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)

Hyaluronic acid-binding region and trypsin-link protein were prepared from bovine nasal cartilage proteoglycan complex after trypsin digestion. Binary complexes were reformed between trypsin-link protein and hyaluronic acid-binding region or hyaluronate. Upon trypsin treatment of these complexes, two fragments deriving from trypsin-link protein were characterized. One of them, of 20 kDa, corresponds in fact to a 140-amino acid long fragment and bears the glycosylated site of trypsin-link protein; it appears to be involved in proteoglycan/link protein interaction. The other, of 22 kDa, corresponds to the 200 C-terminal amino acids of trypsin-link protein; it appears to be involved in the binding of link protein with hyaluronic acid. A structural model of bovine trypsin-like protein depicting two distinct domains involved in hyaluronate and proteoglycan subunit interactions is proposed.
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PMID:Link protein interactions with hyaluronate and proteoglycans. Characterization of two distinct domains in bovine cartilage link proteins. 365 11

We have cloned and identified mRNA sequences for two rat pancreatic trypsinogens. Nucleotide sequence analysis of the cloned sequences revealed two mRNAs that encode similar, though noallelic, pretrypsinogens. Trypsinogen I mRNA is 804 nucleotides in length, plus an estimated poly(A) tract of 100 nucleotides, and contains a short (13 nucleotide) 5' noncoding region and a 3' noncoding region of 54 nucleotides. It encodes a preproenzyme of 246 amino acids comprising a hydrophobic prepeptide (signal peptide) of 15 amino acids, an activation peptide characteristic of trypsinogens, and an active form of trypsin, 223 amino acids in length, that has 78% amino acid sequence identity with porcine trypsin. Trypsinogen II mRNA has a nucleotide sequence 88% homologous with that of trypsinogen I mRNA and encodes a protein with 89% amino acid sequence identity with trypsinogen I. The enzymes encoded by trypsinogen I and II mRNAs retain the key amino acid residues that determine the characteristic substrate cleavage preference of trypsins and, therefore, represent the rat counterparts of this digestive enzyme. Trypsinogen I mRNA is a major pancreatic mRNA comprising an estimated 2-5% of the total, whereas trypsinogen II mRNA is present at much lower levels.
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PMID:Two similar but nonallelic rat pancreatic trypsinogens. Nucleotide sequences of the cloned cDNAs. 689 10

The serum concentrations of immunoreactive pancreatic secretory trypsin inhibitor, cationic elastase, anionic trypsin, cationic trypsin, and total amylase activity, were studied after pancreatic allograft transplantation. Nine patients received whole organ pancreaticoduodenal allografts with exocrine drainage to the bladder. Eight of the patients received simultaneously a renal allograft. The serum concentration of immunoreactive cationic elastase increased gradually during the first postoperative days to a peak on the fifth day after surgery; all other proteins decreased in concentration after the first day. Eighteen episodes of pancreatic and/or kidney rejection, diagnosed by means of kidney biopsy, urinary cytology, kidney function, and urinary amylase levels, were analyzed. The pancreatic proteins displayed different patterns in serum concentration during the days immediately before diagnosis of rejection. The pancreatic secretory trypsin inhibitor showed the most pronounced peak in serum concentration during rejection and even reacted during some episodes without a decline in urinary amylase output. Cationic elastase on the other hand showed no reaction at all. From this homogeneous material it is possible to conclude that changes in serum concentrations during rejection are not the same for all pancreatic exocrine proteins.
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PMID:Exocrine pancreatic proteins in serum during pancreatic allograft rejection. 751 92

Increased secretion of matrix metalloproteinases and serine proteinases is well known to be associated with cancer invasion and metastasis. We aimed to elucidate the implication of trypsin, a serine proteinase and a representative digestive enzyme in invasion and metastasis of human carcinomas. Northern blot, RT-PCR and Western blot analyses and immunohistochemical studies were performed to detect and analyze trypsinogen expression in 5 ovarian carcinoma cell lines and 10 human ovarian carcinoma tissues using a DNA probe for trypsinogen I, and monoclonal and polyclonal antibodies to human trypsin I. Among the 5 ovarian carcinoma cell lines, only the MCAS (mucinous cystadenocarcinoma) cell line showed a high level of trypsinogen production and mRNA expression by Western and Northern blot analyses, respectively. However, Southern blot analysis of RT-PCR products could detect considerable levels of trypsinogen mRNA in all ovarian cancer cell lines. In Northern analysis of ovarian cancer tissues, all advanced cancer samples showed trypsinogen gene expression. Serous cystadenocarcinomas exhibited particularly high levels of gene expression. Immunohistochemical staining also detected trypsin in ovarian carcinoma tissues. In contrast, normal ovaries and tumors with low malignant potential did not show trypsinogen expression. Our results demonstrate the extra-pancreatic production and distribution of trypsinogen in human ovarian carcinomas.
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PMID:Trypsinogen expression in human ovarian carcinomas. 759 Dec

Based on genomic Southern hybridizations and cDNA sequence analyses, the chicken trypsinogen gene family can be divided into two multi-member subfamilies, a six-member trypsinogen I subfamily which encodes the cationic trypsin isoenzymes and a three-member trypsinogen II subfamily which encodes the anionic trypsin isoenzymes. The chicken cDNA and genomic clones containing these two subfamilies were isolated and characterized by DNA sequence analysis. The results indicated that the chicken trypsinogen genes encoded a signal peptide of 15 to 16 amino acid residues, an activation peptide of 9 to 10 residues and a trypsin of 223 amino acid residues. The chicken trypsinogens contain all the common catalytic and structural features for trypsins, including the catalytic triad His, Asp and Ser and the six disulphide bonds. The trypsinogen I and II subfamilies share approximately 70% sequence identity at the nucleotide and amino acid level. The sequence comparison among chicken trypsinogen subfamily members and trypsin sequences from other species suggested that the chicken trypsinogen genes may have evolved in coincidental or concerted fashion.
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PMID:Isolation and characterization of the chicken trypsinogen gene family. 773 85

It has previously been reported that two kinds of human gastric adenocarcinoma cell lines (STKM-1 and MKN28) secrete a trypsin-like enzyme. In this study, four molecular forms of the enzyme (26, 25, 24 and 23 kDa on non-reducing SDS/PAGE) were purified from the serum-free conditioned medium of STKM-1 cells. Analysis of N-terminal amino acid sequences showed that the 26 kDa protein was a two-chain form of trypsinogen 1 which had been produced by proteolytic cleavage of the Arg107-Val108 bond of trypsinogen 1, and the 24 kDa protein was the one-chain form of trypsinogen 1. The 25 and 23 kDa proteins were the activated forms of the two-chain and one-chain trypsinogen 1 respectively. Isoelectric focusing gave pI values of 6.3 and 6.6 for the 26 kDa two-chain form and the 24 kDa one-chain form of trypsinogen 1 respectively. Comparison of the proteolytic activities indicated that the one-chain trypsin 1 had amidolytic activity about four times higher than that of the two-chain enzyme.
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PMID:Identification of one- and two-chain forms of trypsinogen 1 produced by a human gastric adenocarcinoma cell line. 794 38

