EFFECT OF ELECTROSTATIC INTERACTIONS IN RECOGNITION OF ACETYLCHOLINE BY ACETYLCHOLINESTERASE

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