4oty: Difference between revisions
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==Crystal structure of lumiracoxib bound to the apo-mouse-cyclooxygenase-2== | |||
<StructureSection load='4oty' size='340' side='right' caption='[[4oty]], [[Resolution|resolution]] 2.35Å' scene=''> | |||
{ | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4oty]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. This structure supersedes the now removed PDB entry [http://oca.weizmann.ac.il/oca-bin/send-pdb?obs=1&id=4llz 4llz]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4OTY OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4OTY FirstGlance]. <br> | |||
==Function== | </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=LUR:{2-[(2-CHLORO-6-FLUOROPHENYL)AMINO]-5-METHYLPHENYL}ACETIC+ACID'>LUR</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 LK3 transgenic mice])</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=4oty FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4oty OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4oty RCSB], [http://www.ebi.ac.uk/pdbsum/4oty PDBsum]</span></td></tr> | |||
</table> | |||
== Function == | |||
[[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> | [[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> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
Lumiracoxib is a substrate-selective inhibitor of endocannabinoid oxygenation by cyclooxygenase-2 (COX-2). We assayed a series of lumiracoxib derivatives to identify the structural determinants of substrate-selective inhibition. The hydrogen-bonding potential of the substituents at the ortho positions of the aniline ring dictated the potency and substrate selectivity of the inhibitors. The presence of a 5'-methyl group on the phenylacetic acid ring increased the potency of molecules with a single ortho substituent. Des-fluorolumiracoxib (2) was the most potent and selective inhibitor of endocannabinoid oxygenation. The positioning of critical substituents in the binding site was identified from a 2.35A crystal structure of lumiracoxib bound to COX-2. | |||
Exploring the molecular determinants of substrate-selective inhibition of cyclooxygenase-2 by lumiracoxib.,Windsor MA, Valk PL, Xu S, Banerjee S, Marnett LJ Bioorg Med Chem Lett. 2013 Nov 1;23(21):5860-5864. doi:, 10.1016/j.bmcl.2013.08.097. Epub 2013 Sep 6. PMID:24060487<ref>PMID:24060487</ref> | |||
== | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
</div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Lk3 transgenic mice]] | |||
[[Category: Prostaglandin-endoperoxide synthase]] | [[Category: Prostaglandin-endoperoxide synthase]] | ||
[[Category: Banerjee, S | [[Category: Banerjee, S]] | ||
[[Category: Marnett, L J | [[Category: Marnett, L J]] | ||
[[Category: Windsor, M A | [[Category: Windsor, M A]] | ||
[[Category: Xu, S | [[Category: Xu, S]] | ||
[[Category: Drug complex]] | [[Category: Drug complex]] | ||
[[Category: Glycosylation]] | [[Category: Glycosylation]] | ||
