Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.24.3 (collagenase)
18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Collagen type X is composed of three identical alpha 1(X) chains of 59 kDa, each containing a triple-helical region of 45 kDa flanked by a short N-terminal sequence and a larger non-collagenous C-terminal (NC1) domain of approx. 15 kDa. Collagen type X molecules can associate via their C-termini to form a regular hexagonal lattice in vitro, which in vivo may provide a modified extracellular matrix for the events of endochondral ossification. The NC1 domain of chick collagen type X was isolated and purified from a highly purified bacterial collagenase digest of hypertrophic chondrocyte medium proteins. The structure and aggregation properties of the NC1 domain of collagen X were investigated, independently of the triple helix. A trimer, a dimer and a monomer of the individual alpha-chain NC1 polypeptides were identified from a bacterial collagenase digest of cartilage collagens using [14C]tyrosine labelling, N-chlorosuccinimide peptide mapping and N-terminal sequencing. The trimer (50 kDa) remained intact in Laemmli sample buffer unless boiled, upon which it dissociated into the dimer (38 kDa) and the monomer (20 kDa). The dimer persisted even after prolonged periods of heating or reduction with beta-mercaptoethanol, and in preparations obtained from chondrocyte cultures treated with beta-aminoproprionitrile, indicating the presence of non-reducible, non-lysine-derived, covalent cross-links. Hexamers of the individual C-termini were observed in rotary-shadowed preparations of purified NC1 domain, reflecting the ability of collagen type X to self-assemble via its C-termini under appropriate conditions.
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PMID:Partial characterization of the C-terminal non-collagenous domain (NC1) of collagen type X. 897 56

A critical outcome of periodontal disease is degradation of the collagenous periodontal ligament that connects teeth to bone in the dental arch. Periodontal diseases occur in response to bacterial colonization of the teeth, but their molecular pathogenesis is still speculative. One family of enzymes, known as the matrix metalloproteinases (MMPs), has been implicated in the degradation of the periodontal ligament. MMPs, which are also suspected to play a role in many other physiologic and pathologic remodeling processes, can be secreted by epithelial cells surrounding the teeth and are found in relative abundance in tissues and fluids near periodontally diseased sites. Since most MMPs are secreted as inactive zymogens which may be activated by limited proteolysis, it has been suggested that proteinases expressed by the infecting periodontal pathogens might activate latent host MMPs to initiate or accelerate degradation of the collegenous periodontal ligament. The aim of this work was to examine interactions between purified host MMPs and bacterial proteinase. In this article, we demonstrate that a proteinase isolated from the periodontopathogen Porphyromonas gingivalis can activate MMP-1, MMP-3, and MMP-9 and can catalyze the superactivation of MMP-1 by MMP-3. Activation of these MMPs is demonstrated to result from initial hydrolysis within their propeptide. Also, for MMP-1 and MMP-9, the P. gingivalis proteinase cleaves the MMP propeptide following a lysine residue at a previously unreported site which, for both MMPs, is one residue NH2-terminal to the known autocatalytic cleavage site. These data describe a mode of virulence for the periodontopathogen Porphyromonas gingivalis that involves activation of host-degradative enzymes.
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PMID:Activation and novel processing of matrix metalloproteinases by a thiol-proteinase from the oral anaerobe Porphyromonas gingivalis. 916 59

The biological functions of rat surfactant protein A (SP-A), an oligomer composed of 18 polypeptide subunits derived from a single gene, are dependent on intact disulfide bonds. Reducible and collagenase-reversible covalent linkages of as many as six or more subunits in the molecule indicate the presence of at least two NH2-terminal interchain disulfide bonds. However, the reported primary structure of rat SP-A predicts that only Cys6 in this region is available for interchain disulfide formation. Direct evidence for a second disulfide bridge was obtained by analyses of a set of three mutant SP-As with telescoping deletions from the reported NH2-terminus. Two of the truncated recombinant proteins formed reducible dimers despite deletion of the domain containing Cys6. Edman degradation revealed that each mutant protein was a mixture of two isoforms with and without an isoleucine-lysine-cysteine (IKC) extension at the NH2-terminus, which was derived from the COOH-terminal end of the reported signal peptide. Large variations in the abundance of the IKC isoforms between truncated SP-As suggested that the amino acid sequences located downstream from the signal peptide modulated alternate-site cleavage by signal peptidase. Elution of the newly identified cysteine in the position of DiPTH-Cys indicated participation in disulfide linkage, which was interchain based on the direct correlation between prevalence of the IKC variant and the extent of dimerization for each truncated protein. Sequencing of both native rat SP-A and human SP-A also revealed isoforms with disulfide-forming NH2-terminal extensions. The extended rat SP-A isoforms were enriched in the more fully glycosylated and multimeric SP-A species separated on SDS-PAGE gels. Thus, a novel post translational modification results in naturally occurring cysteinyl isoforms of rat SP-A, which are essential for multimer formation.
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PMID:Alternate amino terminal processing of surfactant protein A results in cysteinyl isoforms required for multimer formation. 918 99

