Crystal Structure of the Commercial Herbicide, Amidosulfuron, in Complex with Arabidopsis thaliana Acetohydroxyacid Synthase

Amidosulfuron (AS) is from the commercial sulfonylurea herbicide family. It is highly effective against dicot broadleaf weeds. This herbicide targets acetohydroxyacid synthase (AHAS), the first enzyme in the branched chain amino acid biosynthesis pathway. Here, we have determined the crystal structure of AS in complex with wildtype Arabidopsis thaliana AHAS (AtAHAS) and with the resistance mutant, S653T. In both structures, the cofactor, ThDP, is modified to a peracetate adduct, consistent with time-dependent accumulative inhibition. Compared to other AHAS-inhibiting herbicides of the sulfonylurea family, AS lacks a second aromatic ring. The replacement is an aryl sulfonyl group with a reduced number of interactions with the enzyme and relatively low affinity (Ki = 4.2 mu M vs low nM when two heteroaromatic rings are present). This study shows that effective herbicides can have a relatively high Ki for plant AHAS but can still be a potent herbicide provided accumulative inhibition also occurs.

Automated summary

Amidosulfuron (AS), a commercial sulfonylurea herbicide, effectively targets dicot broadleaf weeds by inhibiting acetohydroxyacid synthase (AHAS) in the plants. The crystal structure analysis shows that AS lacks a second aromatic ring compared to other AHAS-inhibiting herbicides, but still exhibits potent herbicidal activity through accumulative inhibition. This study highlights the importance of accumulative inhibition in designing effective herbicides targeting plant AHAS.