1e0f
From Proteopedia
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| - | [[Image:1e0f.gif|left|200px]] | + | [[Image:1e0f.gif|left|200px]] |
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| - | '''CRYSTAL STRUCTURE OF THE HUMAN ALPHA-THROMBIN-HAEMADIN COMPLEX: AN EXOSITE II-BINDING INHIBITOR''' | + | {{Structure |
| + | |PDB= 1e0f |SIZE=350|CAPTION= <scene name='initialview01'>1e0f</scene>, resolution 3.1Å | ||
| + | |SITE= <scene name='pdbsite=ATE:Catalytic+Site+Triad'>ATE</scene> | ||
| + | |LIGAND= | ||
| + | |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 HUMAN ALPHA-THROMBIN-HAEMADIN COMPLEX: AN EXOSITE II-BINDING INHIBITOR''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1E0F is a [ | + | 1E0F is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/Haemadipsa_sylvestris Haemadipsa sylvestris] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1E0F OCA]. |
==Reference== | ==Reference== | ||
| - | Crystal structure of the human alpha-thrombin-haemadin complex: an exosite II-binding inhibitor., Richardson JL, Kroger B, Hoeffken W, Sadler JE, Pereira P, Huber R, Bode W, Fuentes-Prior P, EMBO J. 2000 Nov 1;19(21):5650-60. PMID:[http:// | + | Crystal structure of the human alpha-thrombin-haemadin complex: an exosite II-binding inhibitor., Richardson JL, Kroger B, Hoeffken W, Sadler JE, Pereira P, Huber R, Bode W, Fuentes-Prior P, EMBO J. 2000 Nov 1;19(21):5650-60. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/11060016 11060016] |
[[Category: Haemadipsa sylvestris]] | [[Category: Haemadipsa sylvestris]] | ||
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
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[[Category: coagulation/crystal structure/heparin-binding site/ hirudin/thrombin inhibitor]] | [[Category: coagulation/crystal structure/heparin-binding site/ hirudin/thrombin inhibitor]] | ||
| - | ''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 10:47:36 2008'' |
Revision as of 08:47, 20 March 2008
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| , resolution 3.1Å | |||||||
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| Sites: | |||||||
| Activity: | Thrombin, with EC number 3.4.21.5 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
CRYSTAL STRUCTURE OF THE HUMAN ALPHA-THROMBIN-HAEMADIN COMPLEX: AN EXOSITE II-BINDING INHIBITOR
Contents |
Overview
The serine proteinase alpha-thrombin plays a pivotal role in the regulation of blood fluidity, and therefore constitutes a primary target in the treatment of various haemostatic disorders. Haemadin is a slow tight- binding thrombin inhibitor from the land-living leech Haemadipsa sylvestris. Here we present the 3.1 A crystal structure of the human alpha-thrombin- haemadin complex. The N-terminal segment of haemadin binds to the active site of thrombin, forming a parallel beta-strand with residues Ser214-Gly216 of the proteinase. This mode of binding is similar to that observed in another leech-derived inhibitor, hirudin. In contrast to hirudin, however, the markedly acidic C-terminal peptide of haemadin does not bind the fibrinogen-recognition exosite, but interacts with the heparin-binding exosite of thrombin. Thus, haemadin binds to thrombin according to a novel mechanism, despite an overall structural similarity with hirudin. Haemadin inhibits both free and thrombomodulin-bound alpha-thrombin, but not intermediate activation forms such as meizothrombin. This specific anticoagulant ability of haemadin makes it an ideal candidate for an antithrombotic agent, as well as a starting point for the design of novel antithrombotics.
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this Structure
1E0F is a Protein complex structure of sequences from Haemadipsa sylvestris and Homo sapiens. Full crystallographic information is available from OCA.
Reference
Crystal structure of the human alpha-thrombin-haemadin complex: an exosite II-binding inhibitor., Richardson JL, Kroger B, Hoeffken W, Sadler JE, Pereira P, Huber R, Bode W, Fuentes-Prior P, EMBO J. 2000 Nov 1;19(21):5650-60. PMID:11060016
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