A Structure-Activity Relationship for the Hydrolysis of Acetylamino Acids by Porcine Aminoacylase

A structure-activity relationship is presented that satisfactorily predicts the rates of hydrolysis of a series of acetylglycine derivatives by porcine aminoacylase. It is apparent that the substrate specificity of aminoacylase is mainly kinetic in origin, the observed correlation with Taftʹs Es parameter supporting the notion that enzymolysis proceeds through a mechanism that is analogous to chemical hydrolysis. It is suggested that the α-CH2CH group of those substrates that possess this moiety is conformationally immobile upon binding. This lock facilitates rapid hydrolysis and results from steric interactions between the enzyme and substrate. The incorporation of α-methyl amino acid derivatives in the structure-activity relationship is consistent with a flexible active site model and it is concluded that the α-methyl effect in this system is a binding phenomenon. It is evident that the active center of porcine aminoacylase can comfortably accommodate amino acid derivatives with side chains containing less than six carbon atoms, contrary to previous assertions. It is suggested that the binding of bulkier derivatives necessitates the distortion of the active site. Derivatives possessing β-hydroxyl groups are found to deviate from expected behavior and a nonproductive binding model is presented.