogentisic acid and carbon dioxide. EC Oxidases that specifically introduce DIOXYGEN-derived oxygen atoms into a variety of organic molecules.Catechol 2,3-Dioxygenase: Catalyzes the oxidation of catechol to 2-hydroxymuconate semialdehyde in the carbazole and BENZOATE degradation via HYDROXYLATION pathways. It also catalyzes the conversion of 3-methylcatechol to cis, cis-2-hydroxy-6-oxohept-2,4-dienoate in the TOLUENE and XYLENE degradation pathway. This enzyme was formerly characterized as EC,4-Dioxygenase: An enzyme that catalyzes the oxidation of protocatechuate to 3-carboxy-cis-cis-muconate in the presence of molecular oxygen. It contains ferric ion. EC Dioxygenase: An enzyme that catalyzes the conversion of L-CYSTEINE to 3-sulfinoalanine (3-sulfino-L-alanine) in the CYSTEINE metabolism and TAURINE and hypotaurine metabolic pathways.Proline Oxidase: The first enzyme of the proline degradative pathway. It catalyzes the oxidation of proline to pyrroline-5-carboxylic acid in the presence of oxygen and water. The action is not reversible. The specific activity of proline oxidase increases with age. EC 1.5.3.-.Catechol 1,2-Dioxygenase: An enzyme that catalyzes the oxidation of catechol to muconic acid with the use of Fe3+ as a cofactor. This enzyme was formerly characterized as EC and EC N-Endopeptidase: An extracellular endopeptidase which excises a block of peptides at the amino terminal, nonhelical region of the procollagen molecule with the formation of collagen. Absence or deficiency of the enzyme causes accumulation of procollagen which results in the inherited connective tissue disorder--dermatosparaxis. EC Oxygenase: A dioxygenase with specificity for the oxidation of the indoleamine ring of TRYPTOPHAN. It is a LIVER-specific enzyme that is the first and rate limiting enzyme in the kynurenine pathway of TRYPTOPHAN catabolism.Homogentisate 1,2-Dioxygenase: A mononuclear Fe(II)-dependent oxygenase, this enzyme catalyzes the conversion of homogentisate to 4-maleylacetoacetate, the third step in the pathway for the catabolism of TYROSINE. Deficiency in the enzyme causes ALKAPTONURIA, an autosomal recessive disorder, characterized by homogentisic aciduria, OCHRONOSIS and ARTHRITIS. This enzyme was formerly characterized as EC and EC 3,4-Dioxygenase: An enzyme that catalyzes the conversion of 3-hydroxyanthranilate to 2-amino-3-carboxymuconate semialdehyde. It was formerly characterized as EC Morphogenetic Protein 1: A bone morphogenetic protein family member that includes an active tolloid-like metalloproteinase domain. The metalloproteinase activity of bone morphogenetic protein 1 is specific for the removal of the C-propeptide of PROCOLLAGEN and may act as a regulator of EXTRACELLULAR MATRIX deposition. Alternative splicing of MRNA for bone morphogenetic protein 1 results in the production of several PROTEIN ISOFORMS.KynurenineCollagen: A polypeptide substance comprising about one third of the total protein in mammalian organisms. It is the main constituent of SKIN; CONNECTIVE TISSUE; and the organic substance of bones (BONE AND BONES) and teeth (TOOTH).Catechols: A group of 1,2-benzenediols that contain the general formula R-C6H5O2.Pseudomonas: A genus of gram-negative, aerobic, rod-shaped bacteria widely distributed in nature. Some species are pathogenic for humans, animals, and plants.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.Biodegradation, Environmental: Elimination of ENVIRONMENTAL POLLUTANTS; PESTICIDES and other waste using living organisms, usually involving intervention of environmental or sanitation engineers.Osteogenesis Imperfecta: COLLAGEN DISEASES characterized by brittle, osteoporotic, and easily fractured bones. It may also present with blue sclerae, loose joints, and imperfect dentin formation. Most types are autosomal dominant and are associated with mutations in COLLAGEN TYPE I.HSP47 Heat-Shock Proteins: Basic glycoprotein members of the SERPIN SUPERFAMILY that function as COLLAGEN-specific MOLECULAR CHAPERONES in the ENDOPLASMIC RETICULUM.