1dx5
From Proteopedia
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| - | [[Image:1dx5.gif|left|200px]] | + | [[Image:1dx5.gif|left|200px]] |
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| - | '''CRYSTAL STRUCTURE OF THE THROMBIN-THROMBOMODULIN COMPLEX''' | + | {{Structure |
| + | |PDB= 1dx5 |SIZE=350|CAPTION= <scene name='initialview01'>1dx5</scene>, resolution 2.30Å | ||
| + | |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> | ||
| + | |LIGAND= <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene> and <scene name='pdbligand=FMT:FORMIC ACID'>FMT</scene> | ||
| + | |ACTIVITY= [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] | ||
| + | |GENE= | ||
| + | }} | ||
| + | |||
| + | '''CRYSTAL STRUCTURE OF THE THROMBIN-THROMBOMODULIN COMPLEX''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1DX5 is a [ | + | 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== | ==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:// | + | 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: Homo sapiens]] | ||
[[Category: Protein complex]] | [[Category: Protein complex]] | ||
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[[Category: anticoagulant complex]] | [[Category: anticoagulant complex]] | ||
[[Category: antifibrinolytic complex]] | [[Category: antifibrinolytic complex]] | ||
| - | [[Category: egf-like | + | [[Category: egf-like domain]] |
[[Category: serine proteinase]] | [[Category: serine proteinase]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Mar 20 10:45:50 2008'' |
Revision as of 08:45, 20 March 2008
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| , resolution 2.30Å | |||||||
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| Sites: | , , and | ||||||
| Ligands: | , , and | ||||||
| Activity: | Thrombin, with EC number 3.4.21.5 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
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. 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 Thu Mar 20 10:45:50 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 domain | Serine proteinase
