title: Commercial Herbicides Can Trigger the Oxidative Inactivation of Acetohydroxyacid Synthase.
abstract: 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 Å) 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.
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, 4072 QLD, Australia. t.lonhienne@uq.edu.au.
authors.forename: Thierry
authors.initials: T
authors.lastname: Lonhienne
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, 4072 QLD, Australia.
authors.forename: Amanda
authors.initials: A
authors.lastname: Nouwens
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, 4072 QLD, Australia.
authors.forename: Craig M
authors.identifier: http://orcid.org/0000-0002-3834-7398
authors.initials: CM
authors.lastname: Williams
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, 4072 QLD, Australia.
authors.forename: James A
authors.initials: JA
authors.lastname: Fraser
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, 4072 QLD, Australia.
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Lee
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, 4072 QLD, Australia.
authors.forename: Nicholas P
authors.initials: NP
authors.lastname: West
authors.affiliation: School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, 4072 QLD, Australia. luke.guddat@uq.edu.au.
authors.forename: Luke W
authors.identifier: http://orcid.org/0000-0002-8204-8408
authors.initials: LW
authors.lastname: Guddat
mesh_terms: D000095:Acetolactate Synthase / Q000037:antagonists & inhibitors*; D006540:Herbicides / Q000494:pharmacology*; D010084:Oxidation-Reduction
chemical_list: D006540:Herbicides; D000095:Acetolactate Synthase
keywords: accumulative inhibition; enzymes; herbicides; kinetics; structure elucidation