1pge

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[[Image:1pge.gif|left|200px]]<br />
 
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<applet load="1pge" size="450" color="white" frame="true" align="right" spinBox="true"
 
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caption="1pge, resolution 3.5&Aring;" />
 
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'''PROSTAGLANDIN H2 SYNTHASE-1 COMPLEXED WITH P-(2'-IODO-5'-THENOYL)HYDROTROPIC ACID (IODOSUPROFEN)'''<br />
 
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==Overview==
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==PROSTAGLANDIN H2 SYNTHASE-1 COMPLEXED WITH P-(2'-IODO-5'-THENOYL)HYDROTROPIC ACID (IODOSUPROFEN)==
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The cyclooxygenase activity of the membrane protein prostaglandin H2, synthase isoform 1 (PGHS-1) is the target of the nonsteroidal, antiinflammatory drugs (NSAIDs). The X-ray crystal structures of PGHS-1 in, complex with the NSAIDs flurbiprofen and bromoaspirin have been determined, previously [Picot, D., et al. (1994) Nature 367, 243-249; Loll, P. J., et, al. (1995) Nat. Struct. Biol. 2, 637-643]. We report here the preparation, and characterization of novel potent iodinated analogs of the NSAIDs, indomethacin and suprofen, as well as the refined X-ray crystal structures, of their complexes with PGHS-1. The PGHS-iodosuprofen complex structure, has been refined at 3.5 A to an R-value of 0.189 and shows the suprofen, analog to share a common mode of binding with flurbiprofen. The, PGHS-iodoindomethacin complex structure has been refined at 4.5 A to an, R-value of 0.254. The low resolution of the iodoindomethacin complex, structure precludes detailed modeling of drug-enzyme interactions, but the, electron-dense iodine atom of the inhibitor has been unambiguously, located, allowing for the placement and approximate orientation of the, inhibitor in the enzyme's active site. We have modeled two equally likely, binding modes for iodoindomethacin, corresponding to the two principal, conformers of the inhibitor. Like flurbiprofen, iodosuprofen and, iodoindomethacin bind at the end of the long channel which leads into the, enzyme active site. Binding at this site presumably blocks access of, substrate to Tyr-385, a residue essential for catalysis. No evidence is, seen for significant protein conformational differences between the, iodoindomethacin and iodosuprofen of flurbiprofen complex structures.
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<StructureSection load='1pge' size='340' side='right'caption='[[1pge]], [[Resolution|resolution]] 3.50&Aring;' scene=''>
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== Structural highlights ==
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<table><tr><td colspan='2'>[[1pge]] is a 2 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=1PGE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1PGE 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]] 3.5&#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=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=ISF:P-(2-IODO-5-THENOYL)HYDROTROPIC+ACID'>ISF</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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=1pge FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1pge OCA], [https://pdbe.org/1pge PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1pge RCSB], [https://www.ebi.ac.uk/pdbsum/1pge PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1pge 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/pg/1pge_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=1pge 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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1PGE 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, BOG, HEM and ISF 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] Structure known Active Sites: COA, COB, PEA and PEB. Full crystallographic information is available from [http://ispc.weizmann.ac.il/oca-bin/ocashort?id=1PGE 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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Synthesis and use of iodinated nonsteroidal antiinflammatory drug analogs as crystallographic probes of the prostaglandin H2 synthase cyclooxygenase active site., Loll PJ, Picot D, Ekabo O, Garavito RM, Biochemistry. 1996 Jun 11;35(23):7330-40. PMID:[http://ispc.weizmann.ac.il//pmbin/getpm?pmid=8652509 8652509]
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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: Garavito RM]]
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[[Category: Single protein]]
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[[Category: Loll PJ]]
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[[Category: Garavito, R.M.]]
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[[Category: Picot D]]
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[[Category: Loll, P.J.]]
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[[Category: Picot, D.]]
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[[Category: BOG]]
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[[Category: HEM]]
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[[Category: ISF]]
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[[Category: NAG]]
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[[Category: dioxygenase]]
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[[Category: oxidoreductase]]
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[[Category: peroxidase]]
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''Page seeded by [http://ispc.weizmann.ac.il/oca OCA ] on Mon Nov 5 16:59:14 2007''
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Current revision

PROSTAGLANDIN H2 SYNTHASE-1 COMPLEXED WITH P-(2'-IODO-5'-THENOYL)HYDROTROPIC ACID (IODOSUPROFEN)

PDB ID 1pge

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