1dx5
From Proteopedia
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'''CRYSTAL STRUCTURE OF THE THROMBIN-THROMBOMODULIN COMPLEX''' | '''CRYSTAL STRUCTURE OF THE THROMBIN-THROMBOMODULIN COMPLEX''' | ||
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[[Category: Rumennik, G.]] | [[Category: Rumennik, G.]] | ||
[[Category: Seto, M.]] | [[Category: Seto, M.]] | ||
| - | [[Category: | + | [[Category: Anticoagulant complex]] |
| - | [[Category: | + | [[Category: Antifibrinolytic complex]] |
| - | [[Category: | + | [[Category: Egf-like domain]] |
| - | [[Category: | + | [[Category: Serine proteinase]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 14:23:10 2008'' | |
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | |
Revision as of 11:23, 2 May 2008
CRYSTAL STRUCTURE OF THE THROMBIN-THROMBOMODULIN COMPLEX
Overview
The serine proteinase alpha-thrombin causes blood clotting through proteolytic cleavage of fibrinogen and protease-activated receptors and amplifies its own generation by activating the essential clotting factors V and VIII. Thrombomodulin, a transmembrane thrombin receptor with six contiguous epidermal growth factor-like domains (TME1-6), profoundly alters the substrate specificity of thrombin from pro- to anticoagulant by activating protein C. Activated protein C then deactivates the coagulation cascade by degrading activated factors V and VIII. The thrombin-thrombomodulin complex inhibits fibrinolysis by activating the procarboxypeptidase thrombin-activatable fibrinolysis inhibitor. Here we present the 2.3 A crystal structure of human alpha-thrombin bound to the smallest thrombomodulin fragment required for full protein-C co-factor activity, TME456. The Y-shaped thrombomodulin fragment binds to thrombin's anion-binding exosite-I, preventing binding of procoagulant substrates. Thrombomodulin binding does not seem to induce marked allosteric structural rearrangements at the thrombin active site. Rather, docking of a protein C model to thrombin-TME456 indicates that TME45 may bind substrates in such a manner that their zymogen-activation cleavage sites are presented optimally to the unaltered thrombin active site.
About this Structure
1DX5 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structural basis for the anticoagulant activity of the thrombin-thrombomodulin complex., Fuentes-Prior P, Iwanaga Y, Huber R, Pagila R, Rumennik G, Seto M, Morser J, Light DR, Bode W, Nature. 2000 Mar 30;404(6777):518-25. PMID:10761923 Page seeded by OCA on Fri May 2 14:23:10 2008
