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| | ==Crystal structure of human 15-ketoprostaglandin delta-13-reductase in complex with NADP and 15-keto-PGE2== | | ==Crystal structure of human 15-ketoprostaglandin delta-13-reductase in complex with NADP and 15-keto-PGE2== |
| - | <StructureSection load='2zb4' size='340' side='right' caption='[[2zb4]], [[Resolution|resolution]] 1.63Å' scene=''> | + | <StructureSection load='2zb4' size='340' side='right'caption='[[2zb4]], [[Resolution|resolution]] 1.63Å' scene=''> |
| | == Structural highlights == | | == Structural highlights == |
| - | <table><tr><td colspan='2'>[[2zb4]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZB4 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2ZB4 FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[2zb4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2ZB4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2ZB4 FirstGlance]. <br> |
| - | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=5OP:(5E,13E)-11-HYDROXY-9,15-DIOXOPROSTA-5,13-DIEN-1-OIC+ACID'>5OP</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.63Å</td></tr> |
| - | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2zb3|2zb3]], [[2zb7|2zb7]], [[2zb8|2zb8]]</td></tr>
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=5OP:(5E,13E)-11-HYDROXY-9,15-DIOXOPROSTA-5,13-DIEN-1-OIC+ACID'>5OP</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr> |
| - | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">PTGR2, ZADH1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=2zb4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zb4 OCA], [https://pdbe.org/2zb4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2zb4 RCSB], [https://www.ebi.ac.uk/pdbsum/2zb4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2zb4 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/15-oxoprostaglandin_13-oxidase 15-oxoprostaglandin 13-oxidase], with EC number [http://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'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2zb4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2zb4 OCA], [http://pdbe.org/2zb4 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2zb4 RCSB], [http://www.ebi.ac.uk/pdbsum/2zb4 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2zb4 ProSAT]</span></td></tr> | + | |
| | </table> | | </table> |
| | == Function == | | == Function == |
| - | [[http://www.uniprot.org/uniprot/PTGR2_HUMAN PTGR2_HUMAN]] 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 (By similarity).<ref>PMID:19000823</ref> | + | [https://www.uniprot.org/uniprot/PTGR2_HUMAN PTGR2_HUMAN] 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 (By similarity).<ref>PMID:19000823</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: Homo sapiens]] |
| - | [[Category: Human]] | + | [[Category: Large Structures]] |
| - | [[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: Alternative splicing]]
| + | |
| - | [[Category: Cytoplasm]]
| + | |
| - | [[Category: Nadp]]
| + | |
| - | [[Category: Oxidoreductase]]
| + | |
| - | [[Category: Rossmann fold]]
| + | |
| Structural highlights
Function
PTGR2_HUMAN 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 (By similarity).[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
- ↑ 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
- ↑ 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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