Affinity-based purification and characterization of the collagenolytic serine protease 1 from Uca pugilator (fiddler crab) hepatopancreas shows that the enzyme cleaves the native bovine alpha 1(I) collagen chain carboxyl-terminal to Gln and Arg residues adjacent to the metallocollagenase site. Cleavage carboxyl-terminal to Leu residues is observed in the alpha 2(I) chain and at a secondary site in alpha 1(I). These sites correlate with the preferences observed toward p-nitroanilide substrates varying at the P1 position, for which the specificity (kcat/Km) is Arg > Leu, Phe, Lys > Gln > Ala. Furthermore, collagen cleavage after Gln was found exclusively between two Gln-Arg bonds. The P'1-P'3 specificity of collagenase, as determined by nucleophile acyl transfer, indicated a strong preference for Arg in the P'1 position. Crab collagenase cleaves peptide bonds adjacent to Leu and Gln at the P1 position more efficiently than trypsin, chymotrypsin, or elastase. Moreover, the efficiency of collagenase toward P1-Arg substrates is equivalent to that of trypsin. Crystals of crab collagenase have been grown complexed with the protein inhibitor ecotin. These crystals diffract to better than 2.8 A resolution and belong to the space group P3(2)21 with unit cell dimensions of a = b = 89.0 A, c = 291.7 A.
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PMID:The substrate specificity of Uca pugilator collagenolytic serine protease 1 correlates with the bovine type I collagen cleavage sites. 803 25

Electron microscopical and immunoelectron microscopical techniques were employed to investigate the pathogenesis of sodium taurocholateinduced acute pancreatitis. It was demonstrated that the necrosis of pancreatic acinar cells was associated with specific intracellular vacuolation. A continuous course of vacuole formation from zymogen granules was observed. There were of ten several vacuoles inside one acinar cell, and most of the vacuoles were distributed among zymogen granules. These vacuoles contained large amounts of filamentous materials, which were proved to be pancreatic digestive enzymes by immunoelectron microscopical labelling for alpha-amylase and able to digest and disrupt the circumferential organelles. The results of this study suggest that the necrosis of acinar cells was caused by the activation of digestive zymogen inside zymogen granules. As trypsin is the only enzyme which could activate all the digestive zymogen, and trypsinogen is the sole zymogen capable of autoactivation, it is suggested that the autoactivation of trypsinogen plays an important role in the pathogenesis of acute pancreatitis.
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PMID:[An electron microscopical study on the pathogenesis of taurocholate-induced acute pancreatitis]. 833 Mar 28

The plant pathogenic fungus Verticillium dahliae produced extracellular alkaline protease activity when grown in liquid medium supplemented with a protein source. A serine protease was purified 80-fold in a single step, using cation-exchange chromatography, from the filtrate of cultures grown with skim milk as a protein source. N-terminal amino acid sequence analysis of the 30-kDa protein (VDP30) that copurified with the serine protease activity suggested that VDP30 is a trypsin-like protein. The purified enzyme hydrolyzed the synthetic substrate N alpha-benzoyl-DL-arginine p-nitroanilide hydrochloride (BAPNA), and the activity on BAPNA was inhibited by leupeptin, further verifying the trypsin-like nature of the enzyme.
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PMID:Production of an extracellular trypsin-like protease by the fungal plant pathogen Verticillium dahliae. 909 Jan 11

Crab collagenolytic serine protease 1 efficiently cleaves peptide bonds directly C-terminal to basic, polar, and hydrophobic amino acids. The crystal structure of this enzyme complexed to the protein inhibitor ecotin at 2.5 A resolution reveals a large primary binding pocket punctuated on one wall by the side chain of aspartate-226. Removal or relocation of this negatively charged group by site-directed mutagenesis generates variant enzymes which retain very high activities toward selected substrates. Full retention of activity toward hydrophobic substrates in collagenase D226G is accompanied by a 10-100-fold reduction in k(cat)/Km toward basic residues. In contrast, restoration of the negative charge in a trypsin-like position in collagenase D226G/G189D regenerates nearly full activity toward basic substrates while introducing a 5-fold decrease in k(cat)/Km toward hydrophobic amino acids. These results imply that the collagenase S1 pocket has multiple distinct binding sites for different amino acid side chains, a suggestion supported by molecular modeling studies based on the crystal structure. The ease of specificity modification in the primary binding site of this serine protease parallels similar observations with the bacterial enzymes alpha-lytic protease and subtilisin, and stands in sharp distinction to the extensive mutagenesis required to alter specificity in trypsin.
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PMID:Structural basis for the broad substrate specificity of fiddler crab collagenolytic serine protease 1. 915 21


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