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4z0l

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The murine cyclooxygenase-2 complexed with a nido-dicarbaborate-containing indomethacin derivative

Structural highlights

4z0l 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 2.29Å
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

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.

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

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/4z0l"

@@ Line 1: / Line 1: @@
 ==The murine cyclooxygenase-2 complexed with a nido-dicarbaborate-containing indomethacin derivative==
-<StructureSection load='4z0l' size='340' side='right' caption='[[4z0l]], [[Resolution|resolution]] 2.29&Aring;' scene=''>
+<StructureSection load='4z0l' size='340' side='right'caption='[[4z0l]], [[Resolution|resolution]] 2.29&Aring;' scene=''>
 == 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 [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='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.29&#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=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'>[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]</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=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>
 == 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;">
 == Publication Abstract from PubMed ==
@@ Line 18: / Line 19: @@
 </div>
 <div class="pdbe-citations 4z0l" 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: Banerjee, S]]
+[[Category: Mus musculus]]
-[[Category: Hey-Hawkins, E]]
+[[Category: Banerjee S]]
-[[Category: Marnett, L J]]
+[[Category: Hey-Hawkins E]]
-[[Category: Neumann, W]]
+[[Category: Marnett LJ]]
-[[Category: Xu, S]]
+[[Category: Neumann W]]
-[[Category: Cyclooxygenase]]
+[[Category: Xu S]]
-[[Category: Indomethacin]]
-[[Category: Oxidoreductase-oxidoreductase inhibitor complex]]

4z0l

From Proteopedia

Current revision

The murine cyclooxygenase-2 complexed with a nido-dicarbaborate-containing indomethacin derivative

Structural highlights

Function

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

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