Effect of electrostatic interactions in recognition of acetylcholine by acetylcholinesterase

The role of electrostatic interactions in the steering of acetylcholine to the active site of acetylcholinesterase is investigated in this study. The results obtained suggest that acetylcholinesterase's catalytic processes involve more than two steps, one of which appears to be diffusion-controlled, while the others are influenced by electrostatic interactions. The results also support the concept that the electrostatic field contributes to the guidance of the ligand upon its close proximity to the entrance of the active site gorge. On the basis of the data obtained, a prehydrolysis (pre-transition state) structure for this catalytic reaction is also proposed. The root mean square deviation of the C alpha atoms of the amino acid residues of the active site between the proposed transition state and a recently proposed transition state based on experimental data is 0.379 Angstrom. (C) 1998 Elsevier Science B.V.