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)

Serine proteases are one of the biologically most important and widely distributed families of enzymes. Isolation of serine protease genes from organisms of widely diverged phylogenetic groups would provide a basis for studying their biological function, the relationship between structure and function, and the molecular evolution of these enzymes. Serine proteases for which little structural information is known are those that are important in the pathogenesis of parasitic nematode and protozoan diseases. Identification and isolation of protease genes from these organisms is a critical first step in understanding their function for the parasite and possibly suggesting innovative approaches to arresting parasitic diseases. Serine protease gene fragments were isolated from genomic DNA of the parasitic nematode Anisakis simplex by using degenerate oligonucleotide primers and the polymerase chain reaction. Primers were designed based upon the consensus sequence of amino acids flanking the active site serine and histidine residues of eukaryotic serine proteases. Four serine protease gene fragments from this parasite were sequenced and one is 67% identical to the rat trypsin II gene. Alignment of these two genes revealed that the intron-exon junctions are conserved between nematode and rat suggesting that this Anisakis serine protease is structurally and functionally similar to rat trypsin. The generality of this approach to identify serine protease genes from genomic DNA of two very divergent species, a parasitic protozoan and a mammal, was also confirmed. Genes for other enzymes or any protein with conserved structural motifs can be identified and isolated using this technology. Using a similar strategy, a cathepsin B-like cysteine (thiol) protease gene fragment was isolated from Caenorhabditis elegans DNA.
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PMID:Serine proteases from nematode and protozoan parasites: isolation of sequence homologs using generic molecular probes. 266 85

Characterization of the proteases was performed in the crude mite extract fractionated by Sephacryl S-200 gel filtration. Three peaks of protease activities were detected in the fractions. From the results of substrate specificity and susceptibility to the inhibitors, PK.1 protease (about 60 kD) is suggested to be a trypsin-like protease of mites. From the results of susceptibility to various agents, PK.2 (about 30 kD) and PK.3 (about 20 kD) proteases may be cysteine proteases, e.g., papain and cathepsin B. PK.3 protease existed in the precipitate of 60% ammonium sulfate fractionation. The data in the present study suggest the possibility that Dermatophagoides farinae I allergen might be a cysteine protease probably derived from the gastrointestinal tract of the house dust mite.
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PMID:Characterization of the proteases in the crude mite extract. 267 67

Malignant cells have the ability to invade and metastasize in great part because they secrete proteolytic enzymes. In order to investigate if the abnormal proteinase/antiproteinase balance of cancer bearing patients changes when the malignant tumor is destroyed, we studied 50 patients with invasive carcinoma of the cervix and 33 healthy women as a control group. Patients with cancer were treated with radiation according to the protocols of our hospital. The following serum determinations were performed: plasminogen activators (PA), cathepsin B (CB), antiproteinase alpha-1-antitrypsin (A1AT), trypsin inhibitory capacity (TIC) and antiproteolitic activity ratio (AAR), all of them before and after treatment. Serum proteolytic activity was elevated manyfold in all patients with invasive tumor as well A1AT. The antiproteolytic activity however, was significantly reduced to about 50% of its normal value in the same group of patients. In patients with good response to radiotherapy (tumor necrosis) a great reduction of proteinase activity as well as a recovery to normal of the AAR was observed. Contrary, in those with a poor response after radiation, proteolytic activity remained elevated and AAR diminished. It is concluded that serum PA, CB, A1AT and AAR values can be precise indicators of the presence of malignancy. These tests might be also of help for improving follow-up studies and for better prognostic estimates.
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PMID:[Protease-antiprotease balance in patients with invasive carcinoma of the cervix and uterus before and after radiotherapy]. 278 98

A unique calcium-dependent endopeptidase specifically cleaving on the carboxyl side of paired basic residues was partially purified from Golgi membrane fractions of rat liver. The enzyme, with optimal pH at around 6.0, hydrolyzes synthetic peptides corresponding to the amino-terminal sequences of proalbumin and proparathyroid hormone at the carboxyl sides of paired basic residues (Arg-Arg and Lys-Arg), but peptides corresponding to the amino-terminal sequences of proalbumin variants, in which Arg-Arg at the site of cleavage is replaced by Arg-Gln or His-Arg, are not affected by the enzyme. From its strict substrate specificity and inhibitory spectrum, this enzyme appears to be a novel endopeptidase distinct from trypsin and cathepsin B and may be physiologically involved in proprotein processing.
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PMID:A unique membrane-bound, calcium-dependent endopeptidase with specificity toward paired basic residues in rat liver Golgi fractions. 281 87

