Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recently we have described a novel secreted protein (the WFIKKN protein) that consists of multiple types of protease inhibitory modules, including two tandem Kunitz-type protease inhibitor-domains. On the basis of its homologies we have suggested that the WFIKKN protein is a multivalent protease inhibitor that may control the action of different proteases. In the present work we have expressed the second Kunitz-type protease inhibitor domain of the human protein WFIKKN in Escherichia coli, purified it by affinity chromatography on trypsin-Sepharose and its structure was characterized by CD spectroscopy. The recombinant protein was found to inhibit trypsin (Ki = 9.6 nm), but chymotrypsin, elastase, plasmin, pancreatic kallikrein, lung tryptase, plasma kallikrein, thrombin, urokinase or tissue plasminogen activator were not inhibited by the recombinant protein even at 1 microm concentration. In view of the marked trypsin-specificity of the inhibitor it is suggested that its physiological target may be trypsin.
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PMID:Expression, purification and characterization of the second Kunitz-type protease inhibitor domain of the human WFIKKN protein. 1270 70

Basic amino acid calix[8]arene receptors for tryptase surface recognition have been synthesized. The tetrameric arrangement and the negative charge distribution close to the active sites of the enzyme, have suggested the design of complementary multifunctional receptors that might bind to the active region of the protein blocking the approach of the substrate. Kinetic inhibition analysis on recombinant lung tryptase have showed a time-dependent competitive inhibition with both initial and steady-state rate constants in the nanomolar range.
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PMID:Designed calix[8]arene-based ligands for selective tryptase surface recognition. 1535 89

To elucidate the details of tryptase release from the heart during ischemia-reperfusion (I/R), we attempted the enzymatic measurement of tryptase release from the isolated guinea pig heart perfused by the Langendorff mode I/R model. Tryptase-like activity in the effluent was monitored by the hydrolysis of L-Pyr-Gly-Arg-MCA. Tryptase-like protease and histamine were rapidly released from heart during ischemia within 10 min. After reperfusion, tryptase-like protease levels decreased, achieving stabilization. The tryptase-like protease activity in the effluent was inactivated by serine protease inhibitors. The pattern of inhibition was similar to those of guinea pig and human lung tryptase. In conclusion, tryptase was released into the coronary effluent during ischemia, but not during reperfusion in guinea pig heart.
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PMID:Enzymatic measurement of tryptase-like protease release from isolated perfused guinea pig heart during ischemia-reperfusion. 1627 8

PAR-2, a member of a family of G-protein-coupled receptors, can be activated by serine proteases via proteolytic cleavage. PAR-2 expression is known to be upregulated in respiratory epithelium subsequent to inflammation in asthma and chronic obstructive pulmonary disease (COPD). Since these diseases also are characterized by excessive mucus production and secretion, we investigated whether PAR-2 could be linked to mucin hypersecretion by airway epithelium. Normal human bronchial epithelial (NHBE) cells in primary culture or the human bronchial epithelial cell lines, NCI-H292 and HBE-1, were used. NHBE, NCI-H292, and HBE-1 cells expressed prominent levels of PAR-2 protein. Short-term (30min) exposure of cells to the synthetic PAR-2 agonist peptide (SLIGKV-NH2) elicited a small but statistically significant increase in mucin secretion at high concentrations (100microM and 1000microM), compared to a control peptide with reversed amino acid sequence (VKGILS-NH2). Neither human lung tryptase nor bovine pancreatic trypsin, both PAR-2 agonists, affected NHBE cell mucin secretion when added over a range of concentrations. Knockdown of PAR-2 expression by siRNA blocked the stimulatory effect of the AP. The results suggest that, since PAR-2 activation only weakly increases mucin secretion by human airway epithelial cells in vitro, PAR-2 probably is not a significant contributor to mucin hypersecretion in inflamed airways.
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PMID:Protease-activated receptor-2 (PAR-2) is a weak enhancer of mucin secretion by human bronchial epithelial cells in vitro. 1807 3


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