Issue 19, 2017

Exploring the reversal of enantioselectivity on a zinc-dependent alcohol dehydrogenase

Abstract

Alcohol Dehydrogenase (ADH) enzymes catalyse the reversible reduction of prochiral ketones to the corresponding alcohols. These enzymes present two differently shaped active site pockets, which dictate their substrate scope and selectivity. In this study, we computationally evaluate the effect of two commonly reported active site mutations (I86A, and W110T) on a secondary alcohol dehydrogenase from Thermoanaerobacter brockii (TbSADH) through Molecular Dynamics simulations. Our results indicate that the introduced mutations induce dramatic changes in the shape of the active site, but most importantly they impact the substrate–enzyme interactions. We demonstrate that the combination of Molecular Dynamics simulations with the tools POVME and NCIplot corresponds to a powerful strategy for rationalising and engineering the stereoselectivity of ADH variants.

Graphical abstract: Exploring the reversal of enantioselectivity on a zinc-dependent alcohol dehydrogenase

Supplementary files

Article information

Article type
Paper
Submitted
26 Febr. 2017
Accepted
09 Apr. 2017
First published
18 Apr. 2017
This article is Open Access
Creative Commons BY-NC license

Org. Biomol. Chem., 2017,15, 4122-4129

Exploring the reversal of enantioselectivity on a zinc-dependent alcohol dehydrogenase

M. A. Maria-Solano, A. Romero-Rivera and S. Osuna, Org. Biomol. Chem., 2017, 15, 4122 DOI: 10.1039/C7OB00482F

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