Structural highlights
Function
[ALDR_HUMAN] Catalyzes the NADPH-dependent reduction of a wide variety of carbonyl-containing compounds to their corresponding alcohols with a broad range of catalytic efficiencies.
Publication Abstract from PubMed
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.
Characterization of WY 14,643 and its Complex with Aldose Reductase.,Sawaya MR, Verma M, Balendiran V, Rath NP, Cascio D, Balendiran GK Sci Rep. 2016 Oct 10;6:34394. doi: 10.1038/srep34394. PMID:27721416[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Sawaya MR, Verma M, Balendiran V, Rath NP, Cascio D, Balendiran GK. Characterization of WY 14,643 and its Complex with Aldose Reductase. Sci Rep. 2016 Oct 10;6:34394. doi: 10.1038/srep34394. PMID:27721416 doi:http://dx.doi.org/10.1038/srep34394
