Homology built model of acetylcholinesterase from Drosophila melanogaster

Acetylcholinesterases from Drosophila melanogaster and Torpedo marmorata po ssess 35% identical residues. We built a homology model of the Drosophila e nzyme on the basis of the known three-dimensional structure of Torpedo acet ylcholinesterase, which revealed an oval rim of the active site gorge with an additional hollow which could accept small charged ligands more firmly t han the corresponding surface in the Topedo enzyme, This difference at the peripheral site, together with the kinetics of W121A and W359L mutants, sug gests coordinate action of important hydrophobic residues that form the act ive site gorge during the catalytic process. It may also account for the ac tivation-inhibition kinetic pattern which is characteristic for the insect enzyme.