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Structural investigation of the enantioselectivity and thermostability mechanisms of esterase RhEst1 by Qi Chen; Hui-Lei Yu; Xiaolin Cheng; Jian-He Xu is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

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The esterase RhEst1 can catalyze the asymmetric hydrolysis of ethyl (±)-2,2-dimethylcyclopropane carboxylate (DmCpCe), yielding a pharmaceutically relevant (S)-carboxylic acid. A triple mutant RhEst1 showed a 5-fold increase in the catalytic activity but a significant decrease in the enantioselectivity. Further optimization studies led to a new enzyme with an additional A143T mutation, which showed both increased catalytic activity and recovered enantioselectivity as well as improved thermostability. To reveal the detailed structural mechanisms for these improved properties, we performed all-atom molecular dynamics simulations on the wild type and two mutants A147I/V148F/G254A and A143T/A147I/V148F/G254A RhEst1, in complex with R-DmCpCe and S-DmCpCe substrates, respectively. The structural stability of the enzyme variants was investigated with the residue interaction network analysis. In RhEst1, S-DmCpCe was observed to adopt a more "activated" conformation than R-DmCpCe, with the active site residues better prearranged for the reaction, leading to the improved enantioselectivity towards S-DmCpCe. The mutations in the two mutants, especially A143T, could lead to different motion pa

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Author

Qi Chen; Hui-Lei Yu; Xiaolin Cheng; Jian-He Xu

Publisher

Elsevier Science; Elsevier ; Elsevier BV (ISSN 1093-3263)

Published

2018

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Physical Sciences)