Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.25.1 (proteasome)
 28,817 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Aspergillus fumigatus secreted an inducible alkaline protease (AlPase) when cultivated in the presence of collagen (200 micrograms/ml) as sole nitrogen and carbon source. Proteolytic activity was maximum at pH 9.0 with azocollagen as substrate. The enzyme, which was the major protein found in the supernate of a liquid culture, was purified by ammonium sulphate precipitation and gel filtration. The Mr was determined to be 33 Kda by gel filtration and sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The isoelectric point was estimated to be pH 8.2. Divalent cations strongly inhibited enzyme activity, whereas non-ionic detergents and reducing agents had no effect. A. fumigatus AlPase was totally inhibited by phenylmethanesulphonyl fluoride, antipain, chymostatin and alpha-2-macroglobulin. A. fumigatus AlPase is closely related to the A. oryzae AlPase, a serine protease of the subtilisin family, as attested by the antigen pattern seen by immunoblotting. The high collagenic activity and the ability of A. fumigatus AlPase to digest elastin could play a role in the invasion of the tissues by the fungus.
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PMID:Isolation and characterisation of an extracellular alkaline protease of Aspergillus fumigatus. 207 76

A glycoprotein of apparent molecular weight 58,000 (unreduced)/68,000 (in its reduced form) (gp 58/68), which is one of the fibronectin/collagen receptors of Trypanosoma cruzi, was purified to homogeneity from the trypomastigote forms of the Tehuantepec and Y strains of the parasite. Purified gp 58/68 inhibited formation of cell-bound and fluid-phase alternative pathway C3 convertase in a dose-dependent fashion, as assessed using purified human complement components. Gp 58/68 differed from the human regulatory proteins H, DAF, MCP and CR1 and from previously reported regulatory proteins on the parasite membrane in that it was unable to enhance decay-dissociation of preformed alternative pathway C3 convertase sites, did not serve as a co-factor for I-mediated cleavage of C3b and had no inhibitory activity on the classical pathway convertases. The inhibitory effect of gp 58/68 was most likely dependent on an interaction of the protein with factor B rather than with C3b. Gp 58/68 provides trypomastigotes with an additional potential mechanism for escaping complement lysis by the human alternative pathway.
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PMID:gp 58/68, a parasite component that contributes to the escape of the trypomastigote form of T. cruzi from damage by the human alternative complement pathway. 297 33

The activities of prolyl 4-hydroxylase (PH) and galactosylhydroxylysyl glucosyltransferase (GGT), both enzymes of collagen biosynthesis, were measured in the gastrocnemius, soleus, and tibialis anterior muscles of rats after bilateral cast-immobilization of the muscles in lengthened and shortened positions for one and three weeks. The activities of muscular proteolytic and hydrolytic enzymes cathepsin D (CD), beta-glucuronidase (beta-GU), alkaline protease (AP), and the rate of acid autolysis (AA) were also studied. The biochemical results were compared to the morphologic changes by light microscopy. Compared to the results for a control group, there was a decrease of 37% and 53% in the specific PH activity of shortened gastrocnemius and soleus, respectively, after three weeks of immobilization. The corresponding decrease in GGT of the shortened gastrocnemius was 47%. At the same time, PH and GGT in the lengthened plantarflexors were at the control level. The proteolytic activities of the shortened plantarflexors were generally higher (CD by approximately 30%, beta-GU of gastrocnemius by 81%, AP of soleus by 63%, AA of gastrocnemius by 34%, and AA of soleus by 56%) than those of the lengthened ones. Light microscopy of the shortened muscles showed numerous atrophic fibers, but no pronounced inflammatory response in the disused muscle tissue. The results suggest that increased proteolysis and wasting of muscle tissue during cast-immobilization is associated with adaptive responses in the metabolism of the muscular collagen network.
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PMID:Collagen synthesis and proteolytic activities in rat skeletal muscles: effect of cast-immobilization in the lengthened and shortened positions. 305 21

