1p8v

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1p8v, resolution 2.60Å

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CRYSTAL STRUCTURE OF THE COMPLEX OF PLATELET RECEPTOR GPIB-ALPHA AND ALPHA-THROMBIN AT 2.6A

Contents

Overview

Direct interaction between platelet receptor glycoprotein Ibalpha (GpIbalpha) and thrombin is required for platelet aggregation and activation at sites of vascular injury. Abnormal GpIbalpha-thrombin binding is associated with many pathological conditions,including occlusive arterial thrombosis and bleeding disorders. The crystal structure of the GpIbalpha-thrombin complex at 2.6 angstrom resolution reveals simultaneous interactions of GpIbalpha with exosite I of one thrombin molecule,and with exosite II of a second thrombin molecule. In the crystal lattice,the periodic arrangement of GpIbalpha-thrombin complexes mirrors a scaffold that could serve as a driving force for tight platelet adhesion. The details of these interactions reconcile GpIbalpha-thrombin binding modes that are presently controversial,highlighting two distinct interfaces that are potential targets for development of novel antithrombotic drugs.

Disease

Known diseases associated with this structure: Bernard-Soulier syndrome, type A OMIM:[606672], Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930], Nonarteritic anterior ischemic optic neuropathy, susceptibility to OMIM:[606672], von Willebrand disease, platelet-type OMIM:[606672]

About this Structure

1P8V is a Protein complex structure of sequences from Homo sapiens with , and as ligands. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.

Reference

Crystal structure of the GpIbalpha-thrombin complex essential for platelet aggregation., Dumas JJ, Kumar R, Seehra J, Somers WS, Mosyak L, Science. 2003 Jul 11;301(5630):222-6. PMID:12855811

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