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)

Chondronectin, the chondrocyte attachment factor, was purified from chicken serum and characterized as to its physical and chemical properties. From sedimentation equilibrium data it was found to have a native molecular weight of 175,800 +/- 800 and a subunit molecular weight of 55,540 +/- 800 in the presence of guanidinium chloride and cysteine, suggesting a trimeric structure linked by disulfide bonds. As visualized by electron microscopy after rotary shadowing, the protein appears compact and globular. The amino acid and carbohydrate compositions of chondronectin are distinct from fibronectin, the fibroblast attachment factor, and laminin, the epithelial cell attachment factor. The activity of chondronectin in promoting attachment of chondrocytes is stable to digestion by collagenase, elastase, and neuraminidase, but is destroyed by trypsin treatment. The data suggest that chondronectin is structurally and chemically distinct from fibronectin and laminin.
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PMID:Chondronectin: physical and chemical properties. 408 2

1. Experiments were made to determine whether the purified lysosomal proteinases, cathepsins B1 and D, degrade acid-soluble collagen in solution, reconstituted collagen fibrils, insoluble collagen or gelatin. 2. At acid pH values cathepsin B1 released (14)C-labelled peptides from collagen fibrils reconstituted at neutral pH from soluble collagen. The purified enzyme required activation by cysteine and EDTA and was inhibited by 4-chloromercuribenzoate, by the chloromethyl ketones derived from tosyl-lysine and acetyltetra-alanine and by human alpha(2)-macroglobulin. 3. Cathepsin B1 degraded collagen in solution, the pH optimum being pH4.5-5.0. The initial action was cleavage of the non-helical region containing the cross-link; this was seen as a decrease in viscosity with no change in optical rotation. The enzyme also attacked the helical region of collagen by a mechanism different from that of mammalian neutral collagenase. No discrete intermediate products of a specific size were observed in segment-long-spacing crystalloids (measured as native collagen molecules aligned with N-termini together along the long axis) or as separate peaks on gel filtration chromatography. This suggests that once an alpha-chain was attacked it was rapidly degraded to low-molecular-weight peptides. 4. Cathepsin B1 degraded insoluble collagen with a pH optimum below 4; this value is lower than that found for the soluble substrate, and a possible explanation is given. 5. The lysosomal carboxyl proteinase, cathepsin D, had no action on collagen or gelatin at pH3.0. Neither cathepsin B1 nor D cleaved Pz-Pro-Leu-Gly-Pro-d-Arg. 6. Cathepsin B1 activity was shown to be essential for the degradation of collagen by lysosomal extracts. 7. Cathepsin B1 may provide an alternative route for collagen breakdown in physiological and pathological situations.
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PMID:Cathepsin B1. A lysosomal enzyme that degrades native collagen. 420 88

This report suggests a mechanism for collagen degradation mediated by human granulocytic leukocytes. A specific collagenase, which is extractable from human granulocytes, has been partially purified by DEAE chromatography. This collagenolytic enzyme is operative at physiological pH and is inhibited by EDTA, cysteine, and reduced glutathione but not by human serum. The enzyme cleaves the collagen molecule into two specific products, without loss of helical conformation. Electron micrographs of segment long spacing aggregates indicate that the cleavage occurs one-quarter of the length from the carboxy terminal end of the molecule. Experiments with crude extracts from granulocytes suggest that the specific products of granulocyte collagenase activity are then degraded by other proteases present in the human granulocyte.
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PMID:Degradation of collagen by a human granulocyte collagenolytic system. 430 77

1. A latent collagenase, activated only by limited proteolysis, was found in culture media of mouse bone explants. It could be activated by trypsin or, less efficiently, by chymo-trypsin. Skin explants also released latent collagenase. 2. Bone collagenase attacks native collagen at about neutral pH when it is in solution, in reconstituted fibrils or in insoluble fibres, producing two fragments representing 75 and 25% of the molecule. It requires calcium and is inhibited by EDTA, cysteine or serum. 3. Latent collagenase is not activated by trypsin-activated collagenase but by a distinct unidentified thermolabile agent present in a latent trypsin-activatable state in the culture media, or by purified liver lysosomes between pH5.5 and pH7.4. Trypsin activation decreases the molecular weight of latent collagenase from 105000 to 84000 as determined by gel filtration. 5. The latency of collagenase is unlikely to be due to an enzyme-inhibitor complex. Although some culture media contain a collagenase inhibitor, its presence is not constant and its molecular weight (at least 120000) is not compatible with the decrease in molecular weight accompanying activation; also combinations of collagenase with inhibitor are not reactivated by trypsin. Moreover, the latency remains after gel filtration, or treatment by high dilution, exposure to pH values between 2.5 and 10, or high ionic strength, urea or detergent. 6. It is proposed that latent collagenase represents an inactive precursor of the enzyme, a ;procollagenase', and that the extracellular activity of collagenase is controlled by another protease that activates procollagenase by a limited proteolysis of its molecule.
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PMID:The release of collagenase as an inactive proenzyme by bone explants in culture. 434 9

