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{{STRUCTURE_3qmo| PDB=3qmo | SCENE= }}
==X-ray crystal structure of NS-398 bound to the cyclooxygenase channel of cyclooxygenase-2==
===X-ray crystal structure of NS-398 bound to the cyclooxygenase channel of cyclooxygenase-2===
<StructureSection load='3qmo' size='340' side='right' caption='[[3qmo]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
{{ABSTRACT_PUBMED_21843643}}
== Structural highlights ==
<table><tr><td colspan='2'>[[3qmo]] is a 2 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=3QMO OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QMO FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=NS4:N-[2-(CYCLOHEXYLOXY)-4-NITROPHENYL]METHANESULFONAMIDE'>NS4</scene>, <scene name='pdbligand=NDG:2-(ACETYLAMINO)-2-DEOXY-A-D-GLUCOPYRANOSE'>NDG</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3hs5|3hs5]], [[3hs6|3hs6]], [[3hs7|3hs7]], [[3ln1|3ln1]], [[6cox|6cox]], [[3nt1|3nt1]]</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=3qmo FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qmo OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qmo RCSB], [http://www.ebi.ac.uk/pdbsum/3qmo PDBsum]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The cyclooxygenases (COX-1 and COX-2) are membrane-associated, heme-containing homodimers that generate prostaglandin H(2) from arachidonic acid (AA) in the committed step of prostaglandin biogenesis and are the targets for nonsteroidal anti-inflammatory drugs (NSAIDs). N-(2-cyclohexyloxy-4-nitrophenyl) methanesulfonamide (NS-398) was the first in a series of isoform-selective drugs designed to preferentially inhibit COX-2, with the aim of ameliorating many of the toxic gastrointestinal side effects caused by conventional NSAID inhibition. We determined the X-ray crystal structure of murine COX-2 in complex with NS-398 utilizing synchrotron radiation to 3.0A resolution. NS-398 binds in the cyclooxygenase channel in a conformation that is different than that observed for other COX-2-selective inhibitors, such as celecoxib, with no discernible penetration into the side pocket formed in COX-2 by the isoform-specific substitutions of I434V, H513R, and I523V. Instead, the methanesulfonamide moiety of NS-398 interacts with the side chain of Arg-120 at the opening of the cyclooxygenase channel, similar to that observed for acidic, nonselective NSAIDs such as indomethacin and flurbiprofen. Our structure validates inhibitor studies that identified Arg-120 as a molecular determinant for time-dependent inhibition of COX-2 by NS-398.


==About this Structure==
The structure of NS-398 bound to cyclooxygenase-2.,Vecchio AJ, Malkowski MG J Struct Biol. 2011 Aug 6. PMID:21843643<ref>PMID:21843643</ref>
[[3qmo]] is a 2 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=3QMO OCA].
 
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>


==See Also==
==See Also==
*[[Cyclooxygenase|Cyclooxygenase]]
*[[Cyclooxygenase|Cyclooxygenase]]
 
== References ==
==Reference==
<references/>
<ref group="xtra">PMID:021843643</ref><references group="xtra"/>
__TOC__
</StructureSection>
[[Category: Mus musculus]]
[[Category: Mus musculus]]
[[Category: Prostaglandin-endoperoxide synthase]]
[[Category: Prostaglandin-endoperoxide synthase]]
[[Category: Malkowski, M G.]]
[[Category: Malkowski, M G]]
[[Category: Vecchio, A J.]]
[[Category: Vecchio, A J]]
[[Category: Biological dimer]]
[[Category: Biological dimer]]
[[Category: Dimer]]
[[Category: Dimer]]
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