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1sr5
From Proteopedia
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ANTITHROMBIN-ANHYDROTHROMBIN-HEPARIN TERNARY COMPLEX STRUCTURE
Contents |
Overview
Antithrombin, the principal physiological inhibitor of the blood, coagulation proteinase thrombin, requires heparin as a cofactor. We report, the crystal structure of the rate-determining encounter complex formed, between antithrombin, anhydrothrombin and an optimal synthetic 16-mer, oligosaccharide. The antithrombin reactive center loop projects from the, serpin body and adopts a canonical conformation that makes extensive, backbone and side chain contacts from P5 to P6' with thrombin's, restrictive specificity pockets, including residues in the 60-loop. These, contacts rationalize many earlier mutagenesis studies on thrombin, specificity. The 16-mer oligosaccharide is just long enough to form the, predicted bridge between the high-affinity pentasaccharide-binding site on, antithrombin and the highly basic exosite 2 on thrombin, validating the, design strategy for this synthetic heparin. The protein-protein and, protein-oligosaccharide interactions together explain the basis for, heparin activation of antithrombin as a thrombin inhibitor.
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this Structure
1SR5 is a Protein complex structure of sequences from Homo sapiens with NAG, NT1 and NT2 as ligands. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.
Reference
The ternary complex of antithrombin-anhydrothrombin-heparin reveals the basis of inhibitor specificity., Dementiev A, Petitou M, Herbert JM, Gettins PG, Nat Struct Mol Biol. 2004 Sep;11(9):863-7. Epub 2004 Aug 15. PMID:15311268
Page seeded by OCA on Mon Nov 12 19:17:05 2007
