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)

To get a better understanding of the possible role of proteases in the pathogenesis of fungal keratitis, the extracellular proteases of a clinical isolate of Aspergillus flavus, from a severe case of keratitis, were identified and partially characterized. This strain, designated CU226/88, was grown with a variety of substrates as nitrogen sources, under conditions that would be expected to derepress the production of extracellular proteases. When grown on minimal medium with milk protein as a nitrogen source, the fungus appeared to produce primarily a metalloprotease, which has a zinc cofactor. When grown with insoluble collagen or elastin as a nitrogen source, a serine protease and cysteine protease, as well as the metalloprotease, are produced. Strain CU226/88 can grow with collagen, but not elastin, as the sole source of carbon as well as nitrogen. It is possible that the collagenase activity is a mediator of the severe corneal destruction caused by this isolate.
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PMID:Extracellular proteases of Aspergillus flavus. Fungal keratitis, proteases, and pathogenesis. 217 95

Live Haemonchus contortus developmental stages were radioiodinated and then subjected to a stepwise extraction procedure consisting of a buffer extract (with or without detergent) to solubilize putative surface-associated antigenic macromolecules, followed by a detergent/beta-mercaptoethanol (BME) extract to solubilize putative cuticle collagen proteins. A buffer-extracted iodinated 100-kDa protein was present in the free-living, infective L3(2M) stage. This labeled protein was released during in vitro exsheathment of L3(2M) and was not present in the ecdysed second molt (2M) cuticle. In addition to the 100-kDa protein, exsheathment fluid contained a 70-kDa labeled protein that was not extracted from iodinated L3(2M) with either detergent or BME. The data suggest that these proteins are components of the specialized ring portion of the 2M cuticle that is enzymatically ruptured during ecdysis. The L3(2M) and the exsheathed third-stage larvae (L3) contained 3 labeled, BME-extracted, collagenase-sensitive proteins of 108, 88 and 53 kDa. In contrast, four detergent-extracted, collagenase-insensitive, iodinated proteins (143, 81, 58 and 30 kDa) were present in adult H. contortus. The 143-kDa protein was both glycosylated and immunogenic. All 4 adult cuticle proteins were released from the cuticle surface into culture fluids. Furthermore, a cysteine protease was secreted by adults which apparently hydrolyzed the released 81-, 58- and 30-kDa surface proteins.
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PMID:Biochemical and immunochemical characterization of 125I-labeled cuticle components of Haemonchus contortus. 227 98

Hedgehog plasma was separated by gel filtration on Sephacryl S-200, the fractions resolved by electrophoresis and the electrophoretograms characterized for collagenase, papain and plasmin inhibiting activities with the high mol. wt substrate casein. The three inhibitors previously identified as alpha 2-, alpha 2-beta- and beta-macroglobulins were found to inhibit all three proteases. These were the only collagenase inhibitors found in plasma. Hedgehog alpha 2-chymotrypsin inhibitor and beta-protease inhibitor were both found to also inhibit papain. Three new inhibitors specific for papain (gamma-, alpha 2- and alpha 1-cysteine protease inhibitors) and one for plasmin (alpha 2-antiplasmin) were also found, bringing the number of protease inhibitors in hedgehog plasma to 14. Immunological cross-reactivity as studied by immunoelectrophoresis showed homology between hedgehog alpha 2-macroglobulin and rat murinoglobulin I and between hedgehog alpha 2-antithrombin and rat antithrombin III.
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PMID:Further studies of plasma protease inhibitors in the hedgehog, Erinaceus europaeus; collagenase, papain and plasmin inhibitors. 288 40

Cathepsin L is a lysosomal cysteine protease whose expression and secretion is induced by malignant transformation, growth factors, and tumor promoters. Many human tumors express high levels of cathepsin L, which is a broad spectrum protease with potent elastase and collagenase activities. Two published human cathepsin L cDNA sequences differ only in their 5'-untranslated regions. In this study, we demonstrate the concurrent expression of two distinct human cathepsin L mRNAs (hCATL-A and hCATL-B) in adenocarcinoma, hepatoma, and renal cancer cell lines. Cloning of the human cathepsin L gene by polymerase chain reaction amplification of genomic DNA and subsequent sequencing reveals that hCATL-A and hCATL-B mRNAs are encoded by a single gene. The 3' end of the first intron contains the 5' portion of hCATL-B and is contiguous to the second exon of the gene. These data suggest either the possibility of alternative splicing or the presence of a second promoter within the first intron of the hCATL gene. We mapped the hCATL gene to chromosome 9q21-22. Sequencing of both the mouse and human cathepsin L genes demonstrates almost complete conservation of exon and intron position, but significant divergence in intron structure, possibly reflecting differences in regulation of expression of the mouse and human cathepsin L genes.
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PMID:Cloning, genomic organization, and chromosomal localization of human cathepsin L. 841 12

