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)

Extracellular matrix vesicles from bone and epiphyseal cartilage of femur and tibia of rats were isolated by collagenase digestion (crude vesicles) and further purified by sucrose gradient centrifugation. Fractions containing cells and membranes were also isolated from the two tissues. The alkaline and acid phosphatase and ATPase activities, as well as protein content of all fractions including crude and purified matrix vesicles, were assayed. The crude vesicles from both tissues demonstrated a high alkaline phosphatase specific activity (5-20 times higher than in the cell fraction). The total enzyme activities and protein content were significantly higher in all fractions from cartilage than those from bone. A major peak of alkaline phosphatase activity and protein content was obtained following the sucrose gradient centrifugation. The position of this peak was similar for both tissues. The specific activity of alkaline phosphatase of purified matrix vesicles was significantly higher in bone than in cartilage. The phosphatase activities from cartilage and bone showed a similar pH dependence and a similar response to metal ions. Of the metal ions tested (Na+, Mg2+, Zn2+, and Ca2+) only Zn2+ (at 5 mM concentration) inhibited significantly the alkaline phosphatase activity of purified matrix vesicles. The electrophoretic profile of purified matrix vesicles showed eight major protein bands common for both tissues. In addition, cartilage vesicles appeared to possess two peptides not found in bone.
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PMID:Biochemical characterization of matrix vesicles from bone and cartilage. 623 53

The effect of zinc deficiency on bone collagenase activity and collagen turnover was studied in the chick. Zinc deficiency symptoms, evident after 8 days on the low zinc diet, included tibia deformities and decreased alkaline phosphatase. Bone collagen metabolism was markedly altered, with a significant reduction in collagen synthesis and turnover. Half-turnover time for tibia collagen was 13 days in the control and 35 days in the zinc-deficient chicks. Tibia collagenase activity was reduced by 40-80% in the zinc-deficient as compared to the control chicks. Heparin markedly increased collagenase activity in the zinc-deficient tibias elevating activity to control levels. But commercially available heparin was found high in zinc content which may explain this effect entirely. These data show that zinc deficiency decreases bone collagen turnover and probably accounts for the leg deformities seen in zinc-deficient chicks.
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PMID:Effect of zinc deficiency on bone collagenase and collagen turnover. 625 4

Latent pig synovial collagenase (EC 3.4.24.7) can be activated by a variety of different treatments to give an active enzyme form of lower molecular weight which rapidly degrades collagen. Trypsin and plasmin effectively activated the latent collagenase whilst elastase and cathepsin G degraded most of the latent enzyme before it was activated. A number of mercurials were compared and maximum activation was achieved using 4-aminophenylmercuric acetate and phenylmercuric chloride. The latent collagenase bound to a mercurial-Sepharose column and was eluted in the active form with NaCl. The latent collagenase also activated spontaneously and the conditions which encouraged and prevented this activation were studied. High NaCl concentration, diisopropylphosphofluoridate, soybean trypsin inhibitor, low Zn2+ concentration and high and low pH all prevented the spontaneous activation of latent pig synovial collagenase.
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PMID:The activation of latent pig synovial collagenase. 626 Feb

A peptidase activity capable of excising in a single fragment the N-terminal extension of the precursor of collagen type III (p-N-collagen type III) was observed in calf tendon fibroblast culture medium. A new procedure was developed for detecting this peptidase (p-N-collagen type III peptidase). It is based on the use of 14C-labelled p-N-collagen type III obtained by carboxymethylation of the half-cystine residues with iodo-[14C]acetamide. The released labelled N-terminal extension is soluble in 27% (v/v) ethanol, whereas the uncleaved substrate and the collagen are precipitated under these conditions. The endopeptidase nature of p-N-collagen type III peptidase is supported by the similarity in molecular weight of the product of cleavage of p-N-collagen III by the enzyme to those obtained by cleavage with bacterial collagenase. An apparent Km of 0.3 X 10(-6)M was established. The pH optimum of p-N-collagen type III peptidase is similar to that of p-N-collagen type I peptidase, i.e. about 7.5. Both peptidases are inhibited by dithiothreitol and by Cu2+ and Zn2+, but not by other bivalent ions. p-N-collagen type III peptidase does not cleave p-N-collagen I or p-N-gelatin I. Partial purification of p-N-collagen type III peptidase from fibroblast culture medium was performed by sieve chromatography on Ultrogel AcA-34 to yield two peaks of activity, of mol.wts. 170000 and 100000. Part of the activity was retained on affinity chromatography on concanavalin A--Sepharose. Studied as a function of the age of the culture, p-N-collagen type III peptidase activity produced by tendon fibroblasts parallels that of p-N-collagen type I peptidase and collagen synthesis.
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PMID:Procollagen type III N-terminal endopeptidase in fibroblast culture. 626 32

