3BCJ

Crystal structure of Aldose Reductase complexed with 2S4R (Stereoisomer of Fidarestat, 2S4S) at 0.78 A

Summary for 3BCJ

• Entry DOI: 10.2210/pdb3bcj/pdb
• Related: 1PWM 1X98
• Descriptor: Aldose reductase, NADP NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE, CITRIC ACID, ... (5 entities in total)
• Functional Keywords: aldo-keto reductases, diabetes, drug design, polyl pathway, acetylation, cataract, cytoplasm, nadp, oxidoreductase, polymorphism
• Biological source: Homo sapiens (human)
• Cellular location: Cytoplasm: P15121
• Total number of polymer chains: 1
• Total formula weight: 37113.09

Authors

Zhao, H.T.,El-Kabbani, O. (deposition date: 2007-11-13, release date: 2008-04-08, Last modification date: 2023-11-01)

Primary citation

Zhao, H.T.,Hazemann, I.,Mitschler, A.,Carbone, V.,Joachimiak, A.,Ginell, S.,Podjarny, A.,El-Kabbani, O.
Unusual Binding Mode of the 2S4R Stereoisomer of the Potent Aldose Reductase Cyclic Imide Inhibitor Fidarestat (2S4S) in the 15 K Crystal Structure of the Ternary Complex Refined at 0.78 A Resolution: Implications for the Inhibition Mechanism
J.Med.Chem., 51:1478-1481, 2008

PubMed Abstract: The structure of human aldose reductase in complex with the 2 S4 R stereoisomer of the potent inhibitor Fidarestat ((2 S,4 S)-6-fluoro-2',5'-dioxospiro-[chroman-4,4'-imidazoline]-2-carboxamide) was determined at 15 K and a resolution of 0.78 A. The structure of the complex provides experimental evidence for the inhibition mechanism in which Fidarestat is initially bound neutral and then becomes negatively charged by donating the proton at the 1'-position nitrogen of the cyclic imide ring to the N2 atom of the catalytic His110.

PubMed: 18284183
DOI: 10.1021/jm701514k

Experimental method

X-RAY DIFFRACTION (0.78 Å)