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 acetylcholinesterase govern the acceptance of the acetyl/butyryl moiety of the choline esters. As an insecticide-resistance mutation has been evidenced in the acyl pocket of Drosophila melanogaster and Musca domestica acetylcholinesterase we investigated the possibility of linking changes in acetyl/butyrylthiocholine specificity with mutations in insect acetylcholinesterase. We thus analyzed the effect of 28 mutations in Drosophila enzyme on acetyl/butyrylthiocholine, N-methyl/N-propyl-carbamates and ethyl/methyl-paraoxon preference. It appeared that the highest changes on acetyl/butyrylthiocholine and N-propyl/N-methyl-carbamates preference were due to mutations in the acyl pocket. Nevertheless, other insecticide-resistance mutations, not located in the acyl pocket, also modified these substrate preferences. Moreover, the effect of mutations in the acyl pocket was hidden when some other insecticide-resistance mutations were combined in the enzyme. Consequently, acetyl/butyrylthiocholine preference alteration cannot be used as a marker to localize a mutation in the insect AChE. (Résumé d'auteur