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.
|Pages (from-to)||4844 - 4848|
|Number of pages||5|
|Journal||Journal of Medicinal Chemistry|
|Publication status||Published - 2008|
Dhagat, U., Endo, S., Sumii, R., Hara, A., & El-Kabbani, O. (2008). 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. Journal of Medicinal Chemistry, 51(15), 4844 - 4848.