2gd4

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{{STRUCTURE_2gd4| PDB=2gd4 | SCENE= }}
{{STRUCTURE_2gd4| PDB=2gd4 | SCENE= }}
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'''Crystal Structure of the Antithrombin-S195A Factor Xa-Pentasaccharide Complex'''
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===Crystal Structure of the Antithrombin-S195A Factor Xa-Pentasaccharide Complex===
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==Overview==
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Regulation of blood coagulation is critical for maintaining blood flow, while preventing excessive bleeding or thrombosis. One of the principal regulatory mechanisms involves heparin activation of the serpin antithrombin (AT). Inhibition of several coagulation proteases is accelerated by up to 10,000-fold by heparin, either through bridging AT and the protease or by inducing allosteric changes in the properties of AT. The anticoagulant effect of short heparin chains, including the minimal AT-specific pentasaccharide, is mediated exclusively through the allosteric activation of AT towards efficient inhibition of coagulation factors (f) IXa and Xa. Here we present the crystallographic structure of the recognition (Michaelis) complex between heparin-activated AT and S195A fXa, revealing the extensive exosite contacts that confer specificity. The heparin-induced conformational change in AT is required to allow simultaneous contacts within the active site and two distinct exosites of fXa (36-loop and the autolysis loop). This structure explains the molecular basis of protease recognition by AT, and the mechanism of action of the important therapeutic low-molecular-weight heparins.
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{{ABSTRACT_PUBMED_16619025}}
==Disease==
==Disease==
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[[Category: Michaelis complex]]
[[Category: Michaelis complex]]
[[Category: Serpin]]
[[Category: Serpin]]
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 04:58:05 2008''
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''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 21:02:24 2008''

Revision as of 18:02, 27 July 2008

Image:2gd4.png

Template:STRUCTURE 2gd4

Contents

Crystal Structure of the Antithrombin-S195A Factor Xa-Pentasaccharide Complex

Template:ABSTRACT PUBMED 16619025

Disease

Known disease associated with this structure: Factor X deficiency OMIM:[227600]

About this Structure

2GD4 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

Reference

Antithrombin-S195A factor Xa-heparin structure reveals the allosteric mechanism of antithrombin activation., Johnson DJ, Li W, Adams TE, Huntington JA, EMBO J. 2006 May 3;25(9):2029-37. Epub 2006 Apr 13. PMID:16619025

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