Premium
Electrostatic influence of active‐site waters on the nucleophilic aromatic substitution catalyzed by 4‐chlorobenzoyl‐CoA dehalogenase
Author(s) -
Xu Dingguo,
Guo Hua
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.06.056
Subject(s) - dehalogenase , chemistry , active site , hydrolysis , histidine , stereochemistry , nucleophile , catalysis , residue (chemistry) , nucleophilic substitution , medicinal chemistry , enzyme , biochemistry
The 4‐chlorobenzoyl‐CoA dehalogenase catalyzes the hydrolytic dechlorination of 4‐chlorobenzoyl‐CoA via a two‐step mechanism, namely nucleophilic aromatic substitution and ester hydrolysis. The mutation of an active‐site Histidine residue has been shown to reduce the catalytic activity in both the substitution and subsequent hydrolysis steps. In this communication, we report a quantum mechanical/molecular mechanical simulation of the potential of mean force for the substitution step, which confirms the increased barrier height in the H90Q mutant and provides evidence on the electrostatic influence of two active‐site waters on the rate‐limiting barrier.