Document Detail


Immunological evidence for a proteolytic cleavage at the active site of antithrombin in the mechanism of inhibition of coagulation serine proteases.
MedLine Citation:
PMID:  6790279     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Previous studies have shown that a modified form of antithrombin, cleaved at a single Arg-Ser bond near the carboxy-terminal end of the chain, is formed during the reaction with thrombin concurrent with the formation of the inactive enzyme-inhibitor complex. A variety of evidence suggests that this cleavage site is the active site of antithrombin. In this work, antisera against intact antithrombin, the modified form of antithrombin and the antithrombin-thrombin complex were used in immunodiffusion analyses to probe the state of the inhibitor in its complexes with coagulation serine proteases. The results show that new antigenic determinants not present in intact antithrombin are created in modified antithrombin by the single peptide-bond cleavage. the same antigenic determinants are found also in complexes between antithrombin and thrombin or factor Xa. No evidence for the exposure of other new determinants in the complexes was obtained. The most likely conclusion from these results is that antithrombin exists in its complexes with the serine proteases as the modified, two-chain form of the inhibitor. This suggests that the mechanism of inhibition involves proteolytic cleavage of the active site of antithrombin by the protease.
Authors:
P Wallgren; K Nordling; I Björk
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of biochemistry / FEBS     Volume:  116     ISSN:  0014-2956     ISO Abbreviation:  Eur. J. Biochem.     Publication Date:  1981 Jun 
Date Detail:
Created Date:  1981-10-29     Completed Date:  1981-10-29     Revised Date:  2007-07-23    
Medline Journal Info:
Nlm Unique ID:  0107600     Medline TA:  Eur J Biochem     Country:  GERMANY, WEST    
Other Details:
Languages:  eng     Pagination:  493-6     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Antithrombins*
Binding Sites
Cattle
Immune Sera
Immunodiffusion
Protease Inhibitors*
Protein Binding
Serine Endopeptidases
Thrombin / metabolism
Chemical
Reg. No./Substance:
0/Antithrombins; 0/Immune Sera; 0/Protease Inhibitors; EC 3.4.21.-/Serine Endopeptidases; EC 3.4.21.5/Thrombin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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