Catalysis and leaving group binding in anilide hydrolysis by chymotrypsin.
The influence of the leaving group on the reactivity of specific anilides in alpha-chymotrypsin-catalyzed hydrolysis (chymotrypsin, EC 3.4.21.2) involves both its binding to the enzyme (steric effect) and electronic nature (electronic effect). These effects are considered in terms of the stereoelectronic theory for the formation and cleavage of the tetrahedral intermediate in acyltransfer reactions. The application of this theory to the enzyme hydrolysis leads to the conclusion that the nature of the reaction products and the effectiveness of the catalysis are controlled by the orientation of the leaving group nitrogen lone pair orbital. The leaving group binding affects the formation of a reactive conformation of the enzyme tetrahedral intermediate that is presumed to intervene between the Michaelis complex and the acylenzyme. The steric and electronic effects could be separated in a straightforward fashion only in the case of equal binding of the leaving groups to the leaving-group-binding site of alpha-chymotrypsin.
D000813:Anilides; D001665:Binding Sites; D002918:Chymotrypsin / Q000378:metabolism*; D006868:Hydrolysis; D007700:Kinetics; D010649:Phenylalanine; D011487:Protein Conformation; D013379:Substrate Specificity
D000813:Anilides; D010649:Phenylalanine; D002918:Chymotrypsin