title: 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.
authors.affiliation: Department of Chemistry, University of New Mexico, Albuquerque, NM 87131, USA.
authors.forename: Dingguo
authors.initials: D
authors.lastname: Xu
authors.forename: Hua
authors.initials: H
authors.lastname: Guo
mesh_terms: D019943:Amino Acid Substitution; D024322:Amino Acids, Aromatic / Q000737:chemistry / Q000235:genetics; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics; D001665:Binding Sites / Q000235:genetics; D002384:Catalysis; D003198:Computer Simulation; D006639:Histidine / Q000737:chemistry* / Q000235:genetics; D006867:Hydrolases / Q000737:chemistry* / Q000235:genetics; D009154:Mutation; D055672:Static Electricity; D014867:Water / Q000737:chemistry
chemical_list: D024322:Amino Acids, Aromatic; D001426:Bacterial Proteins; D014867:Water; D006639:Histidine; D006867:Hydrolases; C084333:4-chlorobenzoyl coenzyme A dehalogenase