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.Ehlers-Danlos Syndrome: A heterogeneous group of autosomally inherited COLLAGEN DISEASES caused by defects in the synthesis or structure of FIBRILLAR COLLAGEN. There are numerous subtypes: classical, hypermobility, vascular, and others. Common clinical features include hyperextensible skin and joints, skin fragility and reduced wound healing capability.2,2'-Dipyridyl: A reagent used for the determination of iron.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.Collagen Type I: The most common form of fibrillar collagen. It is a major constituent of bone (BONE AND BONES) and SKIN and consists of a heterotrimer of two alpha1(I) and one alpha2(I) chains.Procollagen-Proline Dioxygenase: A mixed-function oxygenase that catalyzes the hydroxylation of a prolyl-glycyl containing peptide, usually in PROTOCOLLAGEN, to a hydroxyprolylglycyl-containing-peptide. The enzyme utilizes molecular OXYGEN with a concomitant oxidative decarboxylation of 2-oxoglutarate to SUCCINATE. The enzyme occurs as a tetramer of two alpha and two beta subunits. The beta subunit of procollagen-proline dioxygenase is identical to the enzyme PROTEIN DISULFIDE-ISOMERASES.Pyrroline Carboxylate Reductases: A group of enzymes that catalyze the reduction of 1-pyrroline carboxylate to proline in the presence of NAD(P)H. Includes both the 2-oxidoreductase (EC and the 5-oxidoreductase (EC The former also reduces 1-piperidine-2-carboxylate to pipecolate and the latter also reduces 1-pyrroline-3-hydroxy-5-carboxylate to hydroxyproline.Hydroxyproline: A hydroxylated form of the imino acid proline. A deficiency in ASCORBIC ACID can result in impaired hydroxyproline formation.Rhodococcus: A bacterial genus of the order ACTINOMYCETALES.Pseudomonas putida: A species of gram-negative, aerobic bacteria isolated from soil and water as well as clinical specimens. Occasionally it is an opportunistic pathogen.Fibroblasts: Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.Collagen Type III: A fibrillar collagen consisting of three identical alpha1(III) chains that is widely distributed in many tissues containing COLLAGEN TYPE I. It is particularly abundant in BLOOD VESSELS and may play a role in tissues with elastic characteristics.Substrate Specificity: A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.Base Sequence: The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.1-Pyrroline-5-Carboxylate Dehydrogenase: An enzyme that catalyzes the oxidation of 1-pyrroline-5-carboxylate to L-GLUTAMATE in the presence of NAD. Defects in the enzyme are the cause of hyperprolinemia II.Microbial Collagenase: A metalloproteinase which degrades helical regions of native collagen to small fragments. Preferred cleavage is -Gly in the sequence -Pro-Xaa-Gly-Pro-. Six forms (or 2 classes) have been isolated from Clostridium histolyticum that are immunologically cross-reactive but possess different sequences and different specificities. Other variants have been isolated from Bacillus cereus, Empedobacter collagenolyticum, Pseudomonas marinoglutinosa, and species of Vibrio and Streptomyces. EC A genus of gram-negative, aerobic, rod-shaped bacteria characterized by an outer membrane that contains glycosphingolipids but lacks lipopolysaccharide. They have the ability to degrade a broad range of substituted aromatic compounds.Kinetics: The rate dynamics in chemical or physical systems.Burkholderia: A genus of gram-negative, aerobic, rod-shaped bacteria. Organisms in this genus had originally been classified as members of the PSEUDOMONAS genus but overwhelming biochemical and chemical findings indicated the need to separate them from other Pseudomonas species, and hence, this new genus was created.Tolloid-Like Metalloproteinases: A family of metalloproteases that are related to the DROSOPHILA protein tolloid, which is a gene product necessary for dorsal-ventral patterning in early Drosophila embryogenesis. Many members of the group may play a significant role in intercellular signaling.Peptide Fragments: Partial proteins formed by partial hydrolysis of complete proteins or generated through PROTEIN ENGINEERING techniques.Tendons: Fibrous bands or cords of CONNECTIVE TISSUE at the ends of SKELETAL MUSCLE FIBERS that serve to attach the MUSCLES to bones and other structures.Comamonas: A genus of gram-negative, straight or slightly curved rods which are motile by polar flagella and which accumulate poly-beta-hydroxybutyrate within the cells.