Cathepsins B and L were purified from human kidney. SDS/polyacrylamide-gel electrophoresis demonstrated that cathepsins B and L, Mr 27000-30000, consist of disulphide-linked dimers, subunit Mr values 22000-25000 and 5000-7000. The pH optimum for the hydrolysis of methylcoumarylamide (-NHMec) substrates (see below) is approx. 6.0 for each enzyme. Km and kcat. are 252 microM and 364s-1 and 2.2 microM and 25.8 s-1 for the hydrolysis of Z-Phe-Arg-NHMec (where Z- represents benzyloxycarbonyl-) by cathepsins B and L respectively, and 184 microM and 158 s-1 for the hydrolysis of Z-Arg-Arg-NHMec by cathepsin B. A 10 min preincubation of cathepsin B (40 degrees C) or cathepsin L (30 degrees C) with E-64 (2.5 microM) results in complete inhibition. Under identical conditions Z-Phe-Phe-CHN2 (0.56 microM) completely inhibits cathepsin L but has little effect on cathepsin B. Incubation of glomerular basement membrane (GBM) with purified human kidney cathepsin L resulted in dose-dependent (10-40 nM) GBM degradation. In contrast, little degradation of GBM (less than 4.0%) was observed with cathepsin B. The pH optimum for GBM degradation by cathepsin L was 3.5. Cathepsin L was significantly more active in degrading GBM than was pancreatic elastase, trypsin or bacterial collagenase. These data suggest that cathepsin L may participate in the lysosomal degradation of GBM associated with normal GBM turnover in vivo.
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PMID:Human kidney cathepsins B and L. Characterization and potential role in degradation of glomerular basement membrane. 284 49

The synthesis of two lysylfluoromethanes is described by an extension of the synthesis method of Rauber, Angliker, Walker & Shaw [(1986) Biochem. J. 239, 633-640]. Ala-Phe-Lys-CH2F was found to be an active-centre-directed inhibitor of plasmin and trypsin, as is the corresponding chloromethane. However, the rate of covalent-bond formation is about an order of magnitude lower at 25 degrees C for the fluoro derivative. It was, in addition, an extremely effective inactivator of cathepsin B at pH 5.4 and 6.4. The chemical reactivity of fluoromethanes was compared with that of chloromethanes as alkylators of GSH. At pH 7.4 and 37 degrees C, a fluoromethane has 1/500th the reactivity of a chloromethane. A comparison of the rates of reaction of the fluoromethane with cathepsin B and with GSH at pH 6.4 revealed an enhancement of 10(8)-fold for the alkylation of the enzyme, ascribable largely to a proximity effect.
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PMID:The synthesis of lysylfluoromethanes and their properties as inhibitors of trypsin, plasmin and cathepsin B. 295 36

The complete amino acid sequences of subunits VII and VIIa from yeast cytochrome c oxidase are reported. Subunits VII and VIIa are 57 residues (Mr = 6603) and 54 residues (Mr = 6303) in length, respectively. Both polypeptides are amphiphilic, have an internal hydrophobic section and hydrophilic NH2 and COOH termini, and terminate at their COOH termini with a basic amino acid. This structural motif is similar to that possessed by subunit VIII of yeast cytochrome c oxidase. All three polypeptides have hydrophobic sections which are long enough to span the inner membrane; all three polypeptides lack methionine at their NH2 termini; and all three polypeptides have COOH termini which could result from proteolysis by a protease with trypsin or cathepsin B-like activity. These observations raise the interesting possibility that subunits VII, VIIa, and VIII are transmembranous polypeptides which are processed at both their NH2 and COOH termini during their biogenesis.
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PMID:The nuclear-coded subunits of yeast cytochrome c oxidase. The amino acid sequences of subunits VII and VIIa, structural similarities between the three smallest polypeptides of the holoenzyme, and implications for biogenesis. 301 77

Hydrolytic activity of lysosomal cathepsins B and H, and trypsin-like proteases in 115 middle ear effusions (MEEs, 40 serous and 75 mucoid) from chronic otitis media with effusion (OME) patients was measured and compared to that in plasma. The activity of both cathepsins in MEEs was significantly higher than that in plasma (p less than 0.01), and cathepsin B activity in mucoid MEEs was also significantly higher than that in serous MEEs (p less than 0.01). The activity of trypsin-like proteases was very weak in both MEEs and plasma. Profiles of various inhibitors indicated the qualitative difference of proteolytic enzymes between MEEs and plasma. Mucoid MEEs had significantly higher activity of thiol proteases than serous ones (p less than 0.01). Cathepsin B-like lysosomal thiol proteases, derived mainly from macrophages, could become a major proteolytic factor to perpetuate and amplify the inflammatory reaction of chronic OME.
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PMID:Lysosomal thiol proteases in middle ear effusions. 308 62

Plasminogen activator (PA) is an estradiol-inducible enzyme and therefore a potential marker for a functional estradiol receptor (ER) in human breast carcinomas. In this investigation tissue-type PA (t-PA) correlated significantly with both ER and progesterone receptors (PR) in human breast carcinomas. In contrast, neither total PA activity nor urokinase-like PA showed any significant correlation with either ER or PR. Other proteases such as a trypsin-like protease, a chymotrypsin-like protease, and cathepsin B also showed no correlation with ER and PR. It was concluded that the t-PA form of PA may be a marker for a functional ER in breast carcinoma and thus be of value in predicting hormone-dependent breast cancers.
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PMID:Tissue-type plasminogen activator in breast cancer: relationship with estradiol and progesterone receptors. 309 95

Recent studies using experimental models of acute pancreatitis suggest that events blocking evoked secretion of digestive enzymes from acinar cells may play an important role in the pathogenesis of this disease. Under these conditions, digestive enzymes become co-localized with lysosomal hydrolases within large intracellular vacuoles, where activation of trypsin by the lysosomal enzyme cathepsin B could initiate the cascade activation of the other pancreatic zymogens. Development of acute pancreatitis might, therefore, be initiated by events occurring within acinar cells rather than in the ductal system or the interstitium of the gland.
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PMID:Pathogenesis of acute pancreatitis. 328 93


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