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==CYCLOOXYGENASE-2 (PROSTAGLANDIN SYNTHASE-2) COMPLEXED WITH A NON-SELECTIVE INHIBITOR, FLURBIPROFEN==
==CYCLOOXYGENASE-2 (PROSTAGLANDIN SYNTHASE-2) COMPLEXED WITH A NON-SELECTIVE INHIBITOR, FLURBIPROFEN==
<StructureSection load='3pgh' size='340' side='right' caption='[[3pgh]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
<StructureSection load='3pgh' size='340' side='right'caption='[[3pgh]], [[Resolution|resolution]] 2.50&Aring;' scene=''>
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[3pgh]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3PGH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3PGH FirstGlance]. <br>
<table><tr><td colspan='2'>[[3pgh]] 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=3PGH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3PGH FirstGlance]. <br>
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=FLP:FLURBIPROFEN'>FLP</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</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]] 2.5&#8491;</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='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FLP:FLURBIPROFEN'>FLP</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3pgh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pgh OCA], [http://pdbe.org/3pgh PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3pgh RCSB], [http://www.ebi.ac.uk/pdbsum/3pgh PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3pgh ProSAT]</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=3pgh FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3pgh OCA], [https://pdbe.org/3pgh PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3pgh RCSB], [https://www.ebi.ac.uk/pdbsum/3pgh PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3pgh ProSAT]</span></td></tr>
</table>
</table>
== Function ==
== 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>
[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>  
== Evolutionary Conservation ==
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
[[Image:Consurf_key_small.gif|200px|right]]
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   <jmolCheckbox>
   <jmolCheckbox>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pg/3pgh_consurf.spt"</scriptWhenChecked>
     <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/pg/3pgh_consurf.spt"</scriptWhenChecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
     <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview03.spt</scriptWhenUnchecked>
     <text>to colour the structure by Evolutionary Conservation</text>
     <text>to colour the structure by Evolutionary Conservation</text>
   </jmolCheckbox>
   </jmolCheckbox>
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==See Also==
==See Also==
*[[Cyclooxygenase|Cyclooxygenase]]
*[[Cyclooxygenase 3D structures|Cyclooxygenase 3D structures]]
== References ==
== References ==
<references/>
<references/>
__TOC__
__TOC__
</StructureSection>
</StructureSection>
[[Category: Lk3 transgenic mice]]
[[Category: Large Structures]]
[[Category: Prostaglandin-endoperoxide synthase]]
[[Category: Mus musculus]]
[[Category: Kurumbail, R]]
[[Category: Kurumbail R]]
[[Category: Stallings, W]]
[[Category: Stallings W]]
[[Category: Arthritis]]
[[Category: Cyclooxygenase]]
[[Category: Dioxygenase]]
[[Category: Inflammation]]
[[Category: Nonsteroidal antiinflammatory drug]]
[[Category: Oxidoreductase]]
[[Category: Peroxidase]]
[[Category: Prostaglandin]]
[[Category: Prostaglandin synthase]]

Latest revision as of 05:16, 21 November 2024

CYCLOOXYGENASE-2 (PROSTAGLANDIN SYNTHASE-2) COMPLEXED WITH A NON-SELECTIVE INHIBITOR, FLURBIPROFENCYCLOOXYGENASE-2 (PROSTAGLANDIN SYNTHASE-2) COMPLEXED WITH A NON-SELECTIVE INHIBITOR, FLURBIPROFEN

Structural highlights

3pgh is a 4 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 2.5Å
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]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Prostaglandins and glucocorticoids are potent mediators of inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) exert their effects by inhibition of prostaglandin production. The pharmacological target of NSAIDs is cyclooxygenase (COX, also known as PGH synthase), which catalyses the first committed step in arachidonic-acid metabolism. Two isoforms of the membrane protein COX are known: COX-1, which is constitutively expressed in most tissues, is responsible for the physiological production of prostaglandins; and COX-2, which is induced by cytokines, mitogens and endotoxins in inflammatory cells, is responsible for the elevated production of prostaglandins during inflammation. The structure of ovine COX-1 complexed with several NSAIDs has been determined. Here we report the structures of unliganded murine COX-2 and complexes with flurbiprofen, indomethacin and SC-558, a selective COX-2 inhibitor, determined at 3.0 to 2.5 A resolution. These structures explain the structural basis for the selective inhibition of COX-2, and demonstrate some of the conformational changes associated with time-dependent inhibition.

Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents.,Kurumbail RG, Stevens AM, Gierse JK, McDonald JJ, Stegeman RA, Pak JY, Gildehaus D, Miyashiro JM, Penning TD, Seibert K, Isakson PC, Stallings WC Nature. 1996 Dec 19-26;384(6610):644-8. PMID:8967954[5]

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

See Also

References

  1. ↑ 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
  2. ↑ 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
  3. ↑ 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
  4. ↑ 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
  5. ↑ Kurumbail RG, Stevens AM, Gierse JK, McDonald JJ, Stegeman RA, Pak JY, Gildehaus D, Miyashiro JM, Penning TD, Seibert K, Isakson PC, Stallings WC. Structural basis for selective inhibition of cyclooxygenase-2 by anti-inflammatory agents. Nature. 1996 Dec 19-26;384(6610):644-8. PMID:8967954 doi:http://dx.doi.org/10.1038/384644a0

3pgh, resolution 2.50Å

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