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Issue 19, 2017
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Exploring the reversal of enantioselectivity on a zinc-dependent alcohol dehydrogenase

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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

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Publication details

The article was received on 26 Feb 2017, accepted on 09 Apr 2017 and first published on 18 Apr 2017


Article type: Paper
DOI: 10.1039/C7OB00482F
Citation: Org. Biomol. Chem., 2017,15, 4122-4129
  • Open access: Creative Commons BY-NC license
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    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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