1hdt
From Proteopedia
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| - | [[Image:1hdt.gif|left|200px]] | + | [[Image:1hdt.gif|left|200px]] |
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| - | '''STRUCTURE OF A RETRO-BINDING PEPTIDE INHIBITOR COMPLEXED WITH HUMAN ALPHA-THROMBIN''' | + | {{Structure |
| + | |PDB= 1hdt |SIZE=350|CAPTION= <scene name='initialview01'>1hdt</scene>, resolution 2.60Å | ||
| + | |SITE= | ||
| + | |LIGAND= <scene name='pdbligand=SO3:SULFITE+ION'>SO3</scene> and <scene name='pdbligand=CH3:METHYL GROUP'>CH3</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= | ||
| + | }} | ||
| + | |||
| + | '''STRUCTURE OF A RETRO-BINDING PEPTIDE INHIBITOR COMPLEXED WITH HUMAN ALPHA-THROMBIN''' | ||
| + | |||
==Overview== | ==Overview== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1HDT is a [ | + | 1HDT is a [[Single protein]] structure of sequence 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=1HDT OCA]. |
==Reference== | ==Reference== | ||
| - | Structure of a retro-binding peptide inhibitor complexed with human alpha-thrombin., Tabernero L, Chang CY, Ohringer SL, Lau WF, Iwanowicz EJ, Han WC, Wang TC, Seiler SM, Roberts DG, Sack JS, J Mol Biol. 1995 Feb 10;246(1):14-20. PMID:[http:// | + | Structure of a retro-binding peptide inhibitor complexed with human alpha-thrombin., Tabernero L, Chang CY, Ohringer SL, Lau WF, Iwanowicz EJ, Han WC, Wang TC, Seiler SM, Roberts DG, Sack JS, J Mol Biol. 1995 Feb 10;246(1):14-20. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/7853394 7853394] |
[[Category: Homo sapiens]] | [[Category: Homo sapiens]] | ||
[[Category: Single protein]] | [[Category: Single protein]] | ||
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[[Category: complex (serine proteinase/inhibitor)]] | [[Category: complex (serine proteinase/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 11:35:51 2008'' |
Revision as of 09:35, 20 March 2008
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| , resolution 2.60Å | |||||||
|---|---|---|---|---|---|---|---|
| Ligands: | and | ||||||
| Activity: | Thrombin, with EC number 3.4.21.5 | ||||||
| Coordinates: | save as pdb, mmCIF, xml | ||||||
STRUCTURE OF A RETRO-BINDING PEPTIDE INHIBITOR COMPLEXED WITH HUMAN ALPHA-THROMBIN
Contents |
Overview
The crystallographic structure of the ternary complex between human alpha-thrombin, hirugen and the peptidyl inhibitor Phe-alloThr-Phe-O-CH3, which is acylated at its N terminus with 4-guanidino butanoic acid (BMS-183507), has been determined at 2.6 A resolution. The structure reveals a unique "retro-binding" mode for this tripeptide active site inhibitor. The inhibitor binds with its alkyl-guanidine moiety in the primary specificity pocket and its two phenyl rings occupying the hydrophobic proximal and distal pockets of the thrombin active site. In this arrangement the backbone of the tripeptide forms a parallel beta-strand to the thrombin main-chain at the binding site. This is opposite to the orientation of the natural substrate, fibrinogen, and all the small active site-directed thrombin inhibitors whose bound structures have been previously reported. BMS-183507 is the first synthetic inhibitor proved to bind in a retro-binding fashion to thrombin, in a fashion similar to that of the N-terminal residues of the natural inhibitor hirudin. Furthermore, this new potent thrombin inhibitor (Ki = 17.2 nM) is selective for thrombin over other serine proteases tested and may be a template to be considered in designing hirudin-based thrombin inhibitors with interactions at the specificity pocket.
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this Structure
1HDT is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Structure of a retro-binding peptide inhibitor complexed with human alpha-thrombin., Tabernero L, Chang CY, Ohringer SL, Lau WF, Iwanowicz EJ, Han WC, Wang TC, Seiler SM, Roberts DG, Sack JS, J Mol Biol. 1995 Feb 10;246(1):14-20. PMID:7853394
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