Molecular basis of sulfonylurea herbicide inhibition of acetohydroxyacid synthase

Siew Siew Pang, Luke W Guddat, Ronald G Duggleby

Research output: Contribution to journalArticleResearchpeer-review

161 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)7639 - 7644
Number of pages6
JournalJournal of Biological Chemistry
Volume278
Issue number9
DOIs
Publication statusPublished - 2003

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