Replacement of the single cysteine residue (C192) with serine in the Streptococcus pyogenes extracellular cysteine protease (SCP) prevented auto-catalytic processing of the 40-kDa zymogen to the 28-kDa mature form and eliminated proteolytic activity. SCP incubated with human endothelial cells induced a time- and concentration-dependent increase in a 66-kDa gelatinase/type IV collagenase in culture supernatants. Activation of this gelatinase/collagenase may contribute to endothelial cell damage, tissue destruction, and hemodynamic derangement observed in some patients with severe, invasive S. pyogenes infection.
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PMID:Structure-function and pathogenesis studies of Streptococcus pyogenes extracellular cysteine protease. 933 20

The purified metalloprotease and the partially purified cysteine protease from pathogenic Cryptobia salmositica were characterized. Using haemoglobin gel electrophoresis, we detected five enzymatic bands in crude parasite lysate; one protease (200 kDa) yielded a metalloprotease band and other four, cysteine protease bands (97, 70, 66 and 49 kDa). Both the metalloprotease and the cysteine protease had high levels of proteolytic activity against azocasein, haemoglobin and fibrinogen. The metalloprotease had high levels of activity against azocoll and gelatin but a low degree of activity against albumin. In contrast, the cysteine protease had extensive activity against albumin but low levels of activity against azocoll and gelatin. The metallo- and cysteine proteases had no activity against Pz-peptide, a specific substrate for bacterial collagenase. The optimal pH for the metalloprotease and the cysteine protease was 7.0 and 5.0, respectively. The metalloprotease was inhibited by metal-chelating agents and excess of zinc ions but was activated by calcium ions. The cysteine protease was inhibited by thiol-blocking agents. The natural antiprotease alpha2-macroglobulin, but not alpha1-protease inhibitor, inhibited the activity of both proteases from C. salmositica. The optimal in vitro temperature for the purified metalloprotease was 30 degrees C.
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PMID:Characterization of purified metallo- and cysteine proteases from the pathogenic haemoflagellate Cryptobia salmositica Katz 1951. 966 Jan 40

We determined the surface-associated proteolytic activity in three Entamoeba histolytica Schaudinn, 1903 strains (monoxenic HM1, axenic HM1, and HK9) of known virulence and its relationship with collagenase activity. Both activities were also determined in axenic HM1 amoebae trophozoites which were sensitive and resistant to complement-mediated lysis. Surface proteolytic activity was determined in glutaraldehyde-fixed E. histolytica trophozoites, which degraded the insoluble substrate, hide powder azure, and cleaved the human immunoglobulin G heavy chain in a time-dependent fashion, at neutral pH, in presence of 2-mercaptoethanol as cysteine protease activator. Surface proteolytic activity was strain dependent: monoxenic HM1 > axenic HM1 > axenic HK9. This activity correlated with collagenolytic activity (p < 0.05). Acquisition of resistance to complement-mediated lysis by axenic HM1 strain did not modify either surface proteases or collagenase expression. Our results suggest that this surface proteolytic activity could be used as an in vitro virulence marker for E. histolytica.
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PMID:Entamoeba histolytica: surface proteolytic activity and its relationship with in vitro virulence. 1055 49

Fusobacterium nucleatum subsp. nucleatum has been associated with a variety of oral and nonoral infections such as periodontitis, pericarditis, bone infections, and brain abscesses. Several studies have shown the role of plasmin, a plasma serine protease, in increasing the invasive capacity of microorganisms. In this study, we investigated the binding of human plasminogen to F. nucleatum subsp. nucleatum, and its subsequent activation into plasmin. Plasminogen-binding activity of bacterial cells was demonstrated by a solid-phase dot blot assay using an anti-plasminogen antibody. The binding activity was heat resistant and involved cell-surface lysine residues since it was abolished in the presence of the lysine analog epsilon-aminocaproic acid. Activation of plasminogen-coated bacteria occurred following incubation with either streptokinase, urokinase-type plasminogen activator (u-PA), or a Porphyromonas gingivalis culture supernatant. In the case of the P. gingivalis culture supernatant, a cysteine protease was likely involved in the activation. The plasmin activity generated on the cell surface of F. nucleatum subsp. nucleatum could be inhibited by aprotinin. Activation of plasminogen by u-PA was greatly enhanced when plasminogen was bound to bacteria rather than in a free soluble form. u-PA-activated plasminogen-coated F. nucleatum subsp. nucleatum was found to degrade fibronectin, as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Tissue inhibitor of metalloproteinase-1 was also degraded by the plasmin activity generated on the bacterial cells. This study suggests a possible role for plasminogen, which is present in affected periodontal sites, in promoting tissue destruction and invasion by nonproteolytic bacteria such as F. nucleatum subsp. nucleatum.
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PMID:Acquisition of plasmin activity by Fusobacterium nucleatum subsp. nucleatum and potential contribution to tissue destruction during periodontitis. 1056 61

