Format

Send to

Choose Destination
J Med Chem. 2008 Aug 14;51(15):4844-8. doi: 10.1021/jm8003575. Epub 2008 Jul 12.

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.

Author information

1
Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Parkville, Victoria, Australia.

Abstract

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, Leu306, and Leu308 in inhibitor binding and selectivity was determined by site-directed mutagenesis.

PMID:
18620380
DOI:
10.1021/jm8003575
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for American Chemical Society
Loading ...
Support Center