6kiy
From Proteopedia
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| - | '''Unreleased structure''' | ||
| - | + | ==Crystal structure of a thermostable aldo-keto reductase Tm1743 in complex with inhibitor Epalrestat== | |
| + | <StructureSection load='6kiy' size='340' side='right'caption='[[6kiy]], [[Resolution|resolution]] 1.90Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6kiy]] is a 1 chain structure with sequence from [http://en.wikipedia.org/wiki/Thema Thema]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6KIY OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=6KIY FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=EPR:{5-[(2E)-2-METHYL-3-PHENYLPROP-2-EN-1-YLIDENE]-4-OXO-2-THIOXO-1,3-THIAZOLIDIN-3-YL}ACETIC+ACID'>EPR</scene>, <scene name='pdbligand=NAP:NADP+NICOTINAMIDE-ADENINE-DINUCLEOTIDE+PHOSPHATE'>NAP</scene></td></tr> | ||
| + | <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[6kik|6kik]]</td></tr> | ||
| + | <tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">TM_1743 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=243274 THEMA])</td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=6kiy FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6kiy OCA], [http://pdbe.org/6kiy PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6kiy RCSB], [http://www.ebi.ac.uk/pdbsum/6kiy PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6kiy ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Tolrestat and epalrestat have been characterized as noncompetitive inhibitors of aldo-ketone reductase 1B1 (AKR1B1), a leading drug target for the treatment of type 2 diabetes complications. However, clinical applications are limited for most AKR1B1 inhibitors due to adverse effects of cross-inhibition with other AKRs. Here, we report an atypical competitive binding and inhibitory effect of tolrestat on the thermostable AKR Tm1743 from Thermotoga maritima. Analysis of the Tm1743 crystal structure in complex with tolrestat alone and epalrestat-NADP(+) shows that tolrestat, but not epalrestat, binding triggers dramatic conformational changes in the anionic site and cofactor binding pocket that prevents accommodation of NADP(+) . Enzymatic and molecular dynamics simulation analyses further confirm tolrestat as a competitive inhibitor of Tm1743. | ||
| - | + | Tolrestat acts atypically as a competitive inhibitor of the thermostable aldo-keto reductase Tm1743 from Thermotoga maritima.,Zhang C, Min Z, Liu X, Wang C, Wang Z, Shen J, Tang W, Zhang X, Liu D, Xu X FEBS Lett. 2020 Feb;594(3):564-580. doi: 10.1002/1873-3468.13630. Epub 2019 Oct, 17. PMID:31573681<ref>PMID:31573681</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| - | [[Category: | + | <div class="pdbe-citations 6kiy" style="background-color:#fffaf0;"></div> |
| - | [[Category: | + | == References == |
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Thema]] | ||
| + | [[Category: Liu, X M]] | ||
| + | [[Category: Min, Z Z]] | ||
[[Category: Wang, C]] | [[Category: Wang, C]] | ||
| - | [[Category: | + | [[Category: Xu, X L]] |
| - | [[Category: Zhang, C | + | [[Category: Zhang, C Y]] |
| + | [[Category: Aldo-ketone reductase]] | ||
| + | [[Category: Competitive inhibitor]] | ||
| + | [[Category: Epalrestat]] | ||
| + | [[Category: Nadph]] | ||
| + | [[Category: Oxidoreductase]] | ||
Revision as of 07:16, 8 April 2020
Crystal structure of a thermostable aldo-keto reductase Tm1743 in complex with inhibitor Epalrestat
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