Selectivity determinants of inhibitor binding to human 20alpha-hydroxysteroid dehydrogenase: crystal structure of the enzyme in ternary complex with coenzyme and the potent inhibitor 3,5-dichlorosalicylic acid.

Abstract excerpt

The crystal structure of human 20alpha-hydroxysteroid dehydrogenase (AKR1C1) in ternary complex with the coenzyme NADP (+) and the potent inhibitor 3,5-dichlorosalicylic acid was determined at a resolution of 1.8 A. The inhibitor is held in place by a network of hydrogen bonding interactions with the active site residues Tyr55, His117, and His222. The important role of the nonconserved residues Leu54, His222,...

Topics

• 20-alpha-Hydroxysteroid Dehydrogenase
• Binding Sites
• Chlorobenzoates
• Coenzymes
• Crystallography, X-Ray
• Enzyme Inhibitors
• Humans
• Isoenzymes
• Models, Molecular
• Mutation
• Protein Binding
• Protein Structure, Secondary
• Protein Structure, Tertiary