3rr3: Difference between revisions
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==Structure of (R)-flurbiprofen bound to mCOX-2== | |||
=== | <StructureSection load='3rr3' size='340' side='right' caption='[[3rr3]], [[Resolution|resolution]] 2.84Å' scene=''> | ||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[3rr3]] 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=3RR3 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3RR3 FirstGlance]. <br> | |||
</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=FLR:(2R)-2-(3-FLUORO-4-PHENYL-PHENYL)PROPANOIC+ACID'>FLR</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | |||
<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> | |||
<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> | |||
<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=3rr3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3rr3 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3rr3 RCSB], [http://www.ebi.ac.uk/pdbsum/3rr3 PDBsum]</span></td></tr> | |||
</table> | |||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Cyclooxygenase-2 (COX-2) catalyzes the oxygenation of arachidonic acid and the endocannabinoids 2-arachidonoylglycerol and arachidonoylethanolamide. Evaluation of a series of COX-2 inhibitors revealed that many weak competitive inhibitors of arachidonic acid oxygenation are potent inhibitors of endocannabinoid oxygenation. (R) enantiomers of ibuprofen, naproxen and flurbiprofen, which are considered to be inactive as COX-2 inhibitors, are potent 'substrate-selective inhibitors' of endocannabinoid oxygenation. Crystal structures of the COX-2-(R)-naproxen and COX-2-(R)-flurbiprofen complexes verified this unexpected binding and defined the orientation of the (R) enantiomers relative to (S) enantiomers. (R)-Profens selectively inhibited endocannabinoid oxygenation by lipopolysaccharide-stimulated dorsal root ganglion (DRG) cells. Substrate-selective inhibition provides new tools for investigating the role of COX-2 in endocannabinoid oxygenation and a possible explanation for the ability of (R)-profens to maintain endocannabinoid tone in models of neuropathic pain. | |||
(R)-Profens are substrate-selective inhibitors of endocannabinoid oxygenation by COX-2.,Duggan KC, Hermanson DJ, Musee J, Prusakiewicz JJ, Scheib JL, Carter BD, Banerjee S, Oates JA, Marnett LJ Nat Chem Biol. 2011 Nov;7(11):803-9. PMID:22053353<ref>PMID:22053353</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
==See Also== | ==See Also== | ||
*[[Cyclooxygenase|Cyclooxygenase]] | *[[Cyclooxygenase|Cyclooxygenase]] | ||
== References == | |||
== | <references/> | ||
< | __TOC__ | ||
</StructureSection> | |||
[[Category: Mus musculus]] | [[Category: Mus musculus]] | ||
[[Category: Prostaglandin-endoperoxide synthase]] | [[Category: Prostaglandin-endoperoxide synthase]] | ||
[[Category: Banerjee, S | [[Category: Banerjee, S]] | ||
[[Category: Carter, B D | [[Category: Carter, B D]] | ||
[[Category: Duggan, K C | [[Category: Duggan, K C]] | ||
[[Category: Hermanson, D J | [[Category: Hermanson, D J]] | ||
[[Category: Marnett, L J | [[Category: Marnett, L J]] | ||
[[Category: Musee, J | [[Category: Musee, J]] | ||
[[Category: Oates, J A | [[Category: Oates, J A]] | ||
[[Category: Prusakiewicz, J J | [[Category: Prusakiewicz, J J]] | ||
[[Category: Scheib, J | [[Category: Scheib, J]] | ||
[[Category: Flurbiprofen]] | [[Category: Flurbiprofen]] | ||
[[Category: Oxidoreductase-oxidoreductase inhibitor complex]] | [[Category: Oxidoreductase-oxidoreductase inhibitor complex]] | ||
Revision as of 11:43, 18 December 2014
Structure of (R)-flurbiprofen bound to mCOX-2Structure of (R)-flurbiprofen bound to mCOX-2
Structural highlights
Publication Abstract from PubMedCyclooxygenase-2 (COX-2) catalyzes the oxygenation of arachidonic acid and the endocannabinoids 2-arachidonoylglycerol and arachidonoylethanolamide. Evaluation of a series of COX-2 inhibitors revealed that many weak competitive inhibitors of arachidonic acid oxygenation are potent inhibitors of endocannabinoid oxygenation. (R) enantiomers of ibuprofen, naproxen and flurbiprofen, which are considered to be inactive as COX-2 inhibitors, are potent 'substrate-selective inhibitors' of endocannabinoid oxygenation. Crystal structures of the COX-2-(R)-naproxen and COX-2-(R)-flurbiprofen complexes verified this unexpected binding and defined the orientation of the (R) enantiomers relative to (S) enantiomers. (R)-Profens selectively inhibited endocannabinoid oxygenation by lipopolysaccharide-stimulated dorsal root ganglion (DRG) cells. Substrate-selective inhibition provides new tools for investigating the role of COX-2 in endocannabinoid oxygenation and a possible explanation for the ability of (R)-profens to maintain endocannabinoid tone in models of neuropathic pain. (R)-Profens are substrate-selective inhibitors of endocannabinoid oxygenation by COX-2.,Duggan KC, Hermanson DJ, Musee J, Prusakiewicz JJ, Scheib JL, Carter BD, Banerjee S, Oates JA, Marnett LJ Nat Chem Biol. 2011 Nov;7(11):803-9. PMID:22053353[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences |
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