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.Chick Embryo: The developmental entity of a fertilized chicken egg (ZYGOTE). The developmental process begins about 24 h before the egg is laid at the BLASTODISC, a small whitish spot on the surface of the EGG YOLK. After 21 days of incubation, the embryo is fully developed before hatching.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.Mixed Function Oxygenases: Widely distributed enzymes that carry out oxidation-reduction reactions in which one atom of the oxygen molecule is incorporated into the organic substrate; the other oxygen atom is reduced and combined with hydrogen ions to form water. They are also known as monooxygenases or hydroxylases. These reactions require two substrates as reductants for each of the two oxygen atoms. There are different classes of monooxygenases depending on the type of hydrogen-providing cosubstrate (COENZYMES) required in the mixed-function oxidation.Homogentisic AcidSkin: The outer covering of the body that protects it from the environment. It is composed of the DERMIS and the EPIDERMIS.Chlorobenzoates: Benzoic acid or benzoic acid esters substituted with one or more chlorine atoms.Hydroxylation: Placing of a hydroxyl group on a compound in a position where one did not exist before. (Stedman, 26th ed)Amino Acid Transport Systems, Neutral: Amino acid transporter systems capable of transporting neutral amino acids (AMINO ACIDS, NEUTRAL).Toluene: A widely used industrial solvent.Pepsin A: Formed from pig pepsinogen by cleavage of one peptide bond. The enzyme is a single polypeptide chain and is inhibited by methyl 2-diaazoacetamidohexanoate. It cleaves peptides preferentially at the carbonyl linkages of phenylalanine or leucine and acts as the principal digestive enzyme of gastric juice.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.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.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.Recombinant Proteins: Proteins prepared by recombinant DNA technology.Fibril-Associated Collagens: A family of non-fibrillar collagens that interact with FIBRILLAR COLLAGENS. They contain short triple helical domains interrupted by short non-helical domains and do not form into collagen fibrils.Hydroxybenzoates: Benzoate derivatives substituted by one or more hydroxy groups in any position on the benzene ring.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).Electrophoresis, Polyacrylamide Gel: Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.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.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.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, Bacterial: The functional hereditary units of BACTERIA.Burkholderiaceae: A family of gram negative, aerobic, non-sporeforming, rod-shaped bacteria.3-Hydroxyanthranilic Acid: An oxidation product of tryptophan metabolism. It may be a free radical scavenger and a carcinogen.gamma-Butyrobetaine Dioxygenase: An enzyme that catalyzes the HYDROXYLATION of gamma-butyrobetaine to L-CARNITINE. It is the last enzyme in the biosynthetic pathway of L-CARNITINE and is dependent on alpha-ketoglutarate; IRON; ASCORBIC ACID; and OXYGEN.Alkaptonuria: An inborn error of amino acid metabolism resulting from a defect in the enzyme HOMOGENTISATE 1,2-DIOXYGENASE, an enzyme involved in the breakdown of PHENYLALANINE and TYROSINE. It is characterized by accumulation of HOMOGENTISIC ACID in the urine, OCHRONOSIS in various tissues, and ARTHRITIS.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.Gentisates: Salts and esters of gentisic acid.Polychlorinated Biphenyls: Industrial products consisting of a mixture of chlorinated biphenyl congeners and isomers. These compounds are highly lipophilic and tend to accumulate in fat stores of animals. Many of these compounds are considered toxic and potential environmental pollutants.Brevibacterium: A gram-positive organism found in dairy products, fresh and salt water, marine organisms, insects, and decaying organic matter.Skin Aging: The process of aging due to changes in the structure and elasticity of the skin over time. It may be a part of physiological aging or it may be due to the effects of ultraviolet radiation, usually through exposure to sunlight.