Electrostatic influence of active-site waters on the nucleophilic aromatic substitution catalyzed by 4-chlorobenzoyl-CoA dehalogenase.

Abstract:

: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.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Xu D,Guo H

doi

10.1016/j.febslet.2005.06.056

keywords:

subject

Has Abstract

pub_date

2005-08-15 00:00:00

pages

4249-53

issue

20

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(05)00801-X

journal_volume

579

pub_type

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