1TB6

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

Summary for 1TB6

• Entry DOI: 10.2210/pdb1tb6/pdb
• Descriptor: 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)
• Functional Keywords: heparin, hydrolase-blood clotting complex, hydrolase/blood clotting
• Biological source: Homo sapiens (human); More
• Total number of polymer chains: 3
• Total formula weight: 92162.06

Authors

Li, W.,Johnson, D.J.,Esmon, C.T.,Huntington, J.A. (deposition date: 2004-05-19, release date: 2004-08-17, Last modification date: 2024-11-13)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.5 Å)