Insights in 17beta-HSD1 enzyme kinetics and ligand binding by dynamic motion investigation.

ABSTRACT:

Background

Bisubstrate enzymes, such as 17beta-hydroxysteroid dehydrogenase type 1 (17beta-HSD1), exist in solution as an ensemble of conformations. 17beta-HSD1 catalyzes the last step of the biosynthesis of estradiol and, thus, it is a potentially attractive target for breast cancer treatment.

Methodology/principal findings

To elucidate the conformational transitions of its catalytic cycle, a structural analysis of all available crystal structures was performed and representative conformations were assigned to each step of the putative kinetic mechanism. To cover most of the conformational space, all-atom molecular dynamic simulations were performed using the four crystallographic structures best describing apoform, opened, occluded and closed state of 17beta-HSD1 as starti

SUBMITTER: Negri M 

PROVIDER: S-EPMC2919385 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature