Acetylcholinesterases from Drosophila melanogaster and Torpedo marmorata possess 35% identical residues. We built a homology model of the Drosophila enzyme on the basis of the known three-dimensional structure of Torpedo acetylcholinesterase, which revealed an oval rim of the active site gorge with an additional hollow which could accept small charged ligands more firmly than the corresponding surface in the Torpedo enzyme. This difference at the peripheral site, together with the kinetics of W121A and W359L mutants, suggests coordinate action of important hydrophobic residues that form the active site gorge during the catalytic process. It may also account for the activation-inhibition kinetic pattern which is characteristic for the insect enzyme.
