View source for 1dx5

[[Image:1dx5.gif|left|200px]]

<!--
The line below this paragraph, containing "STRUCTURE_1dx5", creates the "Structure Box" on the page.
You may change the PDB parameter (which sets the PDB file loaded into the applet) 
or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
or leave the SCENE parameter empty for the default display.
-->
{{STRUCTURE_1dx5|  PDB=1dx5  |  SCENE=  }} 

'''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 [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DX5 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:[http://www.ncbi.nlm.nih.gov/pubmed/10761923 10761923]
[[Category: Homo sapiens]]
[[Category: Protein complex]]
[[Category: Thrombin]]
[[Category: Bode, W.]]
[[Category: Fuentes-Prior, P.]]
[[Category: Huber, R.]]
[[Category: Iwanaga, Y.]]
[[Category: Light, D R.]]
[[Category: Morser, J.]]
[[Category: Pagila, R.]]
[[Category: Rumennik, G.]]
[[Category: Seto, M.]]
[[Category: Anticoagulant complex]]
[[Category: Antifibrinolytic complex]]
[[Category: Egf-like domain]]
[[Category: Serine proteinase]]
''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 14:23:10 2008''