Molecular basis of sulfonylurea herbicide inhibition of acetohydroxyacid synthase

J Biol Chem. 2003 Feb 28;278(9):7639-44. doi: 10.1074/jbc.M211648200. Epub 2002 Dec 20.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetolactate Synthase / pharmacology*
  • Binding Sites
  • Catalytic Domain
  • Crystallography, X-Ray
  • Fungal Proteins / metabolism
  • Herbicides / pharmacology*
  • Imidazoles / pharmacology
  • Kinetics
  • Models, Chemical
  • Models, Molecular
  • Mutagenesis, Site-Directed
  • Mutation
  • Protein Binding
  • Protein Conformation
  • Protein Structure, Secondary
  • Pyrimidines / pharmacology
  • Sulfonylurea Compounds / pharmacology*


  • Fungal Proteins
  • Herbicides
  • Imidazoles
  • Pyrimidines
  • Sulfonylurea Compounds
  • chlorimuron ethyl
  • Acetolactate Synthase

Associated data

  • PDB/1N0H