STRUCTURE-ACTIVITY-RELATIONSHIPS IN ACETYLCHOLINESTERASE REACTIONS - HYDROLYSIS OF NONIONIC ACETIC ESTERS

The Michaelis-Menten parameters kcat, Ks(app) and the second-order rate constants kII = k2/Ks of [Naja naja oxiana venom] acetylcholinesterase-catalyzed hydrolysis of 25 acetic esters with non-ionic leaving groups were determined at 25.degree. C and pH 7.5 in 0.15 M KCl. A linear relationship between the substrate non-covalent binding capacity and the leaving group hydrophobicity, and a multiparameter correlation of the acetylation reaction rate constant logarithm with the leaving group inductive effect, hydrophobicity and steric effect, were established. The acetyl-enzyme deacetylation rate constant was calculated. Taken together, a fairly complete understanding of acetylcholinesterase specificity is possible. The data are consistent with a model of the acetylcholinesterase active site, in which the catalytically active groups are located at the bottom of a jaws-like slit with a limited range of hydrophobic walls that provide the sorption of the substrate leaving groups not longer than that in n-butyl acetate.