3hat
From Proteopedia
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==Overview== | ==Overview== | ||
| - | The structures of two mimetic inhibitor complexes of human alpha-thrombin | + | The structures of two mimetic inhibitor complexes of human alpha-thrombin have been determined by X-ray crystallography. One mimics a beta-turn with a bicyclic ring system; the other mimics two different active-site binding modes. The beta-turn mimetic is used to approximate a turn found in the conformation of fibrinopeptide A, which is catalytically released by thrombin in the activation of fibrinogen to fibrin. The binding of the second mimetic is a hybrid between normal substrate and the abnormal binding of the potent natural leech inhibitor hirudin. The binding of the beta-turn mimetic is tenuous, because it is like a substrate, while that of the substrate-hirudin hybrid is that of a tenacious inhibitor (which it is). Structurally retrospect modifications for rational design and improvement of both mimetic inhibitors are proposed. |
==Disease== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 3HAT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO3:'>SO3</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. This structure | + | 3HAT is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=SO3:'>SO3</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. This structure supersedes the now removed PDB entry 2HAT. 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] Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3HAT OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Thrombin]] | [[Category: Thrombin]] | ||
| - | [[Category: Mathews, I | + | [[Category: Mathews, I I.]] |
[[Category: Tulinsky, A.]] | [[Category: Tulinsky, A.]] | ||
[[Category: SO3]] | [[Category: SO3]] | ||
[[Category: complex (serine protease/inhibitor)]] | [[Category: complex (serine protease/inhibitor)]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 19:09:40 2008'' |
Revision as of 17:09, 21 February 2008
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ACTIVE SITE MIMETIC INHIBITION OF THROMBIN
Contents |
Overview
The structures of two mimetic inhibitor complexes of human alpha-thrombin have been determined by X-ray crystallography. One mimics a beta-turn with a bicyclic ring system; the other mimics two different active-site binding modes. The beta-turn mimetic is used to approximate a turn found in the conformation of fibrinopeptide A, which is catalytically released by thrombin in the activation of fibrinogen to fibrin. The binding of the second mimetic is a hybrid between normal substrate and the abnormal binding of the potent natural leech inhibitor hirudin. The binding of the beta-turn mimetic is tenuous, because it is like a substrate, while that of the substrate-hirudin hybrid is that of a tenacious inhibitor (which it is). Structurally retrospect modifications for rational design and improvement of both mimetic inhibitors are proposed.
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this Structure
3HAT is a Single protein structure of sequence from Homo sapiens with as ligand. This structure supersedes the now removed PDB entry 2HAT. Active as Thrombin, with EC number 3.4.21.5 Full crystallographic information is available from OCA.
Reference
Active-site mimetic inhibition of thrombin., Mathews II, Tulinsky A, Acta Crystallogr D Biol Crystallogr. 1995 Jul 1;51(Pt 4):550-9. PMID:15299843
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