Characterization of WY 14,643 and its complex with Aldose reductase
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Date
2016, 2016
Journal Title
Journal ISSN
Volume Title
Publisher
Nature Publishing Group
Abstract
The peroxisome proliferator, WY 14,643 exhibits a pure non-competitive inhibition pattern in the aldehyde reduction and in alcohol oxidation activities of human Aldose reductase (hAR). Fluorescence emission measurements of the equilibrium dissociation constants, Kd, of oxidized (hAR? NADP+) and reduced (hAR? NADPH) holoenzyme complexes display a 2-fold difference between them. Kd values for the dissociation of WY 14,643 from the oxidized (hAR? NADP+ ? WY 14,643) and reduced (hAR? NADPH? WY 14,643) ternary complexes are comparable to each other. The ternary complex structure of hAR? NADP+ ? WY 14,643 reveals the first structural evidence of a fibrate class drug binding to hAR. These observations demonstrate how fibrate molecules such as WY 14,643, besides being valued as agonists for PPAR, also inhibit hAR. ? The Author(s) 2016.
Description
Keywords
Aldehyde Reductase, Holoenzyme, Nicotinamide Adenine Dinucleotide Phosphate, Pirinixic Acid, Pyrimidine Derivative, Chemistry, Human, Protein Domain, Aldehyde Reductase, Holoenzymes, Humans, Nadp, Protein Domains, Pyrimidines
Citation
Sawaya, M. R., Verma, M., Balendiran, V., Rath, N. P., Cascio, D., & Balendiran, G. K. (2016). Characterization of WY 14,643 and its complex with Aldose reductase. Scientific Reports, 6. doi: 10.1038/srep34394