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.Oxidation-Reduction: A chemical reaction in which an electron is transferred from one molecule to another. The electron-donating molecule is the reducing agent or reductant; the electron-accepting molecule is the oxidizing agent or oxidant. Reducing and oxidizing agents function as conjugate reductant-oxidant pairs or redox pairs (Lehninger, Principles of Biochemistry, 1982, p471).Ferredoxins: Iron-containing proteins that transfer electrons, usually at a low potential, to flavoproteins; the iron is not present as in heme. (McGraw-Hill Dictionary of Scientific and Technical Terms, 5th ed)Molecular Weight: The sum of the weight of all the atoms in a molecule.Bacterial Proteins: Proteins found in any species of bacterium.Glutamate-5-Semialdehyde Dehydrogenase: An NADP+ dependent enzyme that catalyzes the oxidation of L-glutamate 5-semialdehyde to L-glutamyl 5-phosphate. It plays a role in the urea cycle and metabolism of amino groups.Procollagen-Lysine, 2-Oxoglutarate 5-Dioxygenase: A mixed-function oxygenase that catalyzes the hydroxylation of peptidyllysine, usually in protocollagen, to peptidylhydroxylysine. The enzyme utilizes molecular oxygen with concomitant oxidative decarboxylation of the cosubstrate 2-oxoglutarate to succinate. EC A genus of asporogenous bacteria isolated from soil that displays a distinctive rod-coccus growth cycle.Sulfanilic Acids: Aminobenzenesulfonic acids. Organic acids that are used in the manufacture of dyes and organic chemicals and as reagents.Models, Molecular: Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.Alcaligenes: A genus of gram-negative, aerobic, motile bacteria that occur in water and soil. Some are common inhabitants of the intestinal tract of vertebrates. These bacteria occasionally cause opportunistic infections in humans.Cartilage: A non-vascular form of connective tissue composed of CHONDROCYTES embedded in a matrix that includes CHONDROITIN SULFATE and various types of FIBRILLAR COLLAGEN. There are three major types: HYALINE CARTILAGE; FIBROCARTILAGE; and ELASTIC CARTILAGE.Iron-Sulfur Proteins: A group of proteins possessing only the iron-sulfur complex as the prosthetic group. These proteins participate in all major pathways of electron transport: photosynthesis, respiration, hydroxylation and bacterial hydrogen and nitrogen fixation.Binding Sites: The parts of a macromolecule that directly participate in its specific combination with another molecule.Metalloendopeptidases: ENDOPEPTIDASES which use a metal such as ZINC in the catalytic mechanism.Quinolinic Acid: A metabolite of tryptophan with a possible role in neurodegenerative disorders. Elevated CSF levels of quinolinic acid are correlated with the severity of neuropsychological deficits in patients who have AIDS.Iron: A metallic element with atomic symbol Fe, atomic number 26, and atomic weight 55.85. It is an essential constituent of HEMOGLOBINS; CYTOCHROMES; and IRON-BINDING PROTEINS. It plays a role in cellular redox reactions and in the transport of OXYGEN.Delftia acidovorans: A species of gram-negative rod-shaped bacteria found ubiquitously and formerly called Comamonas acidovorans and Pseudomonas acidovorans. It is the type species of the genus DELFTIA.Hydrocarbons, Aromatic: Organic compounds containing carbon and hydrogen in the form of an unsaturated, usually hexagonal ring structure. The compounds can be single ring, or double, triple, or multiple fused rings.Extracellular Matrix: A meshwork-like substance found within the extracellular space and in association with the basement membrane of the cell surface. It promotes cellular proliferation and provides a supporting structure to which cells or cell lysates in culture dishes adhere.Sorbic Acid: Mold and yeast inhibitor. Used as a fungistatic agent for foods, especially cheeses.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.Bone and Bones: A specialized CONNECTIVE TISSUE that is the main constituent of the SKELETON. The principle cellular component of bone is comprised of OSTEOBLASTS; OSTEOCYTES; and OSTEOCLASTS, while FIBRILLAR COLLAGENS and hydroxyapatite crystals form the BONE MATRIX.Biphenyl CompoundsBenzoates: Derivatives of BENZOIC ACID. