6v3r: Difference between revisions
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<StructureSection load='6v3r' size='340' side='right'caption='[[6v3r]], [[Resolution|resolution]] 2.66Å' scene=''> | <StructureSection load='6v3r' size='340' side='right'caption='[[6v3r]], [[Resolution|resolution]] 2.66Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[6v3r]] is a 4 chain structure with sequence from [ | <table><tr><td colspan='2'>[[6v3r]] 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=6V3R OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6V3R FirstGlance]. <br> | ||
</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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=Y8A:9-[(4-chlorophenyl)methyl]-6-methoxy-1-methyl-4,9-dihydro-3H-beta-carboline'>Y8A</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]] 2.66Å</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=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=Y8A:9-[(4-chlorophenyl)methyl]-6-methoxy-1-methyl-4,9-dihydro-3H-beta-carboline'>Y8A</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=6v3r FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v3r OCA], [https://pdbe.org/6v3r PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6v3r RCSB], [https://www.ebi.ac.uk/pdbsum/6v3r PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6v3r 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 == | ||
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</StructureSection> | </StructureSection> | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: | [[Category: Mus musculus]] | ||
[[Category: Banerjee S]] | |||
[[Category: Banerjee | [[Category: Marnett LJ]] | ||
[[Category: Marnett | [[Category: Uddin MJ]] | ||
[[Category: Uddin | [[Category: Xu S]] | ||
[[Category: Xu | |||
Latest revision as of 11:03, 11 October 2023
Crystal structure of murine cycloxygenase in complex with a harmaline analog, 4,9-dihydro-3H-pyrido[3,4-b]indoleCrystal structure of murine cycloxygenase in complex with a harmaline analog, 4,9-dihydro-3H-pyrido[3,4-b]indole
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 PubMedWe report the design, synthesis, and evaluation of a series of harmaline analogs as selective inhibitors of 2-arachidonylglycerol (2-AG) oxygenation over arachidonic acid (AA) oxygenation by purified cyclooxygenase-2 (COX-2). A fused tricyclic harmaline analog containing a CH3O substituent at C-6 and a CH3 group at the C-1 position of 4,9-dihydro-3H-pyrido[3,4-b]indole (compound 3) was the best substrate-selective COX-2 inhibitor of those evaluated, exhibiting a 2AG-selective COX-2 inhibitory IC50 of 0.022 muM as compared to >1 muM for AA. The 2.66 A resolution crystal complex of COX-2 with compound 3 revealed that this series of tricyclic indoles binds in the cyclooxygenase channel by flipping the side chain of L531 toward the dimer interface. This novel tricyclic indole series provides the foundation for the development of promising substrate-selective molecules capable of increasing endocannabinoid (EC) levels in the brain to offer new treatments for a variety of diseases, from pain and inflammation to stress and anxiety disorders. Harmaline Analogs as Substrate-Selective Cyclooxygenase-2 Inhibitors.,Uddin MJ, Xu S, Crews BC, Aleem AM, Ghebreselasie K, Banerjee S, Marnett LJ ACS Med Chem Lett. 2020 Feb 14;11(10):1881-1885. doi:, 10.1021/acsmedchemlett.9b00555. eCollection 2020 Oct 8. PMID:33062168[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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