1e0f

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{{STRUCTURE_1e0f| PDB=1e0f | SCENE= }}
{{STRUCTURE_1e0f| PDB=1e0f | SCENE= }}
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'''CRYSTAL STRUCTURE OF THE HUMAN ALPHA-THROMBIN-HAEMADIN COMPLEX: AN EXOSITE II-BINDING INHIBITOR'''
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===CRYSTAL STRUCTURE OF THE HUMAN ALPHA-THROMBIN-HAEMADIN COMPLEX: AN EXOSITE II-BINDING INHIBITOR===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_11060016}}
==About this Structure==
==About this Structure==
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[[Category: Richardson, J.]]
[[Category: Richardson, J.]]
[[Category: Coagulation/crystal structure/heparin-binding site/ hirudin/thrombin inhibitor]]
[[Category: Coagulation/crystal structure/heparin-binding site/ hirudin/thrombin inhibitor]]
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Revision as of 20:56, 30 June 2008

Image:1e0f.png

Template:STRUCTURE 1e0f

CRYSTAL STRUCTURE OF THE HUMAN ALPHA-THROMBIN-HAEMADIN COMPLEX: AN EXOSITE II-BINDING INHIBITOR

Template:ABSTRACT PUBMED 11060016

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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