The insecticide target in the PSST subunit of complex I

Current insecticides have been selected by sifting and winnowing hundreds o f thousands of synthetic chemicals and natural products to obtain commercia l preparations of optimal effectiveness and safety. This, process has often ended up with compounds of high potency as inhibitors of the electron tran sport chain and more specifically of complex I (NADH:ubiquinone oxidoreduct ase). Many classes of chemicals are involved and the enzyme is one of the m ost complicated known, with 43 subunits catalyzing electron transfer from N ADH to ubiquinone through flavin mononucleotide and up to eight iron-sulfur clusters. We used a potent photoaffinity ligand, (trifluoromethyl)diazirin yl-[H-3]pyridaben, to, localize the insecticide target to a single high-aff inity site in the PSST subunit that couples electron transfer from iron-sul fur cluster N2 to ubiquinone. Most importantly, all of the potent complex I -inhibiting pesticides, despite their great structural diversity, compete f or this same specific binding domain, in PSST. Finding their common mode of action and target provides insight into, shared toxicological features and potential selection for resistant pests. (C) 2001 Society of Chemical Indu stry.