1dx5
From Proteopedia
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| - | [[Image:1dx5.gif|left|200px]]<br /><applet load="1dx5" size=" | + | [[Image:1dx5.gif|left|200px]]<br /><applet load="1dx5" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1dx5, resolution 2.30Å" /> | caption="1dx5, resolution 2.30Å" /> | ||
'''CRYSTAL STRUCTURE OF THE THROMBIN-THROMBOMODULIN COMPLEX'''<br /> | '''CRYSTAL STRUCTURE OF THE THROMBIN-THROMBOMODULIN COMPLEX'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1DX5 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with NDG, CA, NA and FMT as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Known structural/functional Sites: <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>. Full crystallographic information is available from [http:// | + | 1DX5 is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=NDG:'>NDG</scene>, <scene name='pdbligand=CA:'>CA</scene>, <scene name='pdbligand=NA:'>NA</scene> and <scene name='pdbligand=FMT:'>FMT</scene> as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [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] Known structural/functional Sites: <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>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1DX5 OCA]. |
==Reference== | ==Reference== | ||
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[[Category: serine proteinase]] | [[Category: serine proteinase]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 09:35:53 2008'' |
Revision as of 07:35, 3 February 2008
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CRYSTAL STRUCTURE OF THE THROMBIN-THROMBOMODULIN COMPLEX
Contents |
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.
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930], Myocardial infarction, susceptibility to OMIM:[188040], Thrombophilia due to thrombomodulin defect OMIM:[188040]
About this Structure
1DX5 is a Protein complex structure of sequences from Homo sapiens with , , and as ligands. Active as Thrombin, with EC number 3.4.21.5 Known structural/functional Sites: , , and . 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 Sun Feb 3 09:35:53 2008
Categories: Homo sapiens | Protein complex | Thrombin | Bode, W. | Fuentes-Prior, P. | Huber, R. | Iwanaga, Y. | Light, D.R. | Morser, J. | Pagila, R. | Rumennik, G. | Seto, M. | CA | FMT | NA | NDG | Anticoagulant complex | Antifibrinolytic complex | Egf-like domains | Serine proteinase