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxybenzene structure.PhenanthrenesPhosphotransferases (Carboxyl Group Acceptor): A class of enzymes that transfers phosphate groups and has a carboxyl group as an acceptor. EC 2.7.2.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.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.Ascorbic Acid: A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant.Cell Line: Established cell cultures that have the potential to propagate indefinitely.Azetidinecarboxylic Acid: A proline analog that acts as a stoichiometric replacement of proline. It causes the production of abnormal proteins with impaired biological activity.Protein Precursorsbeta-Carotene 15,15'-Monooxygenase: A monooxygenase that catalyzes the conversion of BETA-CAROTENE into two molecules of RETINAL. It was formerly characterized as EC and EC A group of disorders which have in common elevations of tyrosine in the blood and urine secondary to an enzyme deficiency. Type I tyrosinemia features episodic weakness, self-mutilation, hepatic necrosis, renal tubular injury, and seizures and is caused by a deficiency of the enzyme fumarylacetoacetase. Type II tyrosinemia features INTELLECTUAL DISABILITY, painful corneal ulcers, and keratoses of the palms and plantar surfaces and is caused by a deficiency of the enzyme TYROSINE TRANSAMINASE. Type III tyrosinemia features INTELLECTUAL DISABILITY and is caused by a deficiency of the enzyme 4-HYDROXYPHENYLPYRUVATE DIOXYGENASE. (Menkes, Textbook of Child Neurology, 5th ed, pp42-3)Ferrous Compounds: Inorganic or organic compounds that contain divalent iron.Nucleic Acid Hybridization: Widely used technique which exploits the ability of complementary sequences in single-stranded DNAs or RNAs to pair with each other to form a double helix. Hybridization can take place between two complimentary DNA sequences, between a single-stranded DNA and a complementary RNA, or between two RNA sequences. The technique is used to detect and isolate specific sequences, measure homology, or define other characteristics of one or both strands. (Kendrew, Encyclopedia of Molecular Biology, 1994, p503)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.Enzyme Induction: An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.Benzoic Acid: A fungistatic compound that is widely used as a food preservative. It is conjugated to GLYCINE in the liver and excreted as hippuric acid.Gene Expression: The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.Extracellular Matrix Proteins: Macromolecular organic compounds that contain carbon, hydrogen, oxygen, nitrogen, and usually, sulfur. These macromolecules (proteins) form an intricate meshwork in which cells are embedded to construct tissues. Variations in the relative types of macromolecules and their organization determine the type of extracellular matrix, each adapted to the functional requirements of the tissue. The two main classes of macromolecules that form the extracellular matrix are: glycosaminoglycans, usually linked to proteins (proteoglycans), and fibrous proteins (e.g., COLLAGEN; ELASTIN; FIBRONECTINS; and LAMININ).Fibrosis: Any pathological condition where fibrous connective tissue invades any organ, usually as a consequence of inflammation or other injury.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).Mutagenesis, Site-Directed: Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.Endopeptidases: A subclass of PEPTIDE HYDROLASES that catalyze the internal cleavage of PEPTIDES or PROTEINS.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.Restriction Mapping: Use of restriction endonucleases to analyze and generate a physical map of genomes, genes, or other segments of DNA.2,4-Dichlorophenoxyacetic Acid: An herbicide with irritant effects on the eye and the gastrointestinal system.Sequence Analysis, DNA: A multistage process that includes cloning, physical mapping, subcloning, determination of the DNA SEQUENCE, and information analysis.Ralstonia: A genus in the family BURKHOLDERIACEAE, comprised of many species. They are associated with a variety of infections including MENINGITIS; PERITONITIS; and URINARY TRACT INFECTIONS.