1h8d
From Proteopedia
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| - | [[Image:1h8d.gif|left|200px]]<br /><applet load="1h8d" size=" | + | [[Image:1h8d.gif|left|200px]]<br /><applet load="1h8d" size="350" color="white" frame="true" align="right" spinBox="true" |
caption="1h8d, resolution 1.4Å" /> | caption="1h8d, resolution 1.4Å" /> | ||
'''X-RAY STRUCTURE OF THE HUMAN ALPHA-THROMBIN COMPLEX WITH A TRIPEPTIDE PHOSPHONATE INHIBITOR.'''<br /> | '''X-RAY STRUCTURE OF THE HUMAN ALPHA-THROMBIN COMPLEX WITH A TRIPEPTIDE PHOSPHONATE INHIBITOR.'''<br /> | ||
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==About this Structure== | ==About this Structure== | ||
| - | 1H8D is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with PHW as [http://en.wikipedia.org/wiki/ligand ligand]. 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] Known structural/functional Site: <scene name='pdbsite=AC1:Tripeptide Phosphonate Inhibitor Binding'>AC1</scene>. Full crystallographic information is available from [http:// | + | 1H8D is a [http://en.wikipedia.org/wiki/Protein_complex Protein complex] structure of sequences from [http://en.wikipedia.org/wiki/Hirudo_medicinalis Hirudo medicinalis] and [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens] with <scene name='pdbligand=PHW:'>PHW</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. 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] Known structural/functional Site: <scene name='pdbsite=AC1:Tripeptide+Phosphonate+Inhibitor+Binding'>AC1</scene>. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1H8D OCA]. |
==Reference== | ==Reference== | ||
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[[Category: serine protease]] | [[Category: serine protease]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Feb 3 09:47:39 2008'' |
Revision as of 07:47, 3 February 2008
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X-RAY STRUCTURE OF THE HUMAN ALPHA-THROMBIN COMPLEX WITH A TRIPEPTIDE PHOSPHONATE INHIBITOR.
Contents |
Overview
X-ray crystallographic studies of human alpha-thrombin with a novel, synthetic inhibitor, an acyl (alpha-aminoalkyl)phosphonate, reveal the, existence of a pentacovalent phosphorus intermediate state. Crystal, structures of the complex of alpha-thrombin with the phosphonate compound, were determined independently using crystals of different ages. The first, structure, solved from a crystal less than seven days old, showed a, pentacoordinated phosphorus moiety. The second structure, determined from, a crystal that was 12 weeks old, showed a tetracoordinated phosphorus, moiety. In the first structure, a water molecule, made nucleophilic by, coordination to His57 of alpha-thrombin, is bonded to the pentacoordinated, phosphorus atom. Its position is approximately equivalent to that occupied, by the water molecule responsible for hydrolytic deacylation during normal, hydrolysis. The pentacoordinated phosphorus adduct collapses to give the, expected pseudo tetrahedral complex, where the phosphorus atom is, covalently bonded to Ser195 O(gamma). The crystallographic data presented, here therefore suggest that the covalent bond formed between the, inhibitor's phosphorus atom and O(gamma) of Ser195 proceeds via an, addition-elimination mechanism, which involves the formation of a, pentacoordinate intermediate.
Disease
Known diseases associated with this structure: Dysprothrombinemia OMIM:[176930], Hyperprothrombinemia OMIM:[176930], Hypoprothrombinemia OMIM:[176930]
About this Structure
1H8D is a Protein complex structure of sequences from Hirudo medicinalis and Homo sapiens with as ligand. Active as Thrombin, with EC number 3.4.21.5 Known structural/functional Site: . Full crystallographic information is available from OCA.
Reference
Inhibition of human alpha-thrombin by a phosphonate tripeptide proceeds via a metastable pentacoordinated phosphorus intermediate., Skordalakes E, Dodson GG, Green DS, Goodwin CA, Scully MF, Hudson HR, Kakkar VV, Deadman JJ, J Mol Biol. 2001 Aug 17;311(3):549-55. PMID:11493008
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