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1ebv

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(New page: 200px<br /><applet load="1ebv" size="450" color="white" frame="true" align="right" spinBox="true" caption="1ebv, resolution 3.2&Aring;" /> '''OVINE PGHS-1 COMPLEXE...)
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[[Image:1ebv.jpg|left|200px]]<br /><applet load="1ebv" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1ebv, resolution 3.2&Aring;" />
 
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'''OVINE PGHS-1 COMPLEXED WITH SALICYL HYDROXAMIC ACID'''<br />
 
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==Overview==
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==OVINE PGHS-1 COMPLEXED WITH SALICYL HYDROXAMIC ACID==
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Aspirin is unique among clinically used nonsteroidal antiinflammatory, drugs in that it irreversibly inactivates prostaglandin (PG) H2 synthase, (PGHS) via acetylation of an active-site serine residue. We report the, synthesis and characterization of a novel acetylating agent, O-acetylsalicylhydroxamic acid (AcSHA), which inhibits PGE2 synthesis in, vivo and blocks the cyclooxygenase activity of PGHS in vitro. AcSHA, requires the presence of the active-site residue Ser-529 to be active, against human PGHS-1; the S529A mutant is resistant to inactivation by the, inhibitor. Analysis of PGHS inactivation by AcSHA, coupled with the X-ray, crystal structure of the complex of ovine PGHS-1 with AcSHA, confirms that, the inhibitor elicits its effects via acetylation of Ser-529 in the, cyclooxygenase active site. The crystal structure reveals an intact, inhibitor molecule bound in the enzyme's cyclooxygenase active-site, channel, hydrogen bonding with Arg-119 of the enzyme. The, structure-activity profile of AcSHA can be rationalized in terms of the, crystal structure of the enzyme-ligand complex. AcSHA may prove useful as, a lead compound to facilitate the development of new acetylating, inhibitors.
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<StructureSection load='1ebv' size='340' side='right'caption='[[1ebv]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1ebv]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Ovis_aries Ovis aries]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1EBV OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1EBV FirstGlance]. <br>
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</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 3.2&#8491;</td></tr>
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<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=OAS:O-ACETYLSERINE'>OAS</scene>, <scene name='pdbligand=SCL:ACETIC+ACID+SALICYLOYL-AMINO-ESTER'>SCL</scene></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=1ebv FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ebv OCA], [https://pdbe.org/1ebv PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ebv RCSB], [https://www.ebi.ac.uk/pdbsum/1ebv PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ebv ProSAT]</span></td></tr>
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</table>
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== Function ==
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[https://www.uniprot.org/uniprot/PGH1_SHEEP PGH1_SHEEP] May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells.
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== Evolutionary Conservation ==
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[[Image:Consurf_key_small.gif|200px|right]]
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Check<jmol>
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<jmolCheckbox>
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<scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/eb/1ebv_consurf.spt"</scriptWhenChecked>
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<scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
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<text>to colour the structure by Evolutionary Conservation</text>
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</jmolCheckbox>
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</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=1ebv ConSurf].
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<div style="clear:both"></div>
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==About this Structure==
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==See Also==
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1EBV is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Ovis_aries Ovis aries] with NAG, SCL and HEM as [http://en.wikipedia.org/wiki/ligands ligands]. Active as [http://en.wikipedia.org/wiki/Prostaglandin-endoperoxide_synthase Prostaglandin-endoperoxide synthase], with EC number [http://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.14.99.1 1.14.99.1] Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1EBV OCA].
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*[[Cyclooxygenase 3D structures|Cyclooxygenase 3D structures]]
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__TOC__
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==Reference==
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</StructureSection>
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O-acetylsalicylhydroxamic acid, a novel acetylating inhibitor of prostaglandin H2 synthase: structural and functional characterization of enzyme-inhibitor interactions., Loll PJ, Sharkey CT, O'Connor SJ, Dooley CM, O'Brien E, Devocelle M, Nolan KB, Selinsky BS, Fitzgerald DJ, Mol Pharmacol. 2001 Dec;60(6):1407-13. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=11723249 11723249]
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[[Category: Large Structures]]
[[Category: Ovis aries]]
[[Category: Ovis aries]]
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[[Category: Prostaglandin-endoperoxide synthase]]
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[[Category: Fitzgerald DJ]]
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[[Category: Single protein]]
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[[Category: Loll PJ]]
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[[Category: Connor, S.J.O.]]
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[[Category: O'Connor SJ]]
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[[Category: Fitzgerald, D.J.]]
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[[Category: Sharkey CT]]
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[[Category: Loll, P.J.]]
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[[Category: Sharkey, C.T.]]
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[[Category: HEM]]
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[[Category: NAG]]
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[[Category: SCL]]
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[[Category: monotopic membrane protein]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Tue Nov 20 13:53:00 2007''
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Current revision

OVINE PGHS-1 COMPLEXED WITH SALICYL HYDROXAMIC ACID

PDB ID 1ebv

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