Evaluation of the inhibitory effect of abamectin on mammalian butyrylcholinesterase: Enzyme kinetic and molecular docking studies

Abamectin, a blend of the natural avermectins B-1a and B-1b, is a widely-used insecticide/miticide with relatively low toxicity to mammals. Exposure to high doses of it, however, leads to cholinergic-like neurotoxic effects. Butyrylcholinesterase, which is best known for its abundant presence in plasma, is a serine hydrolase loosely coupled with the cholinergic system. It protects and supports the neurotransmitter function of its sister enzyme acetylcholinesterase. Here, using experimental and computational studies, we provide evidence demonstrating that abamectin is a potent (IC50 = 10.6 mu M; K-i = 2.26 +/- 0.35 mu M) inhibitor of horse serum butyrylcholinesterase and that it interacts with the enzyme in a reversible, competitive manner predictively to block the mouth of the active-site gorge of the enzyme and to bind to several critical residues that normally bind/hydrolyze choline esters.