Federation Proceedings 36:794, (1977).
ACCELERATION OF ACETYLCHOLINESTERASE CATALYZED HYDROLYSIS OF NEUTRAL ACETATE ESTERS BY CERTAIN AROMATIC CATIONS. Philip Barnett* and Terrone L. Rosenberry. Depts. of Biochemistry and Neurology, Columbia University, N.Y. 10032
The catalytic site of acetylcholinesterase consists of an esteratic subsite and an anionic subsite. In certain cases, both sites can be occupied simultaneously by separate ligands. Ternary complexes involving 1) the catalytic site; 2) methyl, ethyl or n-propyl acetate; and 3) certain aromatic cations resulted in an acceleration of ester hydrolysis. Of the aromatic cations tested, only 1-methyl-2-hydroxyiminomethylpyridinium (2-PAM) and 1-methylacridinium caused acceleration; other cations were either inhibitory or gave no effect. Analysis of the steady state data indicated that acceleration arises from a decrease in the apparent Michaelis constant Kapp for the ester; the turnover number kcat is also decreased but to a smaller extent. An induced-fit model of enzyme ligand interactions can account for these observations. In this model, certain aromatic cations bind to the anionic subsite and, either prior to or concurrent with the initial ester binding at the esteratic subsite, induce a conformational change to a species with lower ester dissociation constant. (Supported by NIH Grants #NS-03304-15 and NS-11766-03, and NSF Grant #PCM73-00744.)