1. Rabbit bones in tissue culture synthesize an inhibitor of collagenase during the first 4 days of culture. 2. The inhibitor was purified by a combination of gel filtration, concanavalin A--Sepharose chromatography, ion-exchange chromatography and zinc-chelate affinity chromatography. 3. The purified inhibitor migrated as a single band on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis and had a mol.wt. of 28000. 4. The inhibitor blocked the activity of the metalloproteinases collagenase, gelatinase, neutral proteinase III (proteoglycanase), human leucocyte collagenase and gelatinase, but not thermolysin or bacterial collagenase. The serine proteinases plasmin and trypsin were not inhibited. 5. The inhibitor interacted with purified rabbit bone collagenase with 1:1 stoichiometry. 6. The inhibitory activity was lost after incubation for 1 h at 90 degrees C, after treatment with trypsin (250 micrograms/ml) at 37 degrees C for 30 min and after reduction and alkylation.
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PMID:Purification of rabbit bone inhibitor of collagenase. 627 44

1. Inhibition of collagenase from rabbit bone cultures by the chelating agents 1,10-phenanthroline and EDTA is almost completely reversed by Zn2+; other metal cations are less effective in reversing the inhibition. Optimal restoration of activity is achieved at Zn2+ concentrations below that of the chelator, but excess of Zn2+ is inhibitory. 2. Prolonged incubation of collagenase with either chelator causes irreversible inactivation. This inactivation is prevented by Zn2+ at the same concentrations needed to reverse the primary inhibition. 3. Collagenase incorporates 65Zn by exchange when incubated with 1,10-phenanthroline and Zn2+ containing this radioactive isotope. The 65Zn2+ can be removed from its binding site in collagenase by 1,10-phenanthroline or EDTA. Irreversible inactivation of collagenase by chelators destroys its ability to incorporate 65Zn2+. 4. Latent collagenase, the inhibited form in which collagenase first appears in culture, behaves similarly to the active enzyme in 65Zn2+-exchange experiments, but is resistant to irreversible inactivation by chelators. 5. It is concluded that collagenase is a zinc metalloenzyme that forms an inactive and unstable apoenzyme on treatment with chelators. The bound inhibitor component of latent collagenase evidently stabilizes the apoenzyme.
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PMID:Zinc metalloenzyme properties of active and latent collagenase from rabbit bone. 627 47

Latent human PMN leucocyte collagenase (enzyme-inhibitor complex) was shown to require zinc for the property of being activatable by various disulfides [see Macartney, H.W. and Tschesche, H. (1980) FEBS Lett. 119, 327--332]. The active enzyme also requires zinc for activity, indicating a possible participation in the enzyme's reaction mechanism and/or stabilization of the active site. The zinc in the latent enzyme may be removed by dialysis against EDTA, or cysteine. This produces a zinc-free latent enzyme which cannot be activated by any of the disulfide-containing activators. Readdition of zinc to the EDTA-inhibited latent enzyme, at the same concentration as the EDTA, produces an activatable latent enzyme once again. However, excessive zinc concentrations (more than three times the concentration of EDTA) exhibited an inhibitory effect on the activation process. Thereafter the inhibitor cannot be removed by disulfides from the enzyme-inhibitor complex of the latent enzyme. The zinc in the latent enzyme may be replaced by other double-positive metal ions such as cobalt, manganese, magnesium and copper.
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PMID:The metal ion requirement for activation of latent collagenase from human polymorphonuclear leucocytes. 627 85

