Commercial Herbicides Can Trigger the Oxidative Inactivation of Acetohydroxyacid Synthase

Acetohydroxyacid synthase (AHAS) inhibitors are highly successful commercial herbicides. New kinetic data show that the binding of these compounds leads to reversible accumulative inhibition of AHAS. Crystallographic data (to a resolution of 2.17 Ã) for an AHAS-herbicide complex shows that closure of the active site occurs when the herbicidal inhibitor binds, thus preventing exchange with solvent. This feature combined with new kinetic data shows that molecular oxygen promotes an accumulative inhibition leading to the conclusion that the exceptional potency of these herbicides is augmented by subversion of an inherent oxygenase side reaction. The reactive oxygen species produced by this reaction are trapped in the active site, triggering oxidation reactions that ultimately lead to the alteration of the redox state of the cofactor flavin adenine dinucleotide (FAD), a feature that accounts for the observed reversible accumulative inhibition. How AHAS-inhibiting herbicides work: Acetohydroxyacid synthase (AHAS) inhibitors, such as bensulfuron methyl (see picture), are successful commercial herbicides; however, their mechanism of inhibition is poorly understood. To address this issue, a new equation is proposed that both accounts for the accumulative and reversible inhibition of AHAS and explains all previous experimental data. Atom colors: C=blue; N=dark blue; O=red; S=yellow