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

Urmi Dhagat, Satoshi Endo, Rie Sumii, Akira Hara, Ossama El-Kabbani

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The crystal structure of human 20 alpha-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 angstrom. 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, Leu306, and Leu308 in inhibitor binding and selectivity was determined by site-directed mutagenesis.
Original languageEnglish
Pages (from-to)4844 - 4848
Number of pages5
JournalJournal of Medicinal Chemistry
Issue number15
Publication statusPublished - 2008

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