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.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.Trichloroethylene: A highly volatile inhalation anesthetic used mainly in short surgical procedures where light anesthesia with good analgesia is required. It is also used as an industrial solvent. Prolonged exposure to high concentrations of the vapor can lead to cardiotoxicity and neurological impairment.Pseudomonas pseudoalcaligenes: A species of gram-negative bacteria in the genus PSEUDOMONAS. All strains can utilize FRUCTOSE for energy. It is occasionally isolated from humans and some strains are pathogenic to WATERMELON.Naphthalenes: Two-ring crystalline hydrocarbons isolated from coal tar. They are used as intermediates in chemical synthesis, as insect repellents, fungicides, lubricants, preservatives, and, formerly, as topical antiseptics.Cysteine: A thiol-containing non-essential amino acid that is oxidized to form CYSTINE.Collagen Diseases: Historically, a heterogeneous group of acute and chronic diseases, including rheumatoid arthritis, systemic lupus erythematosus, progressive systemic sclerosis, dermatomyositis, etc. This classification was based on the notion that "collagen" was equivalent to "connective tissue", but with the present recognition of the different types of collagen and the aggregates derived from them as distinct entities, the term "collagen diseases" now pertains exclusively to those inherited conditions in which the primary defect is at the gene level and affects collagen biosynthesis, post-translational modification, or extracellular processing directly. (From Cecil Textbook of Medicine, 19th ed, p1494)Crystallography, X-Ray: The study of crystal structure using X-RAY DIFFRACTION techniques. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed)Phenol: An antiseptic and disinfectant aromatic alcohol.Oxygen: An element with atomic symbol O, atomic number 8, and atomic weight [15.99903; 15.99977]. It is the most abundant element on earth and essential for respiration.Bone Morphogenetic Proteins: Bone-growth regulatory factors that are members of the transforming growth factor-beta superfamily of proteins. They are synthesized as large precursor molecules which are cleaved by proteolytic enzymes. The active form can consist of a dimer of two identical proteins or a heterodimer of two related bone morphogenetic proteins.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.Catalysis: The facilitation of a chemical reaction by material (catalyst) that is not consumed by the reaction.Benzene DerivativesVanillic Acid: A flavoring agent. It is the intermediate product in the two-step bioconversion of ferulic acid to vanillin. (J Biotechnol 1996;50(2-3):107-13).Fibrillar Collagens: A family of structurally related collagens that form the characteristic collagen fibril bundles seen in CONNECTIVE TISSUE.Acinetobacter: A genus of gram-negative bacteria of the family MORAXELLACEAE, found in soil and water and of uncertain pathogenicity.Parabens: Methyl, propyl, butyl, and ethyl esters of p-hydroxybenzoic acid. They have been approved by the FDA as antimicrobial agents for foods and pharmaceuticals. (From Hawley's Condensed Chemical Dictionary, 11th ed, p872)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)Liver Cirrhosis, Experimental: Experimentally induced chronic injuries to the parenchymal cells in the liver to achieve a model for LIVER CIRRHOSIS.Gram-Negative Aerobic Bacteria: A large group of aerobic bacteria which show up as pink (negative) when treated by the gram-staining method. This is because the cell walls of gram-negative bacteria are low in peptidoglycan and thus have low affinity for violet stain and high affinity for the pink dye safranine.Biological Markers: Measurable and quantifiable biological parameters (e.g., specific enzyme concentration, specific hormone concentration, specific gene phenotype distribution in a population, presence of biological substances) which serve as indices for health- and physiology-related assessments, such as disease risk, psychiatric disorders, environmental exposure and its effects, disease diagnosis, metabolic processes, substance abuse, pregnancy, cell line development, epidemiologic