Fractions of rib cartilage were obtained by homogenization and extracted with 4 M guanidinium chloride, and the washed residue was digested with purified collagenase. Differential centrifugation of the insoluble residue from this digestion yielded a non-collagenous fraction that earlier work had shown to contain microfibrils. This material contains a much higher concentration of epsilon(gamma-glutamyl)lysine than the ribs or any of the other cartilage fractions. This transglutaminase-derived crosslink may be a common component of extracellular matrix microfibrils.
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PMID:epsilon(gamma-Glutamyl)lysine crosslinks are concentrated in a non-collagenous microfibrillar fraction of cartilage. 919 78

To determine whether morphologic changes are accompanied by variations in the biochemical and antigenic properties of the cuticle of Onchocerca volvulus during development, we isolated and compared the 2-mercaptoethanol soluble cuticular proteins and the insoluble cuticlin from the predominant life-cycle stages occurring in man. SDS-PAGE analysis, before and after digestion with collagenase from Achromobacter iophagus, revealed that the polypeptide composition of the 2-mercaptoethanol-solubilised extracts from adult males and nodular microfilariae are quite distinct and that these extracts contained predominantly collagen-like proteins. Demonstrated by immunoblotting with a hyper immune patient serum pool (n = 107), five strongly reactive antigens with apparent molecular weights of 126, 68, 43, 37 and 33 kDa were detected in the extracts from adult males, while at least eight prominent and several weakly reactive components were detected in the extracts from nodular microfilariae. The overall amino acid composition of the cuticular extracts from the various stages demonstrates that: (a) the cuticle of the adult male stage is rich in glycine, pyrrolidone amino acids, and acidic amino acids or their amides, (b) eggshells are particularly poor in proline but rich in serine residues (14.5%), (c) nodular microfilariae cuticular extracts are poor in proline but rich in valine (9.0%) and lysine (7.3%) and (d) hydroxyproline and hydroxylysine are present in the cuticle of adults but absent in the juvenile life-cycle stages (nodular microfilariae and eggs). This study firstly, indicates that the composition of the cuticle of O. volvulus may thus, be quite distinct from one parasite stage to another and secondly, that the maturation of the parasite in the human host may be accompanied by the extensive hydroxylation of prolyl residues and to a lesser extent of lysyl residues in the predominantly collagen-like cuticular proteins.
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PMID:Evidence for increased hydroxylation of pyrrolidone amino acid residues in the cuticle of mature Onchocerca volvulus. 919 61

The aim of this study was to examine the fascia transversalis (FT) from patients with direct and indirect hernia in an attempt to identify possible differences between each type of hernia. FT samples were obtained from 36 patients presenting inguinal hernia (23 indirect hernia and 13 direct hernia) who underwent surgery. We have analysed the ultrastructure of the fascia surrounding the hernial lesions, the proline and lysine hydroxylation in the tissue, the type I-type III collagen ratio and the presence of metalloproteinases. We have not detected ultrastructural differences in the collagen fibrils from FT in direct and indirect hernias. However, the interfibrillar matrix was more abundant in direct hernias, showing abundant electron-dense particles. No differences in proline hydroxylation were observed between each type of hernia. A small decrease in lysine hydroxylation was detected in patients with direct hernia. Enzyme-linked immunosorbent assays (ELISAs) showed no statistically significant differences in the type I-type III collagen absorbance ratios. Immunohistochemistry revealed no differences in the expression of matrix metalloproteinase-1. FT from patients presenting direct hernia showed a very strong staining vs. metalloproteinase-2 when compared with that observed in indirect hernia.
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PMID:Study of biochemical substrate and role of metalloproteinases in fascia transversalis from hernial processes. 922 32