A collagenase from Empedobacter collagenolyticum was extracted from the culture medium of the bacteria. The complete purification of the enzyme was achieved by successive ammonium sulfate precipitation. Sephadex G 200 gel filtration and DEAE cellulose chromatography. This collagenase is active on insoluble collagen, and on the synthetic peptide Pz-Pro-Leu-Gly-Pro-D-Arg. Its optimum activity was at 30 degrees C and at pH 7.6. A strong inhibition was observed with chelating agents such as O-phenanthroline and EDTA. Among the cations tested to restore the activity, only Ca2+ has a measurable effect. Heavy metals, Pb, Hg, Cd, Cu, Fe, Co, strongly inhibit the enzyme activity. Zn2+ is also highly inhibitory; 10 microM ZnCl2 completely inhibits the collagenase. p CMB, iodoacetate have little effect on the collagenase. This new collagenase ressembles by most of its properties the already known bacterial collagenases.
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PMID:[Purification and study of some properties of a collagenase produced by Empedobacter collagenolyticum]. 627 75

Di- and tripeptides with sequences present in collagen that are known to occupy the S1' through S3' subsites at the active site of the collagenase from Clostridium histolyticum do not themselves inhibit this zinc protease. Thus glycylproline, glycylprolylalanine, and their C-terminal amides are not inhibitors. N alpha-Phosphorylglycylproline, N alpha-phosphorylglycyl-L-prolyl-L-alanine, and their C-terminal amides are weak inhibitors with IC50's (concentration causing half-maximal inhibition) of 4.6, 0.8, 3, and 1.5 mM, respectively. Extension of glycyl-L-prolyl-L-alanine to L-leucyl-glycyl-L-prolyl-L-alanine gives a tetrapeptide known to occupy the S1, S1', S2', and S3' subsites of collagenase when present in collagen but that still does not itself inhibit the enzyme. (Isoamylphosphonyl)glycyl-L-prolyl-L-alanine, a peptide containing a tetrahedral phosphorus atom at the position of the amide carbonyl carbon of the L-leucylglycyl amide bond of the parent tetrapeptide, inhibits collagenase with an IC50 of 16 microM, at least 1000-fold more potent than the parent peptide. Substitution of the two-carbon ethyl chain of alanine for the five-carbon isoamyl chain of leucine increases the IC50 to 46 microM. Substitution of the n-decyl chain for the isoamyl chain does not change the IC50. (Isoamylphosphonyl)glycyl-glycyl-L-proline contains a tripeptide that does not occupy the S1' through S3' subsites of collagenase when this peptide is present in collagen and thus has an IC50 of 4.4 mM. (Isoamylphosphonyl)glycyl-L-prolyl-L-alanine may be an analogue of the tetrahedral transition state for the hydrolysis of the natural collagen substrate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of collagenase from Clostridium histolyticum by phosphoric and phosphonic amides. 631 42

Several years ago the therapeutic possibilities for the treatment of inherited skin disorders were rather restricted; recently new possibilities have been developed and successfully applied. The author discusses the indications for a surgical procedure in basal cell nevus syndrome and the satisfying results revealed by dermabrasion in sebaceous adenoma of Pringle. The use of a low phenylalanine and tyrosine diet in case of palmoplantar keratosis with tyrosinemia is of theoretical as well as practical interest. However, a most striking therapeutic success is obtained by the treatment with drugs. The substitution of zinc in acrodermatitis enteropathica is very effective and not expensive! The positive effect of phenytoin in epidermolysis bullosa cicatricans is based on the partial inhibition of collagenase activity by this drug. Finally the author discusses the advantages of a treatment with retinoids in different hereditary keratinization disorders.
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PMID:[Therapeutic possibilities of hereditary diseases in dermatology]. 666 38


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