Structural basis for the inhibition of AKR1B10 by caffeic acid phenethyl ester (CAPE). 2014

Liping Zhang, and Hong Zhang, and Xuehua Zheng, and Yining Zhao, and Shangke Chen, and Yunyun Chen, and Renwei Zhang, and Qing Li, and Xiaopeng Hu
Centre for Cellular & Structural Biology, School of Pharmaceutical Sciences, Sun Yat-sen University, 132 East Circle, University City, Guangzhou 510006 (China).

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.

UI MeSH Term Description Entries
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D010626 Phenylethyl Alcohol An antimicrobial, antiseptic, and disinfectant that is used also as an aromatic essence and preservative in pharmaceutics and perfumery. Benzyl Carbinol,Phenethyl Alcohol,Phenylethanol,2-Phenylethanol,beta-Phenylethanol,2 Phenylethanol,Alcohol, Phenethyl,Alcohol, Phenylethyl,Carbinol, Benzyl,beta Phenylethanol
D002109 Caffeic Acids A class of phenolic acids related to chlorogenic acid, p-coumaric acid, vanillic acid, etc., which are found in plant tissues. It is involved in plant growth regulation. Acids, Caffeic
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004791 Enzyme Inhibitors Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction. Enzyme Inhibitor,Inhibitor, Enzyme,Inhibitors, Enzyme
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000074408 Aldo-Keto Reductases A family of NADPH-dependent oxidoreductases that reduce carbonyl substrates including sugar-aldehydes, KETOSTEROIDS; keto-prostaglandins, and QUINONES. They are monomers of approximately 37 KDa and are characterized by a parallel beta-8 (BETA SHEET)-alpha 8 (ALPHA HELICES)-barrel structure that contains the NADP binding site. This conformation favors aromatic and apolar substrates. Aldo-Keto Reductase,Aldo-Keto Reductase Family,Aldo-Keto Reductase Superfamily,Aldo Keto Reductase,Aldo Keto Reductase Family,Aldo Keto Reductase Superfamily,Aldo Keto Reductases,Reductase, Aldo-Keto,Reductases, Aldo-Keto
D000449 Aldehyde Reductase An enzyme that catalyzes reversibly the oxidation of an aldose to an alditol. It possesses broad specificity for many aldoses. EC 1.1.1.21. Aldose Reductase,Aldose Reductase Ia,Aldose Reductase Ib,Erythrose Reductase,Xylose Reductase,Reductase Ia, Aldose,Reductase Ib, Aldose,Reductase, Aldehyde,Reductase, Aldose,Reductase, Erythrose,Reductase, Xylose
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D015394 Molecular Structure The location of the atoms, groups or ions relative to one another in a molecule, as well as the number, type and location of covalent bonds. Structure, Molecular,Molecular Structures,Structures, Molecular

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