5HA7

Human Aldose Reductase in Complex with NADP+ and WY14643 in Space Group P212121

Summary for 5HA7

• Entry DOI: 10.2210/pdb5ha7/pdb
• Related: 3Q65
• Descriptor: Aldose reductase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, 2-({4-CHLORO-6-[(2,3-DIMETHYLPHENYL)AMINO]PYRIMIDIN-2-YL}SULFANYL)ACETIC ACID, ... (5 entities in total)
• Functional Keywords: alpha/beta barrel, oxidoreductase
• Biological source: Homo sapiens (Human)
• Cellular location: Cytoplasm: P15121
• Total number of polymer chains: 2
• Total formula weight: 74699.59

Authors

Sawaya, M.R.,Cascio, D.,Balendiran, G.K. (deposition date: 2015-12-30, release date: 2016-09-28, Last modification date: 2023-09-27)

Primary citation

Sawaya, M.R.,Verma, M.,Balendiran, V.,Rath, N.P.,Cascio, D.,Balendiran, G.K.
Characterization of WY 14,643 and its Complex with Aldose Reductase.
Sci Rep, 6:34394-34394, 2016

PubMed 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, K, of oxidized (hAR•NADP) and reduced (hAR•NADPH) holoenzyme complexes display a 2-fold difference between them. K 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.

PubMed: 27721416
DOI: 10.1038/srep34394

Experimental method

X-RAY DIFFRACTION (1.65 Å)