1jmj

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Revision as of 15:36, 12 November 2007

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spinqualitylabelsall models 1jmj, resolution 2.35Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal Structure of Native Heparin Cofactor II

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

The serine proteases sequentially activated to form a fibrin clot are, inhibited primarily by members of the serpin family, which use a unique, beta-sheet expansion mechanism to trap and destroy their targets. Since, the discovery that serpins were a family of serine protease inhibitors, there has been controversy as to the role of conformational change in, their mechanism. It now is clear that protease inhibition depends entirely, on rapid serpin beta-sheet expansion after proteolytic attack. The, regulatory advantage afforded by the conformational mobility of serpins is, demonstrated here by the structures of native and S195A thrombin-complexed, heparin cofactor II (HCII). HCII inhibits thrombin, the final protease of, the coagulation cascade, in a glycosaminoglycan-dependent manner that, involves the release of a sequestered hirudin-like N-terminal tail for, interaction with thrombin. The native structure of HCII resembles that of, native antithrombin and suggests an alternative mechanism of allosteric, activation, whereas the structure of the S195A thrombin-HCII complex, defines the molecular basis of allostery. Together, these structures, reveal a multistep allosteric mechanism that relies on sequential, contraction and expansion of the central beta-sheet of HCII.

Disease

Known diseases associated with this structure: Thrombophilia due to heparin cofactor II deficiency OMIM:[142360]

About this Structure

1JMJ is a Single protein structure of sequence from Homo sapiens with NAG and CA as ligands. Full crystallographic information is available from OCA.

Reference

Crystal structures of native and thrombin-complexed heparin cofactor II reveal a multistep allosteric mechanism., Baglin TP, Carrell RW, Church FC, Esmon CT, Huntington JA, Proc Natl Acad Sci U S A. 2002 Aug 20;99(17):11079-84. Epub 2002 Aug 8. PMID:12169660

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