View source for 4rut


==crystal structure of murine cyclooxygenase-2 with 13-methyl-arachidonic Acid==
<StructureSection load='4rut' size='340' side='right'caption='[[4rut]], [[Resolution|resolution]] 2.16&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[4rut]] 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=4RUT OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RUT FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.16&#8491;</td></tr>
<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=LM8:(5Z,8Z,11Z,13S,14Z)-13-METHYLICOSA-5,8,11,14-TETRAENOIC+ACID'>LM8</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=4rut FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rut OCA], [https://pdbe.org/4rut PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rut RCSB], [https://www.ebi.ac.uk/pdbsum/4rut PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rut ProSAT]</span></td></tr>
</table>
== Function ==
[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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Cyclooxygenase-2 (COX-2) oxygenates arachidonic acid (AA) and the endocannabinoids 2-arachidonoylglycerol (2-AG) and arachidonylethanolamide to prostaglandins, prostaglandin glyceryl esters, and prostaglandin ethanolamides, respectively. A structural homodimer, COX-2 acts as a conformational heterodimer with a catalytic and an allosteric monomer. Prior studies have demonstrated substrate-selective negative allosteric regulation of 2-AG oxygenation. Here we describe AM-8138 (13(S)-methylarachidonic acid), a substrate-selective allosteric potentiator that augments 2-AG oxygenation by up to 3.5-fold with no effect on AA oxygenation. In the crystal structure of an AM-8138.COX-2 complex, AM-8138 adopts a conformation similar to the unproductive conformation of AA in the substrate binding site. Kinetic analysis suggests that binding of AM-8138 to the allosteric monomer of COX-2 increases 2-AG oxygenation by increasing kcat and preventing inhibitory binding of 2-AG. AM-8138 restored the activity of COX-2 mutants that exhibited very poor 2-AG oxygenating activity and increased the activity of COX-1 toward 2-AG. Competition of AM-8138 for the allosteric site prevented the inhibition of COX-2-dependent 2-AG oxygenation by substrate-selective inhibitors and blocked the inhibition of AA or 2-AG oxygenation by nonselective time-dependent inhibitors. AM-8138 selectively enhanced 2-AG oxygenation in intact RAW264.7 macrophage-like cells. Thus, AM-8138 is an important new tool compound for the exploration of allosteric modulation of COX enzymes and their role in endocannabinoid metabolism.

13-methylarachidonic Acid is a positive allosteric modulator of endocannabinoid oxygenation by cyclooxygenase.,Kudalkar SN, Nikas SP, Kingsley PJ, Xu S, Galligan JJ, Rouzer CA, Banerjee S, Ji L, Eno MR, Makriyannis A, Marnett LJ J Biol Chem. 2015 Mar 20;290(12):7897-909. doi: 10.1074/jbc.M114.634014. Epub, 2015 Feb 2. PMID:25648895<ref>PMID:25648895</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 4rut" style="background-color:#fffaf0;"></div>

==See Also==
*[[Cyclooxygenase 3D structures|Cyclooxygenase 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Mus musculus]]
[[Category: Banerjee S]]
[[Category: Kudalkar SN]]
[[Category: Makriyannis A]]
[[Category: Marnett LJ]]
[[Category: Nikas SP]]
[[Category: Xu S]]