Source:http://linkedlifedata.com/resource/pubmed/id/10373475
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
26
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pubmed:dateCreated |
1999-7-15
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pubmed:abstractText |
The blood coagulation proteinase, thrombin, converts factor V into factor Va through a multistep activation pathway that is regulated by interactions with thrombin exosites. Thrombin exosite interactions with human factor V and its activation products were quantitatively characterized in equilibrium binding studies based on fluorescence changes of thrombin covalently labeled with 2-anilinonaphthalene-6-sulfonic acid (ANS) linked to the catalytic site histidine residue by Nalpha-[(acetylthio)acetyl]-D-Phe-Pro-Arg-CH2Cl ([ANS]FPR-thrombin). Exosite I was shown to play a predominant role in the binding of factor V and factor Va from the effect of the exosite I-specific ligand, hirudin54-65, on the interactions. Factor V and factor Va bound to exosite I of [ANS]FPR-thrombin with similar dissociation constants of 3.4 +/- 1.3 and 1.1 +/- 0.4 microM and fluorescence enhancements of 182 +/- 41 and 127 +/- 17%, respectively. Native thrombin and labeled thrombin bound with similar affinity to factor Va. Among factor V activation products, the factor Va heavy chain was shown to contain the site of exosite I binding, whereas exosite I-independent, lower affinity interactions were observed for activation fragments E and C1, and no detectable binding was observed for the factor Va light chain. The results support the conclusion that the factor V activation pathway is initiated by exosite I-mediated binding of thrombin to a site in the heavy chain region of factor V that facilitates the initial cleavage at Arg709 to generate the heavy chain of factor Va. The results further suggest that binding of thrombin through exosite I to factor V activation intermediates may regulate their conversion to factor Va and that similar binding of thrombin to the factor Va produced may reflect a mode of interaction involved in the regulation of prothrombin activation.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/2-anilinonaphthalene-6-sulfonic acid,
http://linkedlifedata.com/resource/pubmed/chemical/Anilino Naphthalenesulfonates,
http://linkedlifedata.com/resource/pubmed/chemical/Factor V,
http://linkedlifedata.com/resource/pubmed/chemical/Factor Va,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorescent Dyes,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Thrombin
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0021-9258
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
25
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pubmed:volume |
274
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
18635-43
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:10373475-Anilino Naphthalenesulfonates,
pubmed-meshheading:10373475-Animals,
pubmed-meshheading:10373475-Binding Sites,
pubmed-meshheading:10373475-Cattle,
pubmed-meshheading:10373475-Factor V,
pubmed-meshheading:10373475-Factor Va,
pubmed-meshheading:10373475-Fluorescent Dyes,
pubmed-meshheading:10373475-Humans,
pubmed-meshheading:10373475-Models, Chemical,
pubmed-meshheading:10373475-Peptide Fragments,
pubmed-meshheading:10373475-Protein Conformation,
pubmed-meshheading:10373475-Thrombin
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pubmed:year |
1999
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pubmed:articleTitle |
Role of regulatory exosite I in binding of thrombin to human factor V, factor Va, factor Va subunits, and activation fragments.
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pubmed:affiliation |
Department of Pathology, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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