Purified Pseudomonas aeruginosa elastase cleaved human type III and IV collagens with the formation of specific cleavage products. Furthermore, type I collagen appeared to be slowly cleaved by both P. aeruginosa elastase and alkaline protease. These cleavage fragments from type III and IV collagens were separated from the intact collagen chains by SDS polyacrylamide gradient gel electrophoresis run under reducing conditions, and they were detected by their characteristic Coomassie blue staining pattern. The results of these studies suggest that the pathogenesis of tissue invasion and hemorrhagic tissue necrosis observed in P. aeruginosa infections may be related to the degradation of these collagen types by bacterial extracellular proteases.
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PMID:Specific cleavage of human type III and IV collagens by Pseudomonas aeruginosa elastase. 307 27

The activities of four lysosomal and two nonlysosomal hydrolases were studied in skeletal muscle biopsy samples from patients with neuromuscular diseases and from controls. beta-Glucosaminidase activity was increased in polymyositis. beta-Glucuronidase and alkaline protease activities were elevated in muscular dystrophy in adults, whereas cathepsin D activity was increased in amyotrophic lateral sclerosis. There were significant correlations between the activities of lysosomal and nonlysosomal hydrolases. The activity of beta-glucuronidase, beta-glucosaminidase, alkaline protease, and dipeptidyl aminopeptidase IV showed a positive correlation with the severity of muscular atrophy. The activities of these hydrolases and the activity of dipeptidyl aminopeptidase I correlated positively with the activities of muscular galactosylhydroxylysyl glucosyltransferase and with the serum concentration of type III procollagen aminoterminal propeptide. The results suggest that in neuromuscular diseases the lysosomal and nonlysosomal pathways for muscle degradation are affected concomitantly with collagen biosynthesis.
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PMID:Lysosomal and nonlysosomal hydrolases of skeletal muscle in neuromuscular diseases. 635 16

A membrane-associated receptor for the C1q subcomponent of complement is widely distributed among different cell types. While a number of possible physiological functions of the C1q receptor (C1qR) on different cell types have been described, the way in which C1qR regulates complement activity remains unclear. This report describes the mechanism by which C1qR regulates activation of the first component of complement, C1. Using purified components of complement, we were able to show that membrane-associated C1qR as well as detergent-solubilized C1qR, purified from polymorphonuclear leukocytes, human umbilical vein endothelial cells or an endothelial cell line, EA.hy 926, are able to inhibit complement-mediated lysis of C1q-sensitized erythrocytes. Using hemolytic assays, we were able to demonstrate that C1qR prevents the association of C1q with C1r and C1s to form macromolecular C1. In addition, incubation of C1qR with the collagen-like stalks, but not with the globular heads of C1q, inhibits the effect of C1qR. This demonstrates that C1qR exerts its complement inhibitory effect by binding to the collagen-like stalk of C1q. No complement regulatory effect of C1qR was observed on preformed macromolecular C1. These data suggest that besides such-well-known complement regulatory molecules as CD55 (DAF), CD46 (MCP), CD35 (CR1) and CD59 (HRF), C1qR too is able to regulate complement activity.
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PMID:Regulation of the function of the first component of complement by human C1q receptor. 766 83

Aspergillus fumigatus secretes a serine alkaline protease (ALP) and a metalloprotease (MEP) when the fungus is cultivated in the presence of collagen as sole nitrogen and carbon source. The gene encoding ALP was isolated and characterized previously. We report here the cloning and the sequencing of the gene encoding MEP. Genomic and cDNA clones were isolated from A. fumigatus libraries using synthetic oligonucleotides as probes. Stretches of the deduced amino acid sequence were found to be in agreement with the N-terminal amino acid sequence of MEP and with internal peptide sequences. The amino acid sequence of the enzyme contains a putative active-site sequence HEYTH homologous to the active site of other bacterial and eukaryotic zinc metalloproteases. Sequence analysis reveals that MEP has a pre-proregion consisting of 245 amino acid residues preceding the 388 amino acid residues of the mature region (molecular mass of 42 kDa). An alp mep mutant, deficient in proteolytic activity at neutral pH in vitro, was constructed and tested for pathogenicity in a murine model. No difference in pathogenicity was observed between the wild-type strain and the alp mep double mutant, suggesting that ALP and MEP are not essential for the invasion of the lung tissues by A. fumigatus.
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PMID:Cloning and disruption of the gene encoding an extracellular metalloprotease of Aspergillus fumigatus. 771 53

