6ky6 | pdb_00006ky6

Crystal structure of a thermostable aldo-keto reductase Tm1743 in complexs with inhibitor epalrestat in space group P3221cc

spinqualitylabelsall models 6ky6, resolution 2.07Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 6ky6 is a 2 chain structure with sequence from Thema. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Ligands: CL, EPR, NAP Related: 6kiy, 6kik Gene: TM_1743, Tmari_1751 (THEMA) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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