Document Type
Article
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.
Publication Date
December 2016
Publication Title
Scientific Reports
Volume
6
Issue
1
First Page
34394
Last Page
34394
DOI
10.1038/srep34394
Recommended Citation
Sawaya, Michael; Verma, Malkhey; Balendiran, Vaishnavi; Rath, Nigam; Cascio, Duilio; and Balendiran, Ganesaratnam, "Characterization of WY 14,643 and Its Complex with Aldose Reductase" (2016). Chemistry & Biochemistry Faculty Works. 8.
DOI: https://doi.org/10.1038/srep34394
Available at:
https://irl.umsl.edu/chemistry-faculty/8