2gd4

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spinqualitylabelsall models 2gd4, resolution 3.300Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

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

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

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.

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 with NAG, CA and NTO as ligands. Active as Coagulation factor Xa, with EC number 3.4.21.6 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

Page seeded by OCA on Mon Nov 12 22:17:28 2007