Bauer_2016_Org.Biomol.Chem_14_5639

Reference

Title : Conformational diversity and enantioconvergence in potato epoxide hydrolase 1 - Bauer_2016_Org.Biomol.Chem_14_5639
Author(s) : Bauer P , Carlsson AJ , Amrein BA , Dobritzsch D , Widersten M , Kamerlin SC
Ref : Org Biomol Chem , 14 :5639 , 2016
Abstract :

Potato epoxide hydrolase 1 (StEH1) is a biocatalytically important enzyme that exhibits rich enantio- and regioselectivity in the hydrolysis of chiral epoxide substrates. In particular, StEH1 has been demonstrated to enantioconvergently hydrolyze racemic mixes of styrene oxide (SO) to yield (R)-1-phenylethanediol. This work combines computational, crystallographic and biochemical analyses to understand both the origins of the enantioconvergent behavior of the wild-type enzyme, as well as shifts in activities and substrate binding preferences in an engineered StEH1 variant, R-C1B1, which contains four active site substitutions (W106L, L109Y, V141K and I155V). Our calculations are able to reproduce both the enantio- and regioselectivities of StEH1, and demonstrate a clear link between different substrate binding modes and the corresponding selectivity, with the preferred binding modes being shifted between the wild-type enzyme and the R-C1B1 variant. Additionally, we demonstrate that the observed changes in selectivity and the corresponding enantioconvergent behavior are due to a combination of steric and electrostatic effects that modulate both the accessibility of the different carbon atoms to the nucleophilic side chain of D105, as well as the interactions between the substrate and protein amino acid side chains and active site water molecules. Being able to computationally predict such subtle effects for different substrate enantiomers, as well as to understand their origin and how they are affected by mutations, is an important advance towards the computational design of improved biocatalysts for enantioselective synthesis.

PubMedSearch : Bauer_2016_Org.Biomol.Chem_14_5639
PubMedID: 27049844
Gene_locus related to this paper: soltu-3epoxy

Related information

Gene_locus soltu-3epoxy
Structure 4UFN

Citations formats

Bauer P, Carlsson AJ, Amrein BA, Dobritzsch D, Widersten M, Kamerlin SC (2016)
Conformational diversity and enantioconvergence in potato epoxide hydrolase 1
Org Biomol Chem 14 :5639

Bauer P, Carlsson AJ, Amrein BA, Dobritzsch D, Widersten M, Kamerlin SC (2016)
Org Biomol Chem 14 :5639