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| | <StructureSection load='2zb3' size='340' side='right'caption='[[2zb3]], [[Resolution|resolution]] 2.00Å' scene=''> | | <StructureSection load='2zb3' size='340' side='right'caption='[[2zb3]], [[Resolution|resolution]] 2.00Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2zb3]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Lk3_transgenic_mice Lk3 transgenic mice]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZB3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZB3 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2zb3]] 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=2ZB3 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZB3 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</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]] 2Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[2zb4|2zb4]], [[2zb7|2zb7]], [[2zb8|2zb8]]</div></td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=NDP:NADPH+DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NDP</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">Ptgr2, Zadh1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 LK3 transgenic mice])</td></tr> | + | |
| - | <tr id='activity'><td class="sblockLbl"><b>Activity:</b></td><td class="sblockDat"><span class='plainlinks'>[https://en.wikipedia.org/wiki/15-oxoprostaglandin_13-oxidase 15-oxoprostaglandin 13-oxidase], with EC number [https://www.brenda-enzymes.info/php/result_flat.php4?ecno=1.3.1.48 1.3.1.48] </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=2zb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zb3 OCA], [https://pdbe.org/2zb3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zb3 RCSB], [https://www.ebi.ac.uk/pdbsum/2zb3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zb3 ProSAT]</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=2zb3 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zb3 OCA], [https://pdbe.org/2zb3 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zb3 RCSB], [https://www.ebi.ac.uk/pdbsum/2zb3 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zb3 ProSAT]</span></td></tr> |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[https://www.uniprot.org/uniprot/PTGR2_MOUSE PTGR2_MOUSE]] Functions as 15-oxo-prostaglandin 13-reductase and acts on 15-keto-PGE1, 15-keto-PGE2, 15-keto-PGE1-alpha and 15-keto-PGE2-alpha with highest activity towards 15-keto-PGE2. Overexpression represses transcriptional activity of PPARG and inhibits adipocyte differentiation.<ref>PMID:17449869</ref>
| + | [https://www.uniprot.org/uniprot/PTGR2_MOUSE PTGR2_MOUSE] Functions as 15-oxo-prostaglandin 13-reductase and acts on 15-keto-PGE1, 15-keto-PGE2, 15-keto-PGE1-alpha and 15-keto-PGE2-alpha with highest activity towards 15-keto-PGE2. Overexpression represses transcriptional activity of PPARG and inhibits adipocyte differentiation.<ref>PMID:17449869</ref> |
| | == Evolutionary Conservation == | | == Evolutionary Conservation == |
| | [[Image:Consurf_key_small.gif|200px|right]] | | [[Image:Consurf_key_small.gif|200px|right]] |
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| | __TOC__ | | __TOC__ |
| | </StructureSection> | | </StructureSection> |
| - | [[Category: 15-oxoprostaglandin 13-oxidase]] | |
| | [[Category: Large Structures]] | | [[Category: Large Structures]] |
| - | [[Category: Lk3 transgenic mice]] | + | [[Category: Mus musculus]] |
| - | [[Category: Chuang, L M]] | + | [[Category: Chuang LM]] |
| - | [[Category: Guo, R T]] | + | [[Category: Guo RT]] |
| - | [[Category: Hu, S M]] | + | [[Category: Hu SM]] |
| - | [[Category: Ko, T P]] | + | [[Category: Ko TP]] |
| - | [[Category: Wang, A H.J]] | + | [[Category: Wang AHJ]] |
| - | [[Category: Wu, Y H]] | + | [[Category: Wu YH]] |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Rossmann fold]]
| + | |
| Structural highlights
Function
PTGR2_MOUSE Functions as 15-oxo-prostaglandin 13-reductase and acts on 15-keto-PGE1, 15-keto-PGE2, 15-keto-PGE1-alpha and 15-keto-PGE2-alpha with highest activity towards 15-keto-PGE2. Overexpression represses transcriptional activity of PPARG and inhibits adipocyte differentiation.[1]
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
PTGR2 catalyzes an NADPH-dependent reduction of the conjugated alpha,beta-unsaturated double bond of 15-keto-PGE(2), a key step in terminal inactivation of prostaglandins and suppression of PPARgamma-mediated adipocyte differentiation. Selective inhibition of PTGR2 may contribute to the improvement of insulin sensitivity with fewer side effects. PTGR2 belongs to the medium-chain dehydrogenase/reductase superfamily. The crystal structures reported here reveal features of the NADPH binding-induced conformational change in a LID motif and a polyproline type II helix which are critical for the reaction. Mutation of Tyr64 and Tyr259 significantly reduces the rate of catalysis but increases the affinity to substrate, confirming the structural observations. Besides targeting cyclooxygenase, indomethacin also inhibits PTGR2 with a binding mode similar to that of 15-keto-PGE(2). The LID motif becomes highly disordered upon the binding of indomethacin, indicating plasticity of the active site. This study has implications for the rational design of inhibitors of PTGR2.
Structural basis for catalytic and inhibitory mechanisms of human prostaglandin reductase PTGR2.,Wu YH, Ko TP, Guo RT, Hu SM, Chuang LM, Wang AH Structure. 2008 Nov 12;16(11):1714-23. PMID:19000823[2]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Chou WL, Chuang LM, Chou CC, Wang AH, Lawson JA, FitzGerald GA, Chang ZF. Identification of a novel prostaglandin reductase reveals the involvement of prostaglandin E2 catabolism in regulation of peroxisome proliferator-activated receptor gamma activation. J Biol Chem. 2007 Jun 22;282(25):18162-72. Epub 2007 Apr 21. PMID:17449869 doi:http://dx.doi.org/M702289200
- ↑ Wu YH, Ko TP, Guo RT, Hu SM, Chuang LM, Wang AH. Structural basis for catalytic and inhibitory mechanisms of human prostaglandin reductase PTGR2. Structure. 2008 Nov 12;16(11):1714-23. PMID:19000823 doi:10.1016/j.str.2008.09.007
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