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:3.4.21.4 (trypsin)
42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The present study using immunologic methodology confirms previous observations from this laboratory of an absence of a protease component with arginine esterase activity in plasma of patients with cystic fibrosis. In this study, the pooled plasma from control individuals was activated and partially purified after adsorption on columns of soybean trypsin inhibitor conjugated to Sepharose 4B followed by elution with benzamidine. The fraction was further purified by isoelectrofocusing on polyacrylamide gels. Proteins around the pI range of 5.5 were eluted and utilized to prepare an antiserum. Immunoelectrophoresis of activated plasma samples from control subjects and patients with cystic fibrosis was performed utilizing the antiserum. In controls, four precipitin arcs with residual esterase activity were observed, whereas only three were seen in plasma from patients with cystic fibrosis. Double gel diffusion experiments using specific antisera ruled out the presence of trypsin, chymotrypsin, plasminogen, prothrombin, C1 esterase, alpha one-trypsin inhibitor, and inter-alpha-trypsin inhibitor in the concentrated benzamidine eluate. The antisera to alpha two-macroglobulin gave an immunoprecipitate which was readily stained for proteolytic activity. On immunoelectrophoresis, the alpha two-macroglobulin precipitin band corresponded to the band absent in plasma of patients with cystic fibrosis. In contrast, the alpha two-macroglobulin levels were similar in plasma of control subjects and patients with cystic fibrosis. Using the antiserum to the protein fractith proteolytic activity could be demonstrated in control plasma. One specific enzyme-active "rocket" was absent in plasma of patients with cystic fibrosis. In a double blind study of 15 control samples and 15 samples from patients with cystic fibrosis, a specific "rocket" was shown to be present in 13 control samples and absent in 14 cystic fibrosis samples. alpha two-Macroglobulin was determined by both an immunologic procedure and by its trypsin binding (trypsin protein esterase concentration). The ratio of the immunologic assay to the biologic activity assay was 90 for the normal plasma samples and only 65 for cystic fibrosis samples.
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PMID:Absence of an alpha two-macroglobulin-protease complex in cystic fibrosis. 6 Jul 35

p-Carbethoxyphenyl episol-guanidinocaproate and p-(p'-guanidinobenzoyloxy)-phenyl derivatives were prepared, and their inhibitory effects on trypsin, plasmin, plasma kallikrein, thrombin, C1r- and C1 esterase were examined. Among the various inhibitors tested, p-nitrophenyl p'-guanidinobenzoate, N,N-dimethylamino p-(p'-guanidinobenzoyloxy)-benzoyl glycolate and N,N-dimethylamino p-(p'-guanidinobenzoyloxy)-benzilcarbonyloxy glycolate were the most effective inhibitors of trypsin, plasmin, plasma kallikrien and thrombin, and they strongly inhibited the esterolytic activities of C1r- and C1 esterase.
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PMID:Synthetic inhibitors of trypsin, plasmin, kallikrein, thrombin, C1r-, and C1 esterase. 14 65

An inhibitor of procoagulant and fibrinolytic enzymes was derived from cabbage seeds by a procedure using acetone precipitation, ion-exchange chromatography, and gel filtration. The cabbage seed inhibitor was a 10-Kd monomeric protein with intrachain disulfide bonds. This preparation prevented clot formation in whole blood and blocked the ability of thrombin to induce clot formation in plasma and to induce platelet aggregation. A number of proteases were inhibited, as demonstrated by using purified enzymes in amidolytic assays. Tight-binding inhibition was observed for activated Stuart factor (factor Xa) and plasmin. Inhibition of thrombin and activated Hageman factor (factor XIIa) was observed with a molar excess of inhibitor. No inhibition was detected for activated plasma thromboplastin antecedent (factor XIa), plasma kallikrein, or C1 esterase. Reaction progress curves for trypsin indicated slow, tight-binding inhibition, with an apparent inhibition constant in the nanomolar range or less. The electrophoretic mobility of trypsin was altered by the inhibitor in nondenaturing polyacrylamide gel electrophoresis (PAGE) but not in sodium dodecyl sulfate (SDS)-PAGE, indicating noncovalent bonding. Only partial reversal of trypsin inhibition could be demonstrated by washing the inhibitor from enzyme immobilized on solid beads. A dot-blot technique with cabbage seed inhibitor was capable of detecting 10 ng nitrocellulose-bound trypsin. The dot-blot technique also appeared capable of detecting plasmin. These findings demonstrated the potential utility of this inhibitor as a probe for detection of tightly bound proteases. In summary, cabbage seed extracts contain an inhibitor with activity toward a broad range of proteases important to hemostasis. To our knowledge, this agent represents the first inhibitor isolated from a plant source that inhibits thrombin.
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PMID:Cabbage seed protease inhibitor: a slow, tight-binding inhibitor of trypsin with activity toward thrombin, activated Stuart factor (factor Xa), activated Hageman factor (factor XIIa), and plasmin. 213

