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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.

SUBMITTER: Maria-Solano MA

PROVIDER: S-EPMC5436084 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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

Maria-Solano Miguel A MA Romero-Rivera Adrian A Osuna Sílvia S

Organic & biomolecular chemistry 20170501 19

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 t ...[more]

PMID: 28436515

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