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| | <StructureSection load='4z0l' size='340' side='right'caption='[[4z0l]], [[Resolution|resolution]] 2.29Å' scene=''> | | <StructureSection load='4z0l' size='340' side='right'caption='[[4z0l]], [[Resolution|resolution]] 2.29Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4z0l]] 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=4Z0L OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4Z0L FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4z0l]] 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=4Z0L OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4Z0L FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=4LA:(R)-7-{[5-METHOXY-2-METHYL-3-(METHOXYCARBONYLMETHYL)-1H-INDOLYL]CARBONYL}-7,8-DICARBA-NIDO-DODECA-HYDROUNDECABORATE'>4LA</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=N1B:(S)-7-{[5-METHOXY-2-METHYL-3-(METHOXYCARBONYLMETHYL)-1H-INDOLYL]CARBONYL}-7,8-DICARBA-NIDO-DODECA-HYDROUNDECABORATE'>N1B</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=4LA:(R)-7-{[5-METHOXY-2-METHYL-3-(METHOXYCARBONYLMETHYL)-1H-INDOLYL]CARBONYL}-7,8-DICARBA-NIDO-DODECA-HYDROUNDECABORATE'>4LA</scene>, <scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=N1B:(S)-7-{[5-METHOXY-2-METHYL-3-(METHOXYCARBONYLMETHYL)-1H-INDOLYL]CARBONYL}-7,8-DICARBA-NIDO-DODECA-HYDROUNDECABORATE'>N1B</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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 LK3 transgenic mice])</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=4z0l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z0l OCA], [https://pdbe.org/4z0l PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4z0l RCSB], [https://www.ebi.ac.uk/pdbsum/4z0l PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4z0l ProSAT]</span></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=4z0l FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4z0l OCA], [http://pdbe.org/4z0l PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4z0l RCSB], [http://www.ebi.ac.uk/pdbsum/4z0l PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4z0l 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> |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | </StructureSection> | | </StructureSection> |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Prostaglandin-endoperoxide synthase]]
| + | [[Category: Banerjee S]] |
| - | [[Category: Banerjee, S]] | + | [[Category: Hey-Hawkins E]] |
| - | [[Category: Hey-Hawkins, E]] | + | [[Category: Marnett LJ]] |
| - | [[Category: Marnett, L J]] | + | [[Category: Neumann W]] |
| - | [[Category: Neumann, W]] | + | [[Category: Xu S]] |
| - | [[Category: Xu, S]] | + | |
| - | [[Category: Cyclooxygenase]]
| + | |
| - | [[Category: Indomethacin]]
| + | |
| - | [[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
| + | |
| Structural highlights
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
Carbaboranes are increasingly studied as pharmacophores, particularly as replacements for aromatic systems. However, especially ortho-carbaborane is prone to degradation of the cluster, which hampers biological application. This study demonstrates that deboronation of the cluster may not only lead to a more active analogue, but can also improve the solubility and stability of a carbaborane-containing inhibitor. Notably, introduction of a nido-dicarbaborate cluster into the cyclooxygenase (COX) inhibitor indomethacin results in remarkably increased inhibitory potency and selectivity for COX-2 relative to the respective phenyl analogue. The first crystal structure of a carbaborane-containing inhibitor bound to COX-2 further reveals a novel binding mode for the inhibitor that is strikingly different from that of indomethacin. These results indicate that nido-dicarbaborate is a promising pharmacophore that exhibits properties which are also highly beneficial for its introduction into other inhibitor classes.
nido-Dicarbaborate Induces Potent and Selective Inhibition of Cyclooxygenase-2.,Neumann W, Xu S, Sarosi MB, Scholz MS, Crews BC, Ghebreselasie K, Banerjee S, Marnett LJ, Hey-Hawkins HC ChemMedChem. 2015 Jun 18. doi: 10.1002/cmdc.201500199. PMID:26088701[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
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
- ↑ Neumann W, Xu S, Sarosi MB, Scholz MS, Crews BC, Ghebreselasie K, Banerjee S, Marnett LJ, Hey-Hawkins HC. nido-Dicarbaborate Induces Potent and Selective Inhibition of Cyclooxygenase-2. ChemMedChem. 2015 Jun 18. doi: 10.1002/cmdc.201500199. PMID:26088701 doi:http://dx.doi.org/10.1002/cmdc.201500199
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