Skip to main content
Article
Characterization of WY 14,643 and Its Complex with Aldose Reductase
Scientific Reports (2016)
  • Michael R. Sawaya, University of California, Los Angeles
  • Malkhey Verma, The University of Manchester
  • Vaishnavi Balendiran, Youngstown State University
  • Nigam P. Rath, University of Missouri–St. Louis
  • Duilio Cascio, University of California, Los Angeles
  • Ganesaratnam K. Balendiran, Youngstown State University
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.
Disciplines
Publication Date
December 1, 2016
DOI
10.1038/srep34394
Publisher Statement
10.1038/srep34394
Citation Information
Michael R. Sawaya, Malkhey Verma, Vaishnavi Balendiran, Nigam P. Rath, et al.. "Characterization of WY 14,643 and Its Complex with Aldose Reductase" Scientific Reports Vol. 6 Iss. 1 (2016) p. 34394 - 34394
Available at: http://works.bepress.com/nigam-rath/23/
Creative Commons license
Creative Commons License
This work is licensed under a Creative Commons CC_BY International License.