The dermis of the sea cucumber Cucumaria frondosa is a mutable collagenous tissue composed of collagen fibrils, microfibrils, proteoglycans, and other soluble and insoluble components. A major constituent of the dermis is a network of 10-14 nm microfibrils which surrounds and penetrates bundles of collagen fibrils. These microfibrils, which are morphologically very similar to the fibrillin microfibrils of vertebrates, were found to be insoluble in protein denaturants, including chaotropic agents and ionic and nonionic detergents, regardless of the reduction of disulfide bonds. The microfibrils are covalently crosslinked by epsilon-(gamma-glutamyl)lysine at a concentration of 3.725 nmol/mg dry weight of purified insoluble material. The network is susceptible to proteolysis by trypsin, chymotrypsin, and pancreatic elastase, but not by bacterial collagenase. Amino acid compositional analysis of the network shows it to be composed of 25% ASX and GLX residues. Comparison with the proteins in the SwissProt database gives the network protein a high probability of being related to the mammalian protein fibrillin. The network is glycosylated: approximately 7% of the mass is constituted by neutral and amino sugars. The intact microfibrillar network cross-reacted with a well-characterized antiserum to mammalian fibrillin.
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PMID:Partial biochemical and immunologic characterization of fibrillin microfibrils from sea cucumber dermis. 951 89

This work describes the results of the controlled crosslinking of collagen matrices by glutaraldehyde based on a double protection strategy, glutaraldehyde acetals and lysine protonation due to the acidic conditions of acetal formation. Materials crosslinked by this approach were characterized by thermal stability comparable to those obtained by conventional procedures with mechanical properties expected for bioprosthesis manufacture and with a higher stability toward collagenase hydrolysis. The integrity of the microfibrillar structure was confirmed by optical and scanning electronic microscopy. The results indicate that the glutaraldehyde acetals procedure may be of potential use for the crosslinking of bovine pericardium used in the manufacture of bioprosthetic devices. Advantages may be related to the production of materials with homogeneous crosslinking distributions, associated with better definition in the nature of the chemical link that they introduce, due to a better distribution of glutaraldehyde within the tissue matrix before the crosslinking reaction is allowed to occur. As a result, materials with improved biological and mechanical properties are expected.
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PMID:The chemical protecting group concept applied in crosslinking of natural tissues with glutaraldehyde acetals. 952 81

The distribution of type I collagen, the major component of human dermis, was characterized by immunohistochemistry in skin lesions of chromoblastomycosis, a chronic cutaneous mycosis, before and after a specific antifungal treatment with terbinafine to study the changes induced in the lesions by the treatment. Newly synthesized type I collagen was studied with an antibody directed against the aminoterminal propeptide of the molecule (PINP), whereas mature, cross-linked type I collagen was detected with an antibody against the carboxyterminal telopeptide of type I collagen (ICTP). The isopeptide N epsilon gamma-glutamyl lysine (N epsilon gamma GL), synthesized by transglutaminase and able to cross-link several components of the extracellular matrix, has also been investigated with two monoclonal antibodies to determine if it is involved in the stabilisation of the fibrotic cutaneous lesions. The degradative process involved in the remodelling has also been assessed by immunohistochemistry with anti-metalloproteinase (MMP-1 and MMP-9) and anti-tissue inhibitor (TIMP-1) antibodies. All tissue macrophages stained for CD68 and MMP-9, but not for MMP-1, while the polymorphonuclear neutrophils had an elastase and a weak MMP-9 phenotype. The fibroblasts of fibrotic areas stained constantly for N epsilon gamma GL and PINP. The immunostaining of extracellular matrix for ICTP and N epsilon gamma GL, and the number of PINP-positive fibroblasts, decreased significantly after one year of antifungal treatment. Terbinafine treatment decreases the synthesis of type I collagen and leads to a partial reversal of the cutaneous fibrotic lesions, independently of the cure of the fungal infection.
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PMID:Immunohistochemical study of type I collagen turn-over and of matrix metalloproteinases in chromoblastomycosis before and after treatment by terbinafine. 989 50

Mutant K246A in the predicted helix 3 of the ligand-binding domain, as well as mutants L417S and E420Q in helix 12, which contains the core ligand-dependent transcriptional activation domain (AF-2), were generated to examine AF-2 activity of the vitamin D receptor (VDR). These mutations abolished vitamin D-dependent transactivation. In addition, VDR mediates a ligand-dependent repression of the response of the retinoic acid receptor beta2 promoter to retinoic acid, and the helix 3 and helix 12 mutants were unable to mediate transrepression. Furthermore, the VDR mutants, but not the native receptor, enhanced phorbol ester induction of the activator protein-1-containing collagenase promoter. The helix 3 and helix 12 mutations strikingly reduced the ability of VDR to interact with the coactivators steroid receptor coactivator-1, ACTR, and the CREB-binding protein. As a consequence, overexpression of steroid receptor coactivator-1 increased vitamin D-dependent transactivation by VDR but not by the K246A mutant. These results indicate that the lysine 246 participates, together with residues in helix 12, in the recruitment of coactivators and that AF-2 activity is involved both in ligand-dependent transactivation and in transrepression by VDR.
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PMID:Lysine 246 of the vitamin D receptor is crucial for ligand-dependent interaction with coactivators and transcriptional activity. 1022 18


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