4z0l
From Proteopedia
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==The murine cyclooxygenase-2 complexed with a nido-dicarbaborate-containing indomethacin derivative== | ==The murine cyclooxygenase-2 complexed with a nido-dicarbaborate-containing indomethacin derivative== | ||
| - | <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. 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 [ | + | <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><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.29Å</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='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | + | <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> |
</table> | </table> | ||
== Function == | == 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 == | ||
| + | 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. | ||
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| + | 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<ref>PMID:26088701</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 4z0l" style="background-color:#fffaf0;"></div> | ||
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| + | ==See Also== | ||
| + | *[[Cyclooxygenase 3D structures|Cyclooxygenase 3D structures]] | ||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
| - | [[Category: | + | [[Category: Large Structures]] |
| - | [[Category: Banerjee | + | [[Category: Mus musculus]] |
| - | [[Category: Hey-Hawkins | + | [[Category: Banerjee S]] |
| - | [[Category: Marnett | + | [[Category: Hey-Hawkins E]] |
| - | [[Category: Neumann | + | [[Category: Marnett LJ]] |
| - | [[Category: Xu | + | [[Category: Neumann W]] |
| - | + | [[Category: Xu S]] | |
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Current revision
The murine cyclooxygenase-2 complexed with a nido-dicarbaborate-containing indomethacin derivative
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