1h8d: Difference between revisions

Revision as of 18:33, 2 May 2008

X-RAY STRUCTURE OF THE HUMAN ALPHA-THROMBIN COMPLEX WITH A TRIPEPTIDE PHOSPHONATE INHIBITOR.

OverviewOverview

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.

About this StructureAbout this Structure

1H8D is a Protein complex structure of sequences from Hirudo medicinalis and Homo sapiens. Full crystallographic information is available from OCA.

ReferenceReference

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 Page seeded by OCA on Fri May 2 18:33:58 2008

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OCA

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 [[Image:1h8d.gif|left|200px]]
- {{Structure
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+The line below this paragraph, containing "STRUCTURE_1h8d", creates the "Structure Box" on the page.
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-|LIGAND= <scene name='pdbligand=PHW:BETA-PHENYL-N-{[(PHENYLMETHYL)OXY]CARBONYL}-D-PHENYLALANYL-N-+[(1S,3E)-1-[DIHYDROXY(METHYLOXY)(PHENYLOXY)-LAMBDA5-PHOSPHANYL]-4-+(METHYLOXY)BUT-3-ENYL]-D-PROLINAMIDE'>PHW</scene>, <scene name='pdbligand=TYS:SULFONATED+TYROSINE'>TYS</scene>
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-|ACTIVITY= <span class='plainlinks'>[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] </span>
+or leave the SCENE parameter empty for the default display.
-|GENE=
+-->
-|DOMAIN=
+{{STRUCTURE_1h8d|  PDB=1h8d  |  SCENE=  }}
-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1h8d FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1h8d OCA], [http://www.ebi.ac.uk/pdbsum/1h8d PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1h8d RCSB]</span>
-}}
 '''X-RAY STRUCTURE OF THE HUMAN ALPHA-THROMBIN COMPLEX WITH A TRIPEPTIDE PHOSPHONATE INHIBITOR.'''
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 [[Category: Green, D.]]
 [[Category: Skordalakes, E.]]
-[[Category: serine protease]]
+[[Category: Serine protease]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 18:33:58 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 20:59:53 2008''