Structural basis for species specific inhibition of 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1): computational study and biological validation.

ABSTRACT: 17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) catalyzes the reduction of estrone to estradiol, which is the most potent estrogen in humans. Inhibition of 17β-HSD1 and thereby reducing the intracellular estradiol concentration is thus a promising approach for the treatment of estrogen dependent diseases. In the past, several steroidal and non-steroidal inhibitors of 17β-HSD1 have been described but so far there is no cocrystal structure of the latter in complex with 17β-HSD1. However, a distinct knowledge of active site topologies and protein-ligand interactions is a prerequisite for structure-based drug design and optimization. An elegant strategy to enhance this knowledge is to compare inhibition values obtained for one compound toward ortholog proteins from various species, which ar

SUBMITTER: Klein T 

PROVIDER: S-EPMC3153478 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature