| Crystallographic analysis of potent and selective factor Xa inhibitors complexed to bovine trypsin. | |
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MedLine Citation:
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PMID: 10417407 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Factor Xa is a serine protease which activates thrombin (factor IIa) and plays a key regulatory role in the blood-coagulation cascade. Factor Xa is, therefore, an important target for the design of anti-thrombotics. Both factor Xa and thrombin share sequence and structural homology with trypsin. As part of a factor Xa inhibitor-design program, a number of factor Xa inhibitors were crystallographically studied complexed to bovine trypsin. The structures of one diaryl benzimidazole, one diaryl carbazole and three diaryloxypyridines are described. All five compounds bind to trypsin in an extended conformation, with an amidinoaryl group in the S1 pocket and a second basic/hydrophobic moiety bound in the S4 pocket. These binding modes all bear a resemblance to the reported binding mode of DX-9065a in bovine trypsin and human factor Xa. |
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Authors:
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M Whitlow; D O Arnaiz; B O Buckman; D D Davey; B Griedel; W J Guilford; S K Koovakkat; A Liang; R Mohan; G B Phillips; M Seto; K J Shaw; W Xu; Z Zhao; D R Light; M M Morrissey |
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Publication Detail:
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Type: In Vitro; Journal Article |
Journal Detail:
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Title: Acta crystallographica. Section D, Biological crystallography Volume: 55 ISSN: 0907-4449 ISO Abbreviation: Acta Crystallogr. D Biol. Crystallogr. Publication Date: 1999 Aug |
Date Detail:
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Created Date: 1999-09-23 Completed Date: 1999-09-23 Revised Date: 2007-07-24 |
Medline Journal Info:
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Nlm Unique ID: 9305878 Medline TA: Acta Crystallogr D Biol Crystallogr Country: DENMARK |
Other Details:
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Languages: eng Pagination: 1395-404 Citation Subset: IM |
Affiliation:
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Berlex Biosciences, 15049 San Pablo Avenue, PO Box 4099, Richmond, California 94804, USA. marc_whitlow@berlex.com |
| Data Bank Information | |
Bank Name/Acc. No.:
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PDB/1QA0; 1QB1; 1QB6; 1QB9; 1QBN; 1QBO |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cattle Crystallography, X-Ray Drug Design Electrochemistry Factor Xa / antagonists & inhibitors* Humans Macromolecular Substances Models, Molecular Molecular Conformation Protein Binding Protein Conformation Trypsin / chemistry* |
| Chemical | |
Reg. No./Substance:
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0/Macromolecular Substances; EC 3.4.21.4/Trypsin; EC 3.4.21.6/Factor Xa |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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