Acute pancreatitis (AP) is believed to result from intraparenchymal activation of trypsin and other digestive enzymes within the pancreas followed by autodigestion of the gland. Gabexate mesilate (FOY), a synthetic guanidino acid ester exhibiting potent and versatile inhibitory actions on a number of proteinases (e.g., trypsin, kallikrein, C1-r, C1 esterase, plasmin, thrombin, phospholipase A2), was examined for its ability to protect the rat pancreas against development of AP induced by pharmacological doses of ceruletide (CRT). Rats were i.v. infused for 6 h with either CRT (5 micrograms/kg/h) or CRT + FOY (50 mg/kg/h). In FOY-treated rats the serum amylase and trypsinogen concentrations were reduced by 60 and 80%, respectively, compared to rats infused with CRT alone. Histologically, the extent of acinar cell vacuolization in the pancreas was significantly reduced and interstitial edema, although not assessed by quantitative morphometric techniques, appeared to be qualitatively lessened in the FOY-treated rats. The ability of FOY to inhibit significantly AP produced by supramaximal doses of CRT, coupled with its inhibitory properties on components of the coagulation and complement cascades, stress the importance of continued research on this compound as a potential therapeutic agent for treatment of AP and its systemic sequelae.
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PMID:Gabexate mesilate (FOY) protects against ceruletide-induced acute pancreatitis in the rat. 244 41

The effect of human skin mast cell tryptase on human plasma proenzymes (prothrombin, coagulation factor XII, complement C1s, protein C and plasminogen) was investigated. Tryptase had no effect on these proenzymes, when incubated with them at 37 degrees C for up to 90 min, as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and by the ability to hydrolyze specific peptide p-nitroanilide substrates. After prolonged treatment with tryptase, proenzymes could be fully activated with their specific activators. The results indicate that tryptase neither activates these plasma proenzymes nor inactivates the corresponding active enzymes. As a positive control, the tryptase preparation was also incubated with human fibrinogen and rat thymus histones. Prolonged treatment with tryptase increased the thrombin-induced clotting time of fibrinogen. Tryptase also efficiently hydrolyzed histone H1 from rat thymus. Histones H3/H2B and H2A were hydrolyzed less efficiently than H1, and no hydrolysis of histone H4 by tryptase was detected under the experimental conditions.
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PMID:Effect of human mast cell tryptase on human plasma proenzymes. 253 Jan 78

The domain organization of the zymogen subunits of the first component of human complement C1s, C1r2 and the complex C1s-C1r2-C1s was studied by electron microscopy. In the absence of Ca2+, monomeric C1s was visualized as a dumb-bell-shaped molecule consisting of two globular domains (center-to-center distance 11 nm) connected by a rod. One of the globular domains is assigned to the light chain (B-chain) of the activated molecule, which is homologous to trypsin and other serine proteases. The second globular domain and the rod are assigned to the heavy chain (A-chain) of CIs. The subunit C1r is a stable dimer in the presence or absence of Ca2+. This dimer C1r2 was visualized as composed of two dumb-bells of dimensions similar to those observed for C1s. These are connected near the junctions between the rod and one of the globular domains. This leads to the structure of an asymmetrical X with two inner closely spaced globules (center-to-center distance 7 nm) and two outer globules at a larger distance (14 nm). By comparison with fragment C1rII2, in which part of the A-chain is removed, the inner globular domains were assigned to the catalytic B-chains. This characteristic structure of C1r2 is readily recognized in the central portion of the thread-like 54 nm long C1s-C1r2-C1s complex formed in the presence of Ca2+. By affinity-labeling of C1s with biotin and visualization of avidin-ferritin conjugates in the reconstituted complex, it was demonstrated that C1s forms the outer portion of the complex. A detailed model of C1s-C1r2-C1s is proposed, according to which two C1s monomers bind to the outer globes of C1r2 by contacts between their heavy chains and those of C1r. According to this model the catalytic domains of C1r are located in the center and those of C1s at the very tips of the C1s-C1r2-C1s complex. On the basis of the structure of C1s-C1r2-C1s, we derived a detailed model of the C1 complex (composed of C1q and the tetrameric complex) and we discuss this model with a view to finding a possible activation mechanism of C1.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Functional model of subcomponent C1 of human complement. 302 30

