Document Detail

C-terminal residues 621-635 of protein S are essential for binding to factor Va.
MedLine Citation:
PMID:  10593904     Owner:  NLM     Status:  MEDLINE    
Protein S is anticoagulant in the absence of activated protein C because of direct interactions with coagulation Factors Xa and Va. Synthetic peptides corresponding to amino acid sequences of protein S were tested for their ability to inhibit prothrombinase activity. The peptide containing the C-terminal sequence of protein S, residues 621-635 (PSP14), reversibly inhibited prothrombinase activity in the presence but not in the absence of Factor Va (K(i) approximately 2 microM). PSP14 inhibition of prothrombinase was independent of phospholipids but could be competitively overcome by increasing Factor Xa concentrations, suggesting that the C-terminal region of protein S may compete for a Factor Xa binding site on Factor Va. Studies using peptides with amino acid substitutions suggested that lysines 630, 631, and 633 were critical residues. PSP14 inhibited Factor Va activity in Factor Xa-one-stage clotting assays. PSP14 inhibited protein S binding to immobilized Factor Va. When preincubated with protein S, antibodies raised against PSP14 inhibited binding of protein S to Factor Va and blocked inhibition of prothrombinase activity by protein S. These results show that the C-terminal region of protein S containing residues 621-635 is essential for binding of protein S to Factor Va and that this interaction contributes to anticoagulant action.
M J Heeb; Y Kojima; J Rosing; G Tans; J H Griffin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  274     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1999 Dec 
Date Detail:
Created Date:  2000-01-27     Completed Date:  2000-01-27     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  36187-92     Citation Subset:  IM    
Departments of Molecular and Experimental Medicine and Vascular Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
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MeSH Terms
Amino Acid Sequence
Binding Sites
Blood Coagulation
Factor Va / chemistry,  metabolism*
Molecular Sequence Data
Peptide Fragments / chemistry,  metabolism
Protein Binding
Protein S / chemistry,  metabolism*
Grant Support
Reg. No./Substance:
0/Peptide Fragments; 0/Protein S; 65522-14-7/Factor Va

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

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