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| | <StructureSection load='4o1z' size='340' side='right'caption='[[4o1z]], [[Resolution|resolution]] 2.40Å' scene=''> | | <StructureSection load='4o1z' size='340' side='right'caption='[[4o1z]], [[Resolution|resolution]] 2.40Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[4o1z]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Ovis_aries Ovis aries]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O1Z OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=4O1Z FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[4o1z]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Ovis_aries Ovis aries]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=4O1Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=4O1Z FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MXM:4-HYDROXY-2-METHYL-N-(5-METHYL-1,3-THIAZOL-2-YL)-2H-1,2-BENZOTHIAZINE-3-CARBOXAMIDE+1,1-DIOXIDE'>MXM</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> | + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=HEM:PROTOPORPHYRIN+IX+CONTAINING+FE'>HEM</scene>, <scene name='pdbligand=MXM:4-HYDROXY-2-METHYL-N-(5-METHYL-1,3-THIAZOL-2-YL)-2H-1,2-BENZOTHIAZINE-3-CARBOXAMIDE+1,1-DIOXIDE'>MXM</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[4m11|4m11]], [[1diy|1diy]], [[1q4g|1q4g]]</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=4o1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o1z OCA], [https://pdbe.org/4o1z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=4o1z RCSB], [https://www.ebi.ac.uk/pdbsum/4o1z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=4o1z ProSAT]</span></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='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=4o1z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=4o1z OCA], [http://pdbe.org/4o1z PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=4o1z RCSB], [http://www.ebi.ac.uk/pdbsum/4o1z PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=4o1z ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PGH1_SHEEP PGH1_SHEEP]] May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells. | + | [https://www.uniprot.org/uniprot/PGH1_SHEEP PGH1_SHEEP] May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells. |
| | <div style="background-color:#fffaf0;"> | | <div style="background-color:#fffaf0;"> |
| | == Publication Abstract from PubMed == | | == Publication Abstract from PubMed == |
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| | | | |
| | ==See Also== | | ==See Also== |
| - | *[[Cyclooxygenase|Cyclooxygenase]] | + | *[[Cyclooxygenase 3D structures|Cyclooxygenase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
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| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| | [[Category: Ovis aries]] | | [[Category: Ovis aries]] |
| - | [[Category: Prostaglandin-endoperoxide synthase]]
| + | [[Category: Banerjee S]] |
| - | [[Category: Banerjee, S]] | + | [[Category: Clayton GM]] |
| - | [[Category: Clayton, G M]] | + | [[Category: Garavito RM]] |
| - | [[Category: Garavito, R M]] | + | [[Category: Ghebreselasie K]] |
| - | [[Category: Ghebreselasie, K]] | + | [[Category: Hermanson DJ]] |
| - | [[Category: Hermanson, D J]] | + | [[Category: Marnett LJ]] |
| - | [[Category: Marnett, L J]] | + | [[Category: Xu S]] |
| - | [[Category: Xu, S]] | + | |
| - | [[Category: Dioxygenase]]
| + | |
| - | [[Category: Glycosylation]]
| + | |
| - | [[Category: Membrane]]
| + | |
| - | [[Category: Nsaid]]
| + | |
| - | [[Category: Oxidoreductase-oxidoreductase inhibitor complex]]
| + | |
| - | [[Category: Peroxidase]]
| + | |
| Structural highlights
Function
PGH1_SHEEP May play an important role in regulating or promoting cell proliferation in some normal and neoplastically transformed cells.
Publication Abstract from PubMed
Oxicams 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[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Xu S, Hermanson DJ, Banerjee S, Ghebreselasie K, Clayton GM, Garavito RM, Marnett LJ. Oxicams Bind in a Novel Mode to the Cyclooxygenase Active Site via a Two-water-mediated H-bonding Network. J Biol Chem. 2014 Jan 14. PMID:24425867 doi:http://dx.doi.org/10.1074/jbc.M113.517987
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