1. Explants of rabbit skin and synovium in tissue culture secreted a specific collagenase into their culture media. Primary cultures of fibroblast-like cells, which were obtained from these tissues and maintained in culture for up to 14 subculture passages, also secreted high activities of a specific collagenase into serum-free culture medium. Secretion of enzyme activity from the cell monolayer was at constant rate for over 100h and continued for up to 8 days in serum-free culture medium. The enzymic activity released was proportional to the number of cells in the monolayer. 2. The fibroblast collagenase was maximally active between pH7 and 8. At 24 degrees C the collagenase decreased the viscosity of collagen in solution by 60%. The collagen molecule was cleaved into three-quarters and one-quarter length fragments as demonstrated by electron microscopy of segment-long-spacing crystallites (measured as native collagen molecules aligned with N-termini together along the long axis), and by polyacrylamide-gel electrophoresis of the denatured products. The collagenase hydrolysed insoluble collagen, reconstituted collagen fibrils and gelatin, but had no effect on haemoglobin or Pz-Pro-Leu-Gly-Pro-d-Arg (where Pz=4-phenylazobenzyloxycarbonyl). 3. The fibroblast collagenase was partially purified by gel filtration and the molecular weight was estimated as 38000. The activity of the partially purified enzyme was stimulated by 4-chloromercuribenzoate, inhibited by EDTA, cysteine, 1,10-phenanthroline and serum, but was unaffected by di-isopropyl phosphorofluoridate, Tos-LysCH(2)Cl and pepstatin. 4. Long-term cell cultures originating from rabbit skin or synovium from rabbits with experimentally induced arthritis also secreted specific collagenase. Human fibroblasts released only very small amounts of collagenase.
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PMID:A specific collagenase from rabbit fibroblasts in monolayer culture. 436 13

A collagenase active against native collagen was found in culture fluids of bovine gingiva. The enzyme first appeared in the culture fluid after 1-2 days and could be harvested thereafter for at least 30 days. The collagenase attacked collagen fibrils and cleaved collagen in solution, resulting in reaction products 1/4 and 3/4 of the length of the original molecule. The enzyme was inhibited by serum, by EDTA and by cysteine. The molecular weight was estimated by gel filtration to be 63,000 daltons.
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PMID:Bovine gingival collagenase: demonstration and initial characterization. 437 18

1. An enzyme present in rat liver extracts degraded insoluble collagen maximally at pH3.5. Collagenolytic activity was more abundant in kidney, spleen and bone marrow and was also present in decreasing concentrations in ileum, lung, heart, skin and muscle. 2. The crude collagenolytic cathepsin was activated by cysteine and dithiothreitol, but not by 2-mercaptoethanol. Iodoacetamide, p-chloromercuribenzoate and 7-amino-1-chloro-3-l-tosylamidoheptan-2-one hydrochloride inhibited the enzyme. Zn(2+), Fe(3+) and Hg(2+) ions were strongly inhibitory, but Ca(2+), Co(2+), Mg(2+) and Fe(2+) ions had little or no effect. EDTA was an activator of the enzyme. Inhibitors of cathepsin B were found to enhance collagenolysis, but phenylpyruvic acid, a cathepsin D inhibitor, inhibited the enzyme. Di-isopropyl phosphorofluoridate had no effect. 3. Collagenolysis at pH3.5 and 28 degrees C was restricted to cleavage of the telopeptide region in insoluble collagen, and the material that was solubilized consisted mostly of alpha-chains. 4. The collagenolytic cathepsin was separated from cathepsins B2 and D by fractionation on Sephadex G-100 and a partial separation from cathepsin B1 was obtained by chromatography on DEAE-Sephadex. 5. The function of the collagenolytic cathepsin in the catabolism of collagen is discussed in relation to the action of the other lysosomal proteinases and the neutral collagenase.
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PMID:The nature of the collagenolytic cathepsin of rat liver and its distribution in other rat tissues. 465 Nov 35

