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'''Unreleased structure'''


The entry 5fdq is ON HOLD
==Murine COX-2 S530T mutant==
<StructureSection load='5fdq' size='340' side='right' caption='[[5fdq]], [[Resolution|resolution]] 1.90&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[5fdq]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5FDQ OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5FDQ FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=60A:2-[(2~{R})-2-(HYDROXYMETHYLOXY)PROPOXY]ETHANOL'>60A</scene>, <scene name='pdbligand=AKR:ACRYLIC+ACID'>AKR</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=COH:PROTOPORPHYRIN+IX+CONTAINING+CO'>COH</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[5f1a|5f1a]], [[5f19|5f19]]</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=5fdq FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5fdq OCA], [http://pdbe.org/5fdq PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5fdq RCSB], [http://www.ebi.ac.uk/pdbsum/5fdq 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> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Aspirin and other nonsteroidal anti-inflammatory drugs target the cyclooxygenase enzymes (COX-1 and COX-2) to block the formation of prostaglandins. Aspirin is unique in that it covalently modifies each enzyme by acetylating Ser-530 within the cyclooxygenase active site. Acetylation of COX-1 leads to complete loss of activity, while acetylation of COX-2 results in the generation of the monooxygenated product 15(R)-hydroxyeicosatetraenoic acid (15R-HETE). Ser-530 has also been shown to influence the stereochemistry for the addition of oxygen to the prostaglandin product. We determined the crystal structures of S530T murine (mu) COX-2, aspirin-acetylated human (hu) COX-2, and huCOX-2 in complex with salicylate to 1.9, 2.0, and 2.4 A, respectively. The structures reveal that (1) the acetylated Ser-530 completely blocks access to the hydrophobic groove, (2) the observed binding pose of salicylate is reflective of the enzyme-inhibitor complex prior to acetylation, and (3) the observed Thr-530 rotamer in the S530T muCOX-2 crystal structure does not impede access to the hydrophobic groove. On the basis of these structural observations, along with functional analysis of the S530T/G533V double mutant, we propose a working hypothesis for the generation of 15R-HETE by aspirin-acetylated COX-2. We also observe differential acetylation of COX-2 purified in various detergent systems and nanodiscs, indicating that detergent and lipid binding within the membrane-binding domain of the enzyme alters the rate of the acetylation reaction in vitro.


Authors: Lucido, M.J., Orlando, B.J., Malkowski, M.G.
Crystal Structure of Aspirin-Acetylated Human Cyclooxygenase-2: Insight into the Formation of Products with Reversed Stereochemistry.,Lucido MJ, Orlando BJ, Vecchio AJ, Malkowski MG Biochemistry. 2016 Mar 1;55(8):1226-38. doi: 10.1021/acs.biochem.5b01378. Epub, 2016 Feb 19. PMID:26859324<ref>PMID:26859324</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
[[Category: Lucido, M.J]]
<div class="pdbe-citations 5fdq" style="background-color:#fffaf0;"></div>
[[Category: Orlando, B.J]]
== References ==
[[Category: Malkowski, M.G]]
<references/>
__TOC__
</StructureSection>
[[Category: Prostaglandin-endoperoxide synthase]]
[[Category: Lucido, M J]]
[[Category: Malkowski, M G]]
[[Category: Orlando, B J]]
[[Category: Cox-2]]
[[Category: Cyclooxygenase]]
[[Category: Cyxlooxygenase-2]]
[[Category: Monotopic]]
[[Category: Oxidoreductase-inhibitor complex]]
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