1jou

From Proteopedia

Revision as of 14:08, 15 February 2008

Crystal Structure of Native S195A Thrombin with an Unoccupied Active Site

Overview

Thrombin participates in its own positive and negative feedback loops, and, its allosteric state helps determine the hemostatic balance. Here we, present the 1.8 A crystallographic structure of S195A thrombin in two, conformational states: active site occupied and active site free. The, active site-occupied form shows how thrombin can accommodate substrates, such as protein C. The active site-free form is in a previously unobserved, closed conformation of thrombin, which satisfies all the conditions of the, so-called "slow" form. A mechanism of allostery is revealed, which relies, on the concerted movement of the disulphide bond between Cys168 and 182, and aromatic residues Phe227, Trp215, and Trp60d. These residues, constitute an allosteric switch, which is flipped directly through sodium, binding, resulting in the fast form with an open active site.

Disease

Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]

About this Structure

1JOU is a Protein complex structure of sequences from Homo sapiens with , , and as ligands. Full crystallographic information is available from OCA.

Reference

The molecular basis of thrombin allostery revealed by a 1.8 A structure of the "slow" form., Huntington JA, Esmon CT, Structure. 2003 Apr;11(4):469-79. PMID:12679024

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