1XMN

Crystal structure of thrombin bound to heparin

1XMN の概要

• エントリーDOI: 10.2210/pdb1xmn/pdb
• 関連するPDBエントリー: 1PPB
• 関連するBIRD辞書のPRD_ID: PRD_000020
• 分子名称: Thrombin light chain, GLYCEROL, Thrombin heavy chain, ... (11 entities in total)
• 機能のキーワード: blood clotting, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 8
• 化学式量合計: 143580.36

構造登録者

Carter, W.J.,Cama, E.,Huntington, J.A. (登録日: 2004-10-04, 公開日: 2004-11-23, 最終更新日: 2024-10-30)

主引用文献

Carter, W.J.,Cama, E.,Huntington, J.A.
Crystal structure of thrombin bound to heparin
J.Biol.Chem., 280:2745-2749, 2005

PubMed Abstract: 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.

PubMed: 15548541
DOI: 10.1074/jbc.M411606200

実験手法

X-RAY DIFFRACTION (1.85 Å)