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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
45
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pubmed:dateCreated |
1997-12-12
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pubmed:abstractText |
Meizothrombin and meizothrombin(desF1) are intermediates formed during the conversion of prothrombin to thrombin by factor Xa, factor Va, phospholipids, and Ca2+ (prothrombinase). These intermediates are active toward synthetic peptide substrates but have limited ability to interact with platelets or macromolecular substrates such as fibrinogen. Meizothrombin and meizothrombin(desF1) activate protein C, however, and may exert primarily an anticoagulant effect. In this study, we investigated the inhibition of meizothrombin and meizothrombin(desF1) by two glycosaminoglycan-dependent protease inhibitors, heparin cofactor II (HCII) and antithrombin (AT). Purified recombinant meizothrombin and meizothrombin(desF1) were inhibited by HCII in the presence of dermatan sulfate with maximal second-order rate constants of 8 x 10(6) M-1.min-1 and 1.8 x 10(7) M-1.min-1, respectively, but were inhibited less than one-tenth as fast by AT in the presence of heparin. Similarly, the products of the prothrombinase reaction were inhibited in situ more effectively by HCII than by AT. When HCII and dermatan sulfate were present continuously during the prothrombinase reaction, meizothrombin was trapped as a sodium dodecyl sulfate-stable complex with HCII and no amidolytic activity could be detected with a thrombin substrate. Our findings indicate that HCII is an effective inhibitor of meizothrombin and meizothrombin(desF1) and, therefore, might regulate the anticoagulant activity of these proteases.
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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/Antithrombin III,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/Esterases,
http://linkedlifedata.com/resource/pubmed/chemical/Glycosaminoglycans,
http://linkedlifedata.com/resource/pubmed/chemical/Heparin Cofactor II,
http://linkedlifedata.com/resource/pubmed/chemical/Prothrombin,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Proteinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Thrombin,
http://linkedlifedata.com/resource/pubmed/chemical/meizothrombin
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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 |
272
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
28660-5
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:9353333-Antithrombin III,
pubmed-meshheading:9353333-Enzyme Precursors,
pubmed-meshheading:9353333-Esterases,
pubmed-meshheading:9353333-Glycosaminoglycans,
pubmed-meshheading:9353333-Heparin Cofactor II,
pubmed-meshheading:9353333-Humans,
pubmed-meshheading:9353333-Models, Chemical,
pubmed-meshheading:9353333-Protein Structure, Secondary,
pubmed-meshheading:9353333-Prothrombin,
pubmed-meshheading:9353333-Recombinant Proteins,
pubmed-meshheading:9353333-Serine Proteinase Inhibitors,
pubmed-meshheading:9353333-Thrombin
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pubmed:year |
1997
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pubmed:articleTitle |
Inhibition of meizothrombin and meizothrombin(desF1) by heparin cofactor II.
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pubmed:affiliation |
Department of Internal Medicine, Washington University, St. Louis, Missouri 63110, USA.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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