General base catalyzed ester hydrolysis as a model of the ''charge relay'' system

Article abstract of DOI:10.1016/0045-2068(77)90003-7

The validity of the 'charge relay' system in serine esterases was examined by use of the general base catalyzed hydrolysis of ethyl chloroacetate (I) as a model system. The general base catalytic rate for 2 benzimidazoleacetic acid (II) exhibited an eightfold positive deviation from the Bronsted plot including benzimidazole, imidazole, N methylimidazole (V), and acetate ion, though in nucleophilic catalysis of the hydrolysis of p nitrophenyl acetate, the point for II conformed to the Bronsted relationship together with imidazole and benzimidazole derivatives. The positive deviation of II from the Bronsted plot for the general base catalysis was attributed to the cooperativety of the carboxyl group of II, the imidazolyl group of II, and the hydroxyl group of water. The present result provides support for the 'charge relay' system. Furthermore, the (essentially) total loss of the enzymatic activity due to N 3 methylation of histidine 57 in α chymotrypsin is discussed in comparison to the general base catalysis of V in the hydrolysis of I, which is also favorable for the 'charge relay' system.