FUT-175 (6 amidino-2-naphthyl-4-guanidino benzoate-dimethanesulfonate), a new synthetic protease inhibitor, inhibits the enzyme activities of various proteases, such as Clr, C1 esterase, thrombin, kallikrein, plasmin and trypsin. FUT-175 strongly inhibited complement-medicated hemolysis via the classical and alternative pathways. The effects of FUT-175 on various immunological reactions in vivo were studied. The minimal effective dose of FUT-175 in systemic Forssman shock in guinea pigs was 6.25 mg/kg i.p. and 25 mg/kg p.o. In passive Arthus reactions in rats, the effective dose was 25 mg/kg i.p. and 250 mg/kg p.o. FUT-175 also inhibited other immunological reactions, such as passive cutaneous anaphylaxis and delayed hypersensitivity. Furthermore, at a dose of 25 mg/kg i.p. it strongly protected mice from death in endotoxin shock.
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PMID:Inhibition of various immunological reactions in vivo by a new synthetic complement inhibitor. 621 61

p-Guanidinobenzoate derivates were prepared and their inhibitory effects on trypsin, plasmin, pancreatic kallikrein, plasma kallikrein, thrombin, C1r and C1 esterase were examined. Among the various inhibitors tested, 6'-amidino-2-naphthyl-4-guanidinobenzoate dihydrochloride, 4-(beta-amidinoethenyl)phenyl-4-guanidinobenzoate dimethanesulfonate and 4-amidino-2-benzoylphenyl-4-guanidinobenzoate dimethanesulfonate were the most effective inhibitors of trypsin, plasmin, pancreatic kallikrein. plasma kallikrein and thrombin and they strongly inhibited the esterolytic activities of C1r and C1 esterase, and then strongly inhibited complement-mediated hemolysis.
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PMID:New synthetic inhibitors of C1r, C1 esterase, thrombin, plasmin, kallikrein and trypsin. 627 Dec 24

The formation of EAC 4b2a is a two step reaction: first, the temperature- and time-independent binding of C2 to EAC4b2a resulting in EAC4b2 , secondly, the enzymatically triggered conversion of EAC4b2 to EAC4b2a . In the classical cascade of complement activation, the generation of C3 convertase activity is triggered by the C1 esterase, C1-s, which is part of C-1. Evidence is presented that the enzymes trypsin, chymotrypsin, plasmin, and pronase are also able to activate EAC4b2 to EAC4b2a . Kinetic studies showed that the formation of C3 convertase by these enzymes was dependent on concentration, temperature, and time. The optimal conditions were found as follows: trypsin, 2 micrograms/ml (final conc.) for 8 min at 23 degrees C; chymotrypsin 165 micrograms/ml for 18 min at 23 degrees C; plasmin 0.8 units/ml for 15 min at 23 degrees C; pronase 1.25 microgram/ml for 15 min at 23 degrees C. Even under optimal (tmax) conditions the number of generated EAC4b2a differed from enzyme to enzyme: trypsin (= 100%), pronase (58.3%), chymotrypsin (47.9%), and plasmin (12.9%). The enzymes were also able to generate C3 convertase activity from C2 which was adsorbed to EAC1i4b , a C1 inactivator treated and therefore hemolytically inactive intermediate ( EAC1i4b2 ). These findings underline the biological importance of C1 esterase replacing enzymes.
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PMID:Generation of the classical pathway C3 convertase (EAC4b2a) by proteolytic enzymes. 637 57

A cDNA of rat C6 cells was cloned, which was considered to be involved in glial cell differentiation induced by dibutyryl cyclic AMP and theophylline. The cDNA fragment of the gene, termed r-gsp, was originally isolated by mRNA fingerprinting using arbitrarily primed polymerase chain reaction, and was homologous to complement C1s precursors of hamster and human. It encodes a protein of 694 amino acids containing a potential signal peptide, an epidermal growth factor-like domain surrounded by two complement C1r/C1s-related repeats, and a putative trypsin-type serine protease domain. Since the hamster and human C1s, and a protein encoded by r-gsp shared high similarity in primary structure, the r-gsp gene could encode a C1s counterpart of the rat. Messenger RNA expression of this gene was markedly increased during cyclic AMP-induced glial cell differentiation. Its expression profile was well correlated with those of glial fibrillary acidic protein (GFAP) and S100B, which are known as glial differentiation markers. It was, moreover, observed that the r-gsp expression in brain increased considerably after birth, like those of S100B and GFAP. The results presented here suggest that the rat C1s gene would be also implicated in glial differentiation besides the complement cascade.
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PMID:Molecular cloning of a cDNA encoding a serine protease homologous to complement C1s precursor from rat C6 glial cells and its expression during glial differentiation. 952 31


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