studies, etc.Multienzyme Complexes: Systems of enzymes which function sequentially by catalyzing consecutive reactions linked by common metabolic intermediates. They may involve simply a transfer of water molecules or hydrogen atoms and may be associated with large supramolecular structures such as MITOCHONDRIA or RIBOSOMES.Microscopy, Electron: Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen.Liver: A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.Electron Spin Resonance Spectroscopy: A technique applicable to the wide variety of substances which exhibit paramagnetism because of the magnetic moments of unpaired electrons. The spectra are useful for detection and identification, for determination of electron structure, for study of interactions between molecules, and for measurement of nuclear spins and moments. (From McGraw-Hill Encyclopedia of Science and Technology, 7th edition) Electron nuclear double resonance (ENDOR) spectroscopy is a variant of the technique which can give enhanced resolution. Electron spin resonance analysis can now be used in vivo, including imaging applications such as MAGNETIC RESONANCE IMAGING.Betaine: A naturally occurring compound that has been of interest for its role in osmoregulation. As a drug, betaine hydrochloride has been used as a source of hydrochloric acid in the treatment of hypochlorhydria. Betaine has also been used in the treatment of liver disorders, for hyperkalemia, for homocystinuria, and for gastrointestinal disturbances. (From Martindale, The Extra Pharmacopoeia, 30th ed, p1341)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.Collagen Type II: A fibrillar collagen found predominantly in CARTILAGE and vitreous humor. It consists of three identical alpha1(II) chains.Spectrophotometry: The art or process of comparing photometrically the relative intensities of the light in different parts of the spectrum.Amino Acid Isomerases: Enzymes that catalyze either the racemization or epimerization of chiral centers within amino acids or derivatives. EC 5.1.1.Oxidoreductases: The class of all enzymes catalyzing oxidoreduction reactions. The substrate that is oxidized is regarded as a hydrogen donor. The systematic name is based on donor:acceptor oxidoreductase. The recommended name will be dehydrogenase, wherever this is possible; as an alternative, reductase can be used. Oxidase is only used in cases where O2 is the acceptor. (Enzyme Nomenclature, 1992, p9)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)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.Gene Expression Regulation: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.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.Burkholderia cepacia: A species of BURKHOLDERIA considered to be an opportunistic human pathogen. It has been associated with various types of infections of nosocomial origin.Adipates: Derivatives of adipic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain a 1,6-carboxy terminated aliphatic structure.Kynurenine 3-Monooxygenase: An NADPH-dependent flavin monooxygenase that plays a key role in the catabolism of TRYPTOPHAN by catalyzing the HYDROXYLATION of KYNURENINE to 3-hydroxykynurenine. It was formerly characterized as EC and EC The major interferon produced by mitogenically or antigenically stimulated LYMPHOCYTES. It is structurally different from TYPE I INTERFERON and its major activity is immunoregulation. It has been implicated in the expression of CLASS II HISTOCOMPATIBILITY ANTIGENS in cells that do not normally produce them, leading to AUTOIMMUNE DISEASES.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.Nonheme Iron Proteins: Proteins, usually acting in oxidation-reduction reactions, containing iron but no porphyrin groups. (Lehninger, Principles of Biochemistry, 1993, pG-10)Keloid: A sharply elevated, irregularly shaped, progressively enlarging scar resulting from formation of excessive amounts of collagen in the dermis during connective tissue repair. It is differentiated from a hypertrophic scar (CICATRIX, HYPERTROPHIC) in that the former does not spread to surrounding tissues.Transforming Growth Factor beta: A factor synthesized in a wide variety of tissues. It acts synergistically with TGF-alpha in