4rs0: Difference between revisions
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==Crystal Structure of Murine H90W Cyclooxygenase-2 Complexed with S-ibuprofen== | ==Crystal Structure of Murine H90W Cyclooxygenase-2 Complexed with S-ibuprofen== | ||
<StructureSection load='4rs0' size='340' side='right' caption='[[4rs0]], [[Resolution|resolution]] 2.81Å' scene=''> | <StructureSection load='4rs0' size='340' side='right'caption='[[4rs0]], [[Resolution|resolution]] 2.81Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[4rs0]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4RS0 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[4rs0]] is a 1 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=4RS0 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4RS0 FirstGlance]. <br> | ||
</td></tr><tr id=' | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.807Å</td></tr> | ||
<tr id=' | <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=IBP:IBUPROFEN'>IBP</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=4rs0 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4rs0 OCA], [https://pdbe.org/4rs0 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4rs0 RCSB], [https://www.ebi.ac.uk/pdbsum/4rs0 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4rs0 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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</div> | </div> | ||
<div class="pdbe-citations 4rs0" style="background-color:#fffaf0;"></div> | <div class="pdbe-citations 4rs0" 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: | [[Category: Banerjee S]] | ||
[[Category: Blobaum AL]] | |||
[[Category: Marnett LJ]] | |||
[[Category: | [[Category: Xu S]] | ||
[[Category: | |||
[[Category: | |||
Latest revision as of 20:54, 20 September 2023
Crystal Structure of Murine H90W Cyclooxygenase-2 Complexed with S-ibuprofenCrystal Structure of Murine H90W Cyclooxygenase-2 Complexed with S-ibuprofen
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 PubMedCyclooxygenase enzymes (COX-1 and COX-2) catalyze the conversion of arachidonic acid (AA) to prostaglandin (PG)G2. The inhibitory activity of rapid, reversible COX inhibitors (ibuprofen, naproxen, mefenamic acid, and lumiracoxib) demonstrated a significant increase in potency and time-dependence of inhibition against double tryptophan mCOX-2 mutants at the 89/90 and 89/119 positions. In contrast, the slow, time-dependent COX inhibitors (diclofenac, indomethacin, and flurbiprofen) were unaffected by those mutations. Further mutagenesis studies suggested that mutation at position 89 was principally responsible for the changes in inhibitory potency of rapid, reversible inhibitors, while mutation at position 90 may exert some effect on the potency of COX-2-selective diarylheterocycle inhibitors; no effect was observed with mutation at position 119. Several crystal structures with or without NSAIDs indicated that placement of a bulky residue at position 89 caused a closure of a gap at the lobby, and alteration of histidine to tryptophan at position 90 changed the electrostatic profile of the side-pocket of COX-2. Thus, these two residues, especially Val-89 at the lobby region, are crucial for the entrance and exit of some NSAIDs from the COX active site. Action at a Distance: Mutations of Peripheral Residues Transform Rapid Reversible Inhibitors to Slow, Tight Binders of Cyclooxygenase-2.,Blobaum AL, Xu S, Rowlinson SW, Duggan KC, Banerjee S, Kudalkar SN, Birmingham WR, Ghebreselasie K, Marnett LJ J Biol Chem. 2015 Mar 30. pii: jbc.M114.635987. PMID:25825493[5] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See AlsoReferences
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