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4ph9

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The structure of Ibuprofen bound to cyclooxygenase-2

Structural highlights

4ph9 is a 2 chain structure with sequence from Mus musculus. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 1.81Å
Ligands:	, , , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

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.^[1] ^[2] ^[3] ^[4]

Publication Abstract from PubMed

The cyclooxygenases (COX-1 and COX-2) catalyze the rate-limiting step in the biosynthesis of prostaglandins, and are the pharmacological targets of non-steroidal anti-inflammatory drugs (NSAIDs) and COX-2 selective inhibitors (coxibs). Ibuprofen (IBP) is one of the most commonly available over-the-counter pharmaceuticals in the world. The anti-inflammatory and analgesic properties of IBP are thought to arise from inhibition of COX-2 rather than COX-1. While an X-ray crystal structure of IBP bound to COX-1 has been solved, no such structure exists for the cognate isoform COX-2. We have determined the crystal structure of muCOX-2 with a racemic mixture of (R/S)-IBP. Our structure reveals that only the S-isomer of IBP was bound, indicating that the S-isomer possesses higher affinity for COX-2 than the R-isomer. Mutational analysis of Arg-120 and Tyr-355 at the entrance of the cyclooxygenase channel confirmed their role in binding and inhibition of COX-2 by IBP. Our results provide the first atomic level detail of the interaction between IBP and COX-2.

The structure of ibuprofen bound to cyclooxygenase-2.,Orlando BJ, Lucido MJ, Malkowski MG J Struct Biol. 2014 Nov 25. pii: S1047-8477(14)00243-3. doi:, 10.1016/j.jsb.2014.11.005. PMID:25463020^[5]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Rowlinson SW, Kiefer JR, Prusakiewicz JJ, Pawlitz JL, Kozak KR, Kalgutkar AS, Stallings WC, Kurumbail RG, Marnett LJ. A novel mechanism of cyclooxygenase-2 inhibition involving interactions with Ser-530 and Tyr-385. J Biol Chem. 2003 Nov 14;278(46):45763-9. Epub 2003 Aug 18. PMID:12925531 doi:http://dx.doi.org/10.1074/jbc.M305481200
↑ Vecchio AJ, Simmons DM, Malkowski MG. Structural basis of fatty acid substrate binding to cyclooxygenase-2. J Biol Chem. 2010 Jul 16;285(29):22152-63. Epub 2010 May 12. PMID:20463020 doi:10.1074/jbc.M110.119867
↑ Duggan KC, Walters MJ, Musee J, Harp JM, Kiefer JR, Oates JA, Marnett LJ. Molecular basis for cyclooxygenase inhibition by the non-steroidal anti-inflammatory drug naproxen. J Biol Chem. 2010 Nov 5;285(45):34950-9. Epub 2010 Sep 1. PMID:20810665 doi:10.1074/jbc.M110.162982
↑ Vecchio AJ, Malkowski MG. The structural basis of endocannabinoid oxygenation by cyclooxygenase-2. J Biol Chem. 2011 Jun 10;286(23):20736-45. Epub 2011 Apr 13. PMID:21489986 doi:10.1074/jbc.M111.230367
↑ Orlando BJ, Lucido MJ, Malkowski MG. The structure of ibuprofen bound to cyclooxygenase-2. J Struct Biol. 2014 Nov 25. pii: S1047-8477(14)00243-3. doi:, 10.1016/j.jsb.2014.11.005. PMID:25463020 doi:http://dx.doi.org/10.1016/j.jsb.2014.11.005

1 Structural highlights
2 Function
3 Publication Abstract from PubMed
4 See Also
5 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/4ph9"

Categories: Large Structures | Mus musculus | Lucido MJ | Malkowski MG | Orlando BJ

@@ Line 1: / Line 1: @@
 ==The structure of Ibuprofen bound to cyclooxygenase-2==
-<StructureSection load='4ph9' size='340' side='right' caption='[[4ph9]], [[Resolution|resolution]] 1.81&Aring;' scene=''>
+<StructureSection load='4ph9' size='340' side='right'caption='[[4ph9]], [[Resolution|resolution]] 1.81&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[4ph9]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4PH9 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4PH9 FirstGlance]. <br>
+<table><tr><td colspan='2'>[[4ph9]] is a 2 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=4PH9 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4PH9 FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=AKR:ACRYLIC+ACID'>AKR</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=IBP:IBUPROFEN'>IBP</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 1.81&#8491;</td></tr>
-<tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[3qmo|3qmo]], [[1eqg|1eqg]], [[3hs5|3hs5]], [[3nt1|3nt1]]</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AKR:ACRYLIC+ACID'>AKR</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=IBP:IBUPROFEN'>IBP</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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'>[https://proteopedia.org/fgij/fg.htm?mol=4ph9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ph9 OCA], [https://pdbe.org/4ph9 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4ph9 RCSB], [https://www.ebi.ac.uk/pdbsum/4ph9 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4ph9 ProSAT]</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=4ph9 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4ph9 OCA], [http://www.rcsb.org/pdb/explore.do?structureId=4ph9 RCSB], [http://www.ebi.ac.uk/pdbsum/4ph9 PDBsum]</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 ==
@@ Line 16: / Line 18: @@
 From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 </div>
+<div class="pdbe-citations 4ph9" style="background-color:#fffaf0;"></div>
+==See Also==
+*[[Cyclooxygenase 3D structures|Cyclooxygenase 3D structures]]
 == References ==
 <references/>
 __TOC__
 </StructureSection>
-[[Category: Prostaglandin-endoperoxide synthase]]
+[[Category: Large Structures]]
-[[Category: Lucido, M J]]
+[[Category: Mus musculus]]
-[[Category: Malkowski, M G]]
+[[Category: Lucido MJ]]
-[[Category: Orlando, B J]]
+[[Category: Malkowski MG]]
-[[Category: Cox]]
+[[Category: Orlando BJ]]
-[[Category: Cox-2]]
-[[Category: Cyclooxygenase]]
-[[Category: Ibuprofen]]
-[[Category: Membrane protein]]
-[[Category: Monotopic]]
-[[Category: Nsaid]]
-[[Category: Oxidoreductase]]
-[[Category: Prostaglandin]]

4ph9

From Proteopedia

Current revision

The structure of Ibuprofen bound to cyclooxygenase-2

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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