Marked differences were observed in intermediate sulphur metabolism between non-pathogenic strains of Bacteroides melaninogenicus var melaninogenicus (CP-) and pathogenic Bacteroides melaninogenicus asaccharolyticus (CP+). The CP+ strains, which produced collagenase and protease and caused formation of abscesses when injected subcutaneously into groins of guinea pigs, produced copious amounts of volatile sulphur compounds (VSC) which consisted predominantly of CH3SH and (CH3S)2. Hydrogen sulphide occurred in considerably lesser amounts. CP+ cultures yielded 8-fold more total volatile S, 15-fold more CH3SH and 260-fold more (CH3S)2 during 24 h of incubation in trypticase-yeast extract medium. Whereas H2S accounted for 60 per cent of the total volatile S content of the head-space of CP- cultures, it represented only 8 per cent of the volatile S in CP + systems. Although the CP-organisms did not grow as well as CP +, the differences in concentration of VSC may be only partly related to the disparity in growth rates. When the VSC concentrations were calculated on the basis of equivalent optical density of 1.0, the CP + strains still produced over 3-fold more total volatile S, 6-fold more CH3SH and 100-fold more (CH3S)2. A similar allowance for growth rate suggests that CP-strains may possess a greater potential to produce H2S. Both groups metabolized S-containing amino acids and serine, resulting in appreciable increases in H2S production by CP-. However, the two groups appeared to metabolize the carbon moiety of cystine an cysteine by different pathways. The addition of glucose to the medium depressed total volatile S production by both CP+ and CP-strains, attributable mostly to lower H2S levels. Whereas the omission of yeast extract and charcoal treatment of trypticase did not adversely effect the activity of CP+, it further markedly reduced the capacity of CP-cultures to produce VSC. These results suggest that VSC analysis offers a convenient means of assessing strain differences and pathogenic potential of B. melaninogenicus.
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PMID:Characterization of volatile sulphur production by pathogenic and non-pathogenic strains of oral Bacteroides. 612 35

Oral administration of 2-mercapto-2-methylpropanoyl-L-cysteine (SA 96), a newly synthesized sulfhydryl compound, showed protective and curative effects on adjuvant-induced arthritis in rats similarly to those seen with D-penicillamine (D-PA). However, the effects of these compounds were not dose-dependent, and the maximum effects of SA96 were observed at 10 mg/kg/day. On the contrary, SA96 and D-PA had little effect on the various acute and subacute inflammatory responses induced in rat and mice. Formation of hemolytic plaque forming cells in the spleen of mice immunized with 5 X 10(8) sheep red blood cells was potentiated by the oral administration of both compounds. These stimulatory effects of SA96 and D-PA on the humoral immune responses were also not dose-dependent, and the maximum effects of SA96 were observed with 10 mg/kg/day, as in the case of adjuvant-induced arthritis in rats. In in vitro experiments, the inactivation of rheumatoid factor and the inhibition of collagenase and bone alkaline phosphatase activities were observed with both compounds, but these effects of SA96 were more potent than those of D-PA. As there is a similarity in the pharmacological profiles of SA96 and D-PA, SA96 may prove to be clinically effective for rheumatoid arthritis.
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PMID:[Pharmacological studies of new sulfhydryl compounds 2-mercapto-2-methylpropanoyl-L-cysteine (SA96). I. Evaluation of anti-rheumatic action (author's transl)]. 624 2

The collagenases (I, II and III) have been obtained in a highly purified state from fresh cultural medium of Clostridium histolyticum. The collagenases were similar in their properties to clostridiopeptidase A. The three enzymes differed in their molecular weights, isoelectric points and in some chemical properties. Collagenase II exhibited the most potent hydrolytic activity. Its collagenolytic activity was two-fold higher and the peptidase activity was twenty-fold higher as compared with that of collagenase I. All the three enzymes were inactive towards azocasein and were inhibited by EDTA and cysteine.
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PMID:[Isolation and properties of 3 Clostridium histolyticum collagenases]. 625 91


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