Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.68 (tissue plasminogen activator)
 11,311 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Capillary damage induced in sheep by intravenous infusion of Escherichia coli endotoxin, oleic acid, or air emboli causes the appearance in lung lymph of a serine protease with trypsin-like activity. The time course of the appearance of the enzyme and the extent of its activity increase indicate a close association with capillary injury. The enzyme was isolated from active lymph after a 9,000-fold purification by affinity chromatography on Reactive Blue-agarose, aprotinin-agarose, and p-amino-benzamidine-agarose columns. The protein, molecular mass of 70-75 kDa, is composed of two polypeptide chains of 31 and 43 kDa linked by disulfide bonds. Studies with synthetic peptide and thioester substrates showed preferential cleavage of substrates having two or more basic amino acids and the importance for activity of secondary enzyme-substrate interactions at sites removed from the scissile bond. The specificity of the enzyme and its pattern of sensitivity to inhibition by a series of isocoumarin derivatives distinguish it from enzymes of the clotting and complement systems and also from tissue plasminogen activator and lung and skin tryptase. The origin of the enzyme, its role in capillary damage, and its physiological function remain to be established.
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PMID:Lung lymph capillary injury-related protease. 267 41

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