An extracellular proteasome-like (EP) structure has been isolated from serum-free media conditioned by C6 astrocytoma cells. EP has a native molecular mass of 1000 kDa and is composed of three subunits, two isoelectric variants at 70 kDa and one at 65 kDa. The extracellular proteasome degraded collagen IV, alpha-casein, beta-insulin, and certain synthetic peptide substrates. A 68-kDa type IV collagenase, identified as the activated form of gelatinase A, was also isolated from this medium. The type IV collagenase activity of the proteasome was sensitive to serine protease inhibitors, while the 68-kDa collagenase IV represented the matrix metalloprotease gelatinase A. The general protease activity of the proteasome was sensitive to metalloprotease inhibitors. Western blot analysis indicates a sequence relationship between the 68-kDa type IV collagenase and either one or both of the 70-kDa isoelectric variants of the proteasome; however, the two enzymes appear to be distinct functionally. Comparison with known proteasomes indicates that EP represents a novel proteasome. The complexity of degradative enzymes in the extracellular microenvironment implies that complete inhibition of tumor growth requires at least a combination of serine and metalloprotease inhibitors.
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PMID:An extracellular proteasome-like structure from C6 astrocytoma cells with serine collagenase IV activity and metallo-dependent activity on alpha-casein and beta-insulin. 787 29

Strains from several species of Aspergillus were grown in the presence of soluble collagen, and the major secreted proteins present in the culture fluid were examined for proteolytic activity. The possibility of relatedness among the alkaline proteases secreted by Aspergillus was studied by probing extracts from the various species with polyclonal antisera raised to the isolated alkaline proteases of A. fumigatus and A. oryzae. The pathogenic species A. flavus, A. terreus and A. nidulans hydrolyse collagen and were found to secrete an alkaline protease related to that of Aspergillus fumigatus. In contrast, A. niger and non-pathogenic species such A. glaucus, A. versicolor and A. clavatus were unable to degrade collagen in vitro. These findings suggest a possible pathogenic role for the secreted alkaline proteases of Aspergillus species.
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PMID:A study of the alkaline proteases secreted by different Aspergillus species. 793 65

The Aspergillus cell wall contains most of the antigens secreted by the fungus during its active in vitro or in vivo growth. These antigens, which bind to the IgE and IgG of allergic and aspergilloma patients or are secreted in the biological fluids of patients with invasive aspergillosis, are of primary importance in the diagnosis of aspergillosis. Located at the interface between host and pathogen cells, the fungal cell wall plays a major role during fungal invasion. It contains several surface receptors involved in adhesion of the fungus to host proteins and cells. Some of the wall antigens are also directly involved in the colonization of the host tissues by the fungus. Very few of these putative virulence factors have been purified until now. A 33-kDa alkaline protease of the subtilisin family can hydrolyze several extracellular matrix proteins such as collagen, fibrinogen, elastin. However, gene disruption experiments have shown that protease-deficient mutants are still able to infect mice. An 18-kDa antigen, which has been detected in the urine of patients with invasive aspergillosis, is present in vivo in the lung of mice infected with A. fumigatus. It has a ribonuclease activity that cleaves a single phosphodiester bond in a highly conserved region of the ribosomal RNA. Its role in the virulence of A. fumigatus has not been demonstrated until now. Biochemical and molecular characterization of the wall antigenic aggressins should be pursued.
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PMID:Cell wall antigens in Aspergillus fumigatus. 829 77


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