Acetylcholinesterase as Polyelectrolyte: Inhibition by Alkylammonium Ions

It is shown that the influence of alkylammonium salts on the acetylcholinesterase-catalyzed hydrolysis of cationic substrates is caused by two factors: (A) nonspecific binding (condensation) of inhibitory cations on the polyanionic enzyme molecule due to electrostatic interactions, and (B) binding of the inhibitor in the active site of the enzyme due to hydrophobic interaction, accompanied by the release of a fraction of condensed counterions during the binding process. The description of the electrostatic effect upon ligand binding as a polyionic field effect is in complete agreement with the recent structural data which have indicated the absence of the functionally important "anionic point" in the choline-binding pocket of acetylcholinesterase.