Source:http://linkedlifedata.com/resource/pubmed/id/12939270
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
45
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| pubmed:dateCreated |
2003-11-3
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| pubmed:abstractText |
Prothrombin (Pro) activation by factor Xa generates the thrombin catalytic site and exosites I and II. The role of fragment 1 (F1) in the pathway of exosite I expression during Pro activation was characterized in equilibrium binding studies using hirudin(54-65) labeled with 6-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)hexanoate ([NBD]Hir(54-65)(SO3-)) or 5-(carboxy)fluorescein ([5F]Hir(54-65)(SO3-)). [NBD]Hir(54-65)(SO3-) distinguished exosite I environments on Pro, prethrombin 1 (Pre 1), and prethrombin 2 (Pre 2) but bound with the same affinities as [5F]Hir(54-65)(SO3-). Conversion of Pro to Pre 1 caused a 7-fold increase in affinity for the peptides. Conversely, fragment 1.2 (F1.2) decreased the affinity of Pre 2 for [5F]Hir(54-65)(SO3-) by 3-fold. This was correlated with a 16-fold increased affinity of F1.2 for Pre 2 in comparison to thrombin, demonstrating an enhancing effect of F1 on F1.2 binding. The active intermediate, meizothrombin, demonstrated a 50- to 220-fold increase in exosite affinity. Free thrombin and thrombin.F1.2 complex bound [5F]Hir(54-65)(SO3-) with indistinguishable affinity, indicating that the effect of F1 on peptide binding was eliminated upon expression of catalytic activity and exosite I. The results demonstrate a new zymogen-specific role for F1 in modulating the affinity of ligands for exosite I. This may reflect a direct interaction between the F1 and Pre 2 domains in Pro that is lost upon folding of the zymogen activation domain. The effect of F1 on (pro)exosite I and the role of (pro)exosite I in factor Va-dependent substrate recognition suggest that the Pro activation pathway may be regulated by (pro)exosite I interactions with factor Va.
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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/4-Chloro-7-nitrobenzofurazan,
http://linkedlifedata.com/resource/pubmed/chemical/4-carboxyfluorescein,
http://linkedlifedata.com/resource/pubmed/chemical/6-Aminocaproic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/7-nitrobenzoxadiazole-6-aminohexanoi...,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/Factor Va,
http://linkedlifedata.com/resource/pubmed/chemical/Fluoresceins,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorescent Dyes,
http://linkedlifedata.com/resource/pubmed/chemical/Hirudins,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Fragments,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/Prothrombin,
http://linkedlifedata.com/resource/pubmed/chemical/Thrombin,
http://linkedlifedata.com/resource/pubmed/chemical/hirudin (54-65),
http://linkedlifedata.com/resource/pubmed/chemical/meizothrombin,
http://linkedlifedata.com/resource/pubmed/chemical/prethrombins,
http://linkedlifedata.com/resource/pubmed/chemical/prothrombin fragment 1,
http://linkedlifedata.com/resource/pubmed/chemical/prothrombin fragment 1.2
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| pubmed:status |
MEDLINE
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| pubmed:month |
Nov
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
7
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| pubmed:volume |
278
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
44489-95
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| pubmed:dateRevised |
2007-11-14
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| pubmed:meshHeading |
pubmed-meshheading:12939270-4-Chloro-7-nitrobenzofurazan,
pubmed-meshheading:12939270-6-Aminocaproic Acid,
pubmed-meshheading:12939270-Binding Sites,
pubmed-meshheading:12939270-Enzyme Precursors,
pubmed-meshheading:12939270-Factor Va,
pubmed-meshheading:12939270-Fluoresceins,
pubmed-meshheading:12939270-Fluorescent Dyes,
pubmed-meshheading:12939270-Hirudins,
pubmed-meshheading:12939270-Humans,
pubmed-meshheading:12939270-Peptide Fragments,
pubmed-meshheading:12939270-Protein Precursors,
pubmed-meshheading:12939270-Prothrombin,
pubmed-meshheading:12939270-Spectrometry, Fluorescence,
pubmed-meshheading:12939270-Thrombin
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| pubmed:year |
2003
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| pubmed:articleTitle |
Role of prothrombin fragment 1 in the pathway of regulatory exosite I formation during conversion of human prothrombin to thrombin.
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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,
Comparative Study,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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