Is acetyl/butyrylcholine specificity a marker for insecticide-resistance mutations in insect acetylcholinesterase?

Substrate specificity has been widely studied in vertebrate cholinesterases and it has been shown that two phenylalanines in the acyl pocket of acetyl cholinesterase govern the acceptance of the acetyl/butyryl moiety of the ch oline esters. As an insecticide-resistance mutation has been evidenced in t he acyl pocket of Drosophila melanogaster and Musca domestica acetylcholine sterase we investigated the possibility of linking changes in acetyl/butyry lthiocholine specificity with mutations in insect acetylcholinesterase. We thus analyzed the effect of 28 mutations in Drosophila enzyme on acetyl/but yrylthiocholine, N-methyl/N-propyl-carbamates and ethyl/methyl-paraoxon pre ference. It appeared that the highest changes on acetyl/butyrylthiocholine and N-propyl/N-methyl-carbamates preference were due to mutations in the ac yl pocket. Nevertheless, other insecticide-resistance mutations, not locate d in the acyl pocket, also modified these: substrate preferences. Moreover, the effect of mutations in the acyl pocket was hidden when some other inse cticide-resistance mutations were combined in the enzyme. Consequently, ace tyl/butyrylthiocholine preference alteration cannot be used as a marker to localize a mutation in the insect AChE. (C) 2000 Society of Chemical Indust ry.