1xmn

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spinqualitylabelsall models 1xmn, resolution 1.85Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

Crystal structure of thrombin bound to heparin

Contents 1 Overview 2 Disease 3 About this Structure 4 Reference

Overview

Thrombin is the final protease in the blood coagulation cascade and serves, both pro- and anticoagulant functions through the cleavage of several, targets. The ability of thrombin to specifically recognize a wide range of, substrates derives from interactions that occur outside of the active site, of thrombin. Thrombin possesses two anion binding exosites, which mediate, many of its interactions with cofactors and substrates, and although many, structures of thrombin have been solved, few such interactions have been, described in molecular detail. Glycosaminoglycan binding to exosite II of, thrombin plays a major role in switching off the procoagulant functions of, thrombin by mediating its irreversible inhibition by circulating serpins, and by its binding to the endothelial cell surface receptor, thrombomodulin. Here we report the 1.85-A structure of human, alpha-thrombin bound to a heparin fragment of eight monosaccharide units, in length. The asymmetric unit is composed of two thrombin dimers, each, sharing a single heparin octasaccharide chain. The observed interactions, are fully consistent with previous mutagenesis studies and illustrate on a, molecular level the cofactor interaction that is critical for the, restriction of clotting to the site of blood vessel injury.

Disease

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

About this Structure

1XMN is a Protein complex structure of sequences from Homo sapiens with NA and GOL as ligands. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.

Reference

Crystal structure of thrombin bound to heparin., Carter WJ, Cama E, Huntington JA, J Biol Chem. 2005 Jan 28;280(4):2745-9. Epub 2004 Nov 17. PMID:15548541

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