4m10: Difference between revisions
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==Crystal Structure of Murine Cyclooxygenase-2 Complex with Isoxicam== | ==Crystal Structure of Murine Cyclooxygenase-2 Complex with Isoxicam== | ||
<StructureSection load='4m10' size='340' side='right' caption='[[4m10]], [[Resolution|resolution]] 2.01Å' scene=''> | <StructureSection load='4m10' size='340' side='right'caption='[[4m10]], [[Resolution|resolution]] 2.01Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4m10]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[4m10]] 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=4M10 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4M10 FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=ICD:4-HYDROXY-2-METHYL-N-(5-METHYL-1,2-OXAZOL-3-YL)-2H-1,2-BENZOTHIAZINE-3-CARBOXAMIDE+1,1-DIOXIDE'>ICD</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BOG:B-OCTYLGLUCOSIDE'>BOG</scene>, <scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=ICD:4-HYDROXY-2-METHYL-N-(5-METHYL-1,2-OXAZOL-3-YL)-2H-1,2-BENZOTHIAZINE-3-CARBOXAMIDE+1,1-DIOXIDE'>ICD</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'>[https://proteopedia.org/fgij/fg.htm?mol=4m10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4m10 OCA], [https://pdbe.org/4m10 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4m10 RCSB], [https://www.ebi.ac.uk/pdbsum/4m10 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4m10 ProSAT]</span></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | |||
</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;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
| Line 21: | Line 18: | ||
</div> | </div> | ||
<div class="pdbe-citations 4m10" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4m10" style="background-color:#fffaf0;"></div> | ||
==See Also== | |||
*[[Cyclooxygenase 3D structures|Cyclooxygenase 3D structures]] | |||
== References == | == References == | ||
<references/> | <references/> | ||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mus musculus]] | ||
[[Category: Banerjee | [[Category: Banerjee S]] | ||
[[Category: Ghebreelasie | [[Category: Ghebreelasie K]] | ||
[[Category: Hermanson | [[Category: Hermanson DJ]] | ||
[[Category: Marnett | [[Category: Marnett LJ]] | ||
[[Category: Xu | [[Category: Xu S]] | ||
Revision as of 13:46, 21 December 2022
Crystal Structure of Murine Cyclooxygenase-2 Complex with IsoxicamCrystal Structure of Murine Cyclooxygenase-2 Complex with Isoxicam
Structural highlights
FunctionPGH2_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 PubMedOxicams are widely used non-steroidal anti-inflammatory drugs (NSAIDs), but little is known about the molecular basis of the interaction with their target enzymes, the cyclooxygenases (COX). Isoxicam is a non-selective inhibitor of COX-1 and COX-2 whereas meloxicam displays some selectivity for COX-2. Here we report crystal complexes of COX-2 with isoxicam and meloxicam at 2.0 angstroms and 2.45 angstroms, respectively, and a crystal complex of COX-1 with meloxicam at 2.4 angstroms. These structures reveal that the oxicams bind to the active site of COX-2 using a binding pose not seen with other NSAIDs through two highly coordinated water molecules. The 4-hydroxyl group on the thiazine ring partners with Ser-530 via hydrogen bonding and the heteroatom of the carboxamide ring of the oxicam scaffold interacts with Tyr-385 and Ser-530 through a highly coordinated water molecule. The nitrogen atom of the thiazine and the oxygen atom of the carboxamide bind to Arg-120 and Tyr-355 via another highly ordered water molecule. The rotation of Leu-531 in the structure opens a novel-binding pocket, which is not utilized for the binding of other NSAIDs. In addition, a detailed study of meloxicam-COX-2 interactions revealed that mutation of Val-434 to Ile significantly reduces inhibition by meloxicam due to subtle changes around Phe-518, giving rise to the preferential inhibition of COX-2 over COX-1. Oxicams Bind in a Novel Mode to the Cyclooxygenase Active Site via a Two-water-mediated H-bonding Network.,Xu S, Hermanson DJ, Banerjee S, Ghebreselasie K, Clayton GM, Garavito RM, Marnett LJ J Biol Chem. 2014 Jan 14. PMID:24425867[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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