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| | ==THE 2.7 ANGSTROM RESOLUTION MODEL OF OVINE COX-1 COMPLEXED WITH ALCLOFENAC== | | ==THE 2.7 ANGSTROM RESOLUTION MODEL OF OVINE COX-1 COMPLEXED WITH ALCLOFENAC== |
| - | <StructureSection load='1ht8' size='340' side='right' caption='[[1ht8]], [[Resolution|resolution]] 2.69Å' scene=''> | + | <StructureSection load='1ht8' size='340' side='right'caption='[[1ht8]], [[Resolution|resolution]] 2.69Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[1ht8]] 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=1HT8 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1HT8 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[1ht8]] 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=1HT8 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=1HT8 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=34C:(3-CHLORO-4-PROPOXY-PHENYL)-ACETIC+ACID'>34C</scene>, <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></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]] 2.69Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[1eqh|1eqh]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=34C:(3-CHLORO-4-PROPOXY-PHENYL)-ACETIC+ACID'>34C</scene>, <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></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'>[https://proteopedia.org/fgij/fg.htm?mol=1ht8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ht8 OCA], [https://pdbe.org/1ht8 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=1ht8 RCSB], [https://www.ebi.ac.uk/pdbsum/1ht8 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=1ht8 ProSAT]</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=1ht8 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1ht8 OCA], [http://pdbe.org/1ht8 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=1ht8 RCSB], [http://www.ebi.ac.uk/pdbsum/1ht8 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=1ht8 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. |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | </div> | | </div> |
| | <div class="pdbe-citations 1ht8" style="background-color:#fffaf0;"></div> | | <div class="pdbe-citations 1ht8" style="background-color:#fffaf0;"></div> |
| | + | |
| | + | ==See Also== |
| | + | *[[Cyclooxygenase 3D structures|Cyclooxygenase 3D structures]] |
| | == References == | | == References == |
| | <references/> | | <references/> |
| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| | + | [[Category: Large Structures]] |
| | [[Category: Ovis aries]] | | [[Category: Ovis aries]] |
| - | [[Category: Prostaglandin-endoperoxide synthase]]
| + | [[Category: Gupta K]] |
| - | [[Category: Gupta, K]] | + | [[Category: Loll PJ]] |
| - | [[Category: Loll, P J]] | + | [[Category: Selinsky BS]] |
| - | [[Category: Selinsky, B S]] | + | [[Category: Sharkey CT]] |
| - | [[Category: Sharkey, C T]] | + | |
| - | [[Category: Dioxygenase]]
| + | |
| - | [[Category: Membrane protein]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[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.
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
Nonsteroidal antiinflammatory drugs (NSAIDs) block prostanoid biosynthesis by inhibiting prostaglandin H(2) synthase (EC 1.14.99.1). NSAIDs are either rapidly reversible competitive inhibitors or slow tight-binding inhibitors of this enzyme. These different modes of inhibition correlate with clinically important differences in isoform selectivity. Hypotheses have been advanced to explain the different inhibition kinetics, but no structural data have been available to test them. We present here crystal structures of prostaglandin H(2) synthase-1 in complex with the inhibitors ibuprofen, methyl flurbiprofen, flurbiprofen, and alclofenac at resolutions ranging from 2.6 to 2.75 A. These structures allow direct comparison of enzyme complexes with reversible competitive inhibitors (ibuprofen and methyl flurbiprofen) and slow tight-binding inhibitors (alclofenac and flurbiprofen). The four inhibitors bind to the same site and adopt similar conformations. In all four complexes, the enzyme structure is essentially unchanged, exhibiting only minimal differences in the inhibitor binding site. These results argue strongly against hypotheses that explain the difference between slow tight-binding and fast reversible competitive inhibition by invoking global conformational differences or different inhibitor binding sites. Instead, they suggest that the different apparent modes of NSAID binding may result from differences in the speed and efficiency with which inhibitors can perturb the hydrogen bonding network around Arg-120 and Tyr-355.
Structural analysis of NSAID binding by prostaglandin H2 synthase: time-dependent and time-independent inhibitors elicit identical enzyme conformations.,Selinsky BS, Gupta K, Sharkey CT, Loll PJ Biochemistry. 2001 May 1;40(17):5172-80. PMID:11318639[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Selinsky BS, Gupta K, Sharkey CT, Loll PJ. Structural analysis of NSAID binding by prostaglandin H2 synthase: time-dependent and time-independent inhibitors elicit identical enzyme conformations. Biochemistry. 2001 May 1;40(17):5172-80. PMID:11318639
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