Abstract
Acetohydroxyacid synthase (AHAS) (acetolactate synthase, EC ) catalyzes the first step in branched-chain amino acid biosynthesis and is the target for sulfonylurea and imidazolinone herbicides. These compounds are potent and selective inhibitors, but their binding site on AHAS has not been elucidated. Here we report the 2.8 A resolution crystal structure of yeast AHAS in complex with a sulfonylurea herbicide, chlorimuron ethyl. The inhibitor, which has a K(i) of 3.3 nm, blocks access to the active site and contacts multiple residues where mutation results in herbicide resistance. The structure provides a starting point for the rational design of further herbicidal compounds.
Highlights
Herbicides are widely used for weed control in agriculture and industry and are used by government agencies and home gardeners
The sulfonylureas and imidazolinones act by preventing branched-chain amino acid biosynthesis by virtue of their specific and potent inhibition of acetohydroxyacid synthase (AHAS)1, the first enzyme in this pathway (1, 2)
The herbicides that inhibit AHAS bear no resemblance to the substrates and are not competitive inhibitors, suggesting that they bind at a site distinct from the active site (1, 10 –13)
Summary
Herbicides are widely used for weed control in agriculture and industry and are used by government agencies and home gardeners. We report the 2.8 Å resolution crystal structure of yeast AHAS in complex with a sulfonylurea herbicide, chlorimuron ethyl. The inhibitor, which has a Ki of 3.3 nM, blocks access to the active site and contacts multiple residues where mutation results in herbicide resistance.
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