1dx5: Difference between revisions

Revision as of 14:23, 2 May 2008

CRYSTAL STRUCTURE OF THE THROMBIN-THROMBOMODULIN COMPLEX

OverviewOverview

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 StructureAbout this Structure

1DX5 is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

OCA

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 [[Image:1dx5.gif|left|200px]]
- {{Structure
+<!--
-|PDB= 1dx5 |SIZE=350|CAPTION= <scene name='initialview01'>1dx5</scene>, resolution 2.30&Aring;
+The line below this paragraph, containing "STRUCTURE_1dx5", creates the "Structure Box" on the page.
-|SITE= <scene name='pdbsite=AC1:Catalytic+Triad'>AC1</scene>, <scene name='pdbsite=AC2:Catalytic+Triad'>AC2</scene>, <scene name='pdbsite=AC3:Catalytic+Triad'>AC3</scene> and <scene name='pdbsite=AC4:Catalytic+Triad'>AC4</scene>
+You may change the PDB parameter (which sets the PDB file loaded into the applet)
-|LIGAND= <scene name='pdbligand=ARM:DEOXY-METHYL-ARGININE'>ARM</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=FMT:FORMIC+ACID'>FMT</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene>
+or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
-|ACTIVITY= <span class='plainlinks'>[http://en.wikipedia.org/wiki/Thrombin Thrombin], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=3.4.21.5 3.4.21.5] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1dx5|  PDB=1dx5  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1dx5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1dx5 OCA], [http://www.ebi.ac.uk/pdbsum/1dx5 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1dx5 RCSB]</span>
-}}
 '''CRYSTAL STRUCTURE OF THE THROMBIN-THROMBOMODULIN COMPLEX'''
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 [[Category: Rumennik, G.]]
 [[Category: Seto, M.]]
-[[Category: anticoagulant complex]]
+[[Category: Anticoagulant complex]]
-[[Category: antifibrinolytic complex]]
+[[Category: Antifibrinolytic complex]]
-[[Category: egf-like domain]]
+[[Category: Egf-like domain]]
-[[Category: serine proteinase]]
+[[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 Sun Mar 30 19:50:35 2008''