title: Structural basis for the inhibition of AKR1B10 by caffeic acid phenethyl ester (CAPE).
abstract: Caffeic acid phenethyl ester (CAPE), the major bioactive component of honeybee propolis, is a potent selective inhibitor of aldo-keto reductase family member 1B10 (AKR1B10), and a number of derivatives hold promise as potential anticancer agents. However, sequence homology between AKR1B10 and other members of the superfamily, including critical phase I metabolizing enzymes, has resulted in a concern over the selectivity of any potential therapeutic agent. To elucidate the binding mode of CAPE with AKR1B10 and to provide a tool for future in silico efforts towards identifying selective inhibitors, the crystal structure of AKR1B10 in complex with CAPE was determined. The observed interactions provide an explanation for the selectivity exhibited by CAPE for AKR1B10, and could be used to guide further derivative design.
authors.affiliation: Centre for Cellular & Structural Biology, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 East Circle, University City, Guangzhou 510006 (China).
authors.forename: Liping
authors.initials: L
authors.lastname: Zhang
authors.forename: Hong
authors.initials: H
authors.lastname: Zhang
authors.forename: Xuehua
authors.initials: X
authors.lastname: Zheng
authors.forename: Yining
authors.initials: Y
authors.lastname: Zhao
authors.forename: Shangke
authors.initials: S
authors.lastname: Chen
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Chen
authors.forename: Renwei
authors.initials: R
authors.lastname: Zhang
authors.forename: Qing
authors.initials: Q
authors.lastname: Li
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Hu
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000074408:Aldo-Keto Reductases; D002109:Caffeic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010626:Phenylethyl Alcohol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D002109:Caffeic Acids; D004791:Enzyme Inhibitors; C120471:AKR1B10 protein, human; D000074408:Aldo-Keto Reductases; D000449:Aldehyde Reductase; C055494:caffeic acid phenethyl ester; D010626:Phenylethyl Alcohol
keywords: aldose reductases; anticancer agents; binding models; caffeic acid phenethyl ester derivatives; crystal structures; selectivity