Pycnodysostosis (Pycno) is an autosomal recessive osteosclerotic skeletal dysplasia that is caused by the markedly deficient activity of cathepsin K. This lysosomal cysteine protease has substantial collagenase activity, is present at high levels in osteoclasts, and is secreted into the subosteoclastic space where bone matrix is degraded. In vitro studies revealed that mutant cathepsin K proteins causing Pycno did not degrade type I collagen, the protein that constitutes 95% of organic bone matrix. To determine the in vivo effects of cathepsin K mutations on bone metabolism in general and osteoclast-mediated bone resorption specifically, several bone metabolism markers were assayed in serum and urine from seven Pycno patients. Two markers of bone synthesis, type I collagen carboxy-terminal propeptide and osteocalcin, were normal in all Pycno patients. Tartrate-resistent acid phosphatase, an osteoclast marker, was also normal in these patients. Two markers that detect type I collagen telopeptide cross-links from the N and C termini, NTX and CTX, respectively, were low in Pycno. A third marker which detects a more proximal portion of the C terminus of type I collagen in serum, ICTP, was elevated in Pycno, a seemingly paradoxical result. The finding of decreased osteoclast-mediated type I collagen degradation as well as the use of alternative collagen cleavage sites by other proteases, and the accumulation of larger C-terminal fragments containing the ICTP epitope, established a unique biochemical phenotype for Pycno.
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PMID:Determination of bone markers in pycnodysostosis: effects of cathepsin K deficiency on bone matrix degradation. 1057 90

Cathepsin K is the predominant cysteine protease in osteoclast-mediated bone remodeling, and the protease is thought to be involved in the pathogenesis of diseases with excessive bone and cartilage resorption. Osteoclastic matrix degradation occurs in the extracellular resorption lacuna and upon phagocytosis within the cell's lysosomal-endosomal compartment. Since glycosaminoglycans (GAGs) are abundant in extracellular matrixes of cartilage and growing bone, we have analyzed the effect of GAGs on the activity of bone and cartilage-resident cathepsins K and L and MMP-1. GAGs, in particular chondroitin sulfates, specifically and selectively increased the stability of cathepsin K but had no effect on cathepsin L and MMP-1. GAGs strongly enhanced the stability and, to a lesser extent, the catalytic activity of cathepsin K. To combine the activity and stability parameters, we defined a novel kinetic term, named cumulative activity (CA), which reflects the total substrate turnover during the life span of the enzyme. In the presence of chondroitin-4-sulfate (C-4S), the CA value increased 200-fold for cathepsin K but only 25-fold with chondroitin-6-sulfate (C-6S). C-4S dramatically increased the hydrolysis of soluble as well insoluble type I and II collagens, whereas the effects of C-6S and hyaluronic acid were less pronounced. C-4S acts in a concentration-dependent manner but reaches saturation at approximately 0.1%, a concentration similar to that found in the synovial fluid of arthritis patients. C-4S increased the cathepsin K-mediated release of hydroxyproline from insoluble type I collagen 10-fold but had only a less than 2-fold enhancing effect on the hydrolysis of intact cartilage. The relatively small increase in the hydrolysis of cartilage by C-4S was attributed to the endogenous chondroitin sulfate content present in the cartilage. Although C-4S increased the pH stability at neutral pH, a significant increase in the collagenolytic activity of cathepsin K at this pH was not observed, thus suggesting that the unique collagenolytic activity of cathepsin K at acidic pH is mechanistically determined and not by the enzyme's instability at neutral pH. The selective and significant stabilization and activation of cathepsin K activity by C-4S may provide a rationale for a novel mechanism to regulate the enzyme's activity during bone growth and aging, two processes known for significant changes in the GAG content.
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PMID:Collagenolytic activity of cathepsin K is specifically modulated by cartilage-resident chondroitin sulfates. 1064 77


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