1TB6

2.5A Crystal Structure of the Antithrombin-Thrombin-Heparin Ternary Complex

1TB6 の概要

• エントリーDOI: 10.2210/pdb1tb6/pdb
• 分子名称: thrombin, Antithrombin-III, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-[alpha-L-fucopyranose-(1-6)]2-acetamido-2-deoxy-beta-D-glucopyranose, ... (10 entities in total)
• 機能のキーワード: heparin, hydrolase-blood clotting complex, hydrolase/blood clotting
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 92162.06

構造登録者

Li, W.,Johnson, D.J.,Esmon, C.T.,Huntington, J.A. (登録日: 2004-05-19, 公開日: 2004-08-17, 最終更新日: 2024-11-13)

主引用文献

Li, W.,Johnson, D.J.,Esmon, C.T.,Huntington, J.A.
Structure of the antithrombin-thrombin-heparin ternary complex reveals the antithrombotic mechanism of heparin.
Nat.Struct.Mol.Biol., 11:857-862, 2004

PubMed Abstract: The maintenance of normal blood flow depends completely on the inhibition of thrombin by antithrombin, a member of the serpin family. Antithrombin circulates at a high concentration, but only becomes capable of efficient thrombin inhibition on interaction with heparin or related glycosaminoglycans. The anticoagulant properties of therapeutic heparin are mediated by its interaction with antithrombin, although the structural basis for this interaction is unclear. Here we present the crystal structure at a resolution of 2.5 A of the ternary complex between antithrombin, thrombin and a heparin mimetic (SR123781). The structure reveals a template mechanism with antithrombin and thrombin bound to the same heparin chain. A notably close contact interface, comprised of extensive active site and exosite interactions, explains, in molecular detail, the basis of the antithrombotic properties of therapeutic heparin.

PubMed: 15311269
DOI: 10.1038/nsmb811

実験手法

X-RAY DIFFRACTION (2.5 Å)