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4fm5

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==X-ray structure of des-methylflurbiprofen bound to murine COX-2==
==X-ray structure of des-methylflurbiprofen bound to murine COX-2==
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<StructureSection load='4fm5' size='340' side='right' caption='[[4fm5]], [[Resolution|resolution]] 2.81&Aring;' scene=''>
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<StructureSection load='4fm5' size='340' side='right'caption='[[4fm5]], [[Resolution|resolution]] 2.81&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
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<table><tr><td colspan='2'>[[4fm5]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FM5 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4FM5 FirstGlance]. <br>
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<table><tr><td colspan='2'>[[4fm5]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4FM5 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4FM5 FirstGlance]. <br>
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</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=DF0:(2-FLUOROBIPHENYL-4-YL)ACETIC+ACID'>DF0</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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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]] 2.81&#8491;</td></tr>
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<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3rr3|3rr3]], [[3nt1|3nt1]]</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=DF0:(2-FLUOROBIPHENYL-4-YL)ACETIC+ACID'>DF0</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
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<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Ptgs2, Cox-2, Cox2, Pghs-b, Tis10 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])</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=4fm5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fm5 OCA], [https://pdbe.org/4fm5 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4fm5 RCSB], [https://www.ebi.ac.uk/pdbsum/4fm5 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4fm5 ProSAT]</span></td></tr>
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<tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[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] </span></td></tr>
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<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4fm5 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4fm5 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4fm5 RCSB], [http://www.ebi.ac.uk/pdbsum/4fm5 PDBsum]</span></td></tr>
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</table>
</table>
== Function ==
== Function ==
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[[http://www.uniprot.org/uniprot/PGH2_MOUSE PGH2_MOUSE]] Mediates the formation of prostaglandins from arachidonate. May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity.<ref>PMID:12925531</ref> <ref>PMID:20463020</ref> <ref>PMID:20810665</ref> <ref>PMID:21489986</ref>
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[https://www.uniprot.org/uniprot/PGH2_MOUSE PGH2_MOUSE] Mediates the formation of prostaglandins from arachidonate. May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity.<ref>PMID:12925531</ref> <ref>PMID:20463020</ref> <ref>PMID:20810665</ref> <ref>PMID:21489986</ref>
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<div style="background-color:#fffaf0;">
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== Publication Abstract from PubMed ==
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Cyclooxygenase-2 (COX-2) oxygenates arachidonic acid and the endocannabinoids 2-arachidonoylglycerol (2-AG) and arachidonoylethanolamide (AEA). We recently reported that (R)-profens selectively inhibit endocannabinoid oxygenation but not arachidonic acid oxygenation. In this work, we synthesized achiral derivatives of five profen scaffolds and evaluated them for substrate-selective inhibition using in vitro and cellular assays. The size of the substituents dictated the inhibitory strength of the analogs, with smaller substituents enabling greater potency but less selectivity. Inhibitors based on the flurbiprofen scaffold possessed the greatest potency and selectivity, with desmethylflurbiprofen (3a) exhibiting an IC(50) of 0.11 muM for inhibition of 2-AG oxygenation. The crystal structure of desmethylflurbiprofen complexed to mCOX-2 demonstrated a similar binding mode to other profens. Desmethylflurbiprofen exhibited a half-life in mice comparable to that of ibuprofen. The data presented suggest that achiral profens can act as lead molecules toward in vivo probes of substrate-selective COX-2 inhibition.
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Substrate-Selective Inhibition of Cyclooxygenase-2: Development and Evaluation of Achiral Profen Probes.,Windsor MA, Hermanson DJ, Kingsley PJ, Xu S, Crews BC, Ho W, Keenan CM, Banerjee S, Sharkey KA, Marnett LJ ACS Med Chem Lett. 2012 Sep 13;3(9):759-763. Epub 2012 Aug 15. PMID:22984634<ref>PMID:22984634</ref>
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From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
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</div>
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==See Also==
==See Also==
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*[[Cyclooxygenase|Cyclooxygenase]]
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*[[Cyclooxygenase 3D structures|Cyclooxygenase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
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[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Mus musculus]]
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[[Category: Prostaglandin-endoperoxide synthase]]
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[[Category: Banerjee S]]
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[[Category: Banerjee, S]]
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[[Category: Marnett LJ]]
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[[Category: Marnett, L J]]
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[[Category: Windsor MA]]
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[[Category: Windsor, M A]]
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[[Category: Xu S]]
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[[Category: Xu, S]]
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[[Category: Cyclooxygenase]]
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[[Category: Heme binding]]
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[[Category: Membrane protein]]
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[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
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Current revision

X-ray structure of des-methylflurbiprofen bound to murine COX-2

PDB ID 4fm5

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