inducing phenotypic transformation and can also act as a negative autocrine growth factor. TGF-beta has a potential role in embryonal development, cellular differentiation, hormone secretion, and immune function. TGF-beta is found mostly as homodimer forms of separate gene products TGF-beta1, TGF-beta2 or TGF-beta3. Heterodimers composed of TGF-beta1 and 2 (TGF-beta1.2) or of TGF-beta2 and 3 (TGF-beta2.3) have been isolated. The TGF-beta proteins are synthesized as precursor proteins.Oxygen Isotopes: Stable oxygen atoms that have the same atomic number as the element oxygen, but differ in atomic weight. O-17 and 18 are stable oxygen isotopes.Taurine: A conditionally essential nutrient, important during mammalian development. It is present in milk but is isolated mostly from ox bile and strongly conjugates bile acids.Connective Tissue: Tissue that supports and binds other tissues. It consists of CONNECTIVE TISSUE CELLS embedded in a large amount of EXTRACELLULAR MATRIX.DNA, Bacterial: Deoxyribonucleic acid that makes up the genetic material of bacteria.Glycoproteins: Conjugated protein-carbohydrate compounds including mucins, mucoid, and amyloid glycoproteins.Chromatography, Gel: Chromatography on non-ionic gels without regard to the mechanism of solute discrimination.Gram-Negative Aerobic Rods and Cocci: A group of gram-negative bacteria consisting of rod- and coccus-shaped cells. They are both aerobic (able to grow under an air atmosphere) and microaerophilic (grow better in low concentrations of oxygen) under nitrogen-fixing conditions but, when supplied with a source of fixed nitrogen, they grow as aerobes.Disulfides: Chemical groups containing the covalent disulfide bonds -S-S-. The sulfur atoms can be bound to inorganic or organic moieties.Time Factors: Elements of limited time intervals, contributing to particular results or situations.Comb and Wattles: Fleshy and reddish outgrowth of skin tissue found on top of the head, attached to the sides of the head, and hanging from the mandible of birds such as turkeys and chickens.Catalytic Domain: The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.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)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.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.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.Ornithine: An amino acid produced in the urea cycle by the splitting off of urea from arginine.Phylogeny: The relationships of groups of organisms as reflected by their genetic makeup.Dipeptidases: EXOPEPTIDASES that specifically act on dipeptides. EC 3.4.13.Hydrolases: Any member of the class of enzymes that catalyze the cleavage of the substrate and the addition of water to the resulting molecules, e.g., ESTERASES, glycosidases (GLYCOSIDE HYDROLASES), lipases, NUCLEOTIDASES, peptidases (PEPTIDE HYDROLASES), and phosphatases (PHOSPHORIC MONOESTER HYDROLASES). EC 3.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)Lung: Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.Gene Expression Regulation, Enzymologic: Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.Osteocalcin: Vitamin K-dependent calcium-binding protein synthesized by OSTEOBLASTS and found primarily in BONES. Serum osteocalcin measurements provide a noninvasive specific marker of bone metabolism. The protein contains three residues of the amino acid gamma-carboxyglutamic acid (Gla), which, in the presence of CALCIUM, promotes binding to HYDROXYAPATITE and subsequent accumulation in BONE MATRIX.ortho-Aminobenzoates: Benzoic acids, salts, or esters that contain an amino group attached to carbon number 2 or 6 of the benzene ring structure.Comamonadaceae: A family of gram-negative aerobic bacteria in the class BETA PROTEOBACTERIA, encompassing the acidovorans rRNA complex. Some species are pathogenic for PLANTS.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.Collagen Type V: A fibrillar collagen found widely distributed as a minor component in tissues that contain COLLAGEN TYPE I and COLLAGEN TYPE III. It is a heterotrimeric molecule composed of alpha1(V), alpha2(V) and alpha3(V) subunits. Several forms of collagen type V exist depending upon the composition of the subunits that form the trimer.