KINETIC AND MASS-SPECTROMETRIC ANALYSES OF THE INTERACTIONS BETWEEN PLANT ACETOHYDROXY ACID ISOMEROREDUCTASE AND THIADIAZOLE DERIVATIVES

Plant acetohydroxy acid isomeroreductase (EC 1.1.1.86), the second enz yme of the branched chain amino acid biosynthetic pathway, has been su bmitted to high-throughput screening for herbicide discovery. We repor t here the discovery of a new class of compounds belonging to the thia diazole family, which exhibit a strong inhibitory effect on this plant enzyme. Kinetic analyses revealed that these compounds act as either reversible or irreversible noncompetitive inhibitors of the plant enzy me. Reversibility or irreversibility of these compounds can be attribu ted to the nature of the additional groups of the thiadiazole ring fav oring or not favoring the formation of a covalent adduct. Mass spectro metric experiments on the complex between an irreversible compound bel onging to the thiadiazole family and the plant enzyme identified Cys49 8 as the binding site of the inhibitor.