Crystal structure of yeast acetohydroxyacid synthase: a target for herbicidal inhibitors

J Mol Biol. 2002 Mar 22;317(2):249-62. doi: 10.1006/jmbi.2001.5419.

Abstract

Acetohydroxyacid synthase (AHAS; EC 4.1.3.18) catalyzes the first step in branched-chain amino acid biosynthesis. The enzyme requires thiamin diphosphate and FAD for activity, but the latter is unexpected, because the reaction involves no oxidation or reduction. Due to its presence in plants, AHAS is a target for sulfonylurea and imidazolinone herbicides. Here, the crystal structure to 2.6 A resolution of the catalytic subunit of yeast AHAS is reported. The active site is located at the dimer interface and is near the proposed herbicide-binding site. The conformation of FAD and its position in the active site are defined. The structure of AHAS provides a starting point for the rational design of new herbicides.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acetolactate Synthase / chemistry*
  • Acetolactate Synthase / genetics
  • Acetolactate Synthase / metabolism*
  • Amino Acid Sequence
  • Binding Sites
  • Catalytic Domain
  • Crystallography, X-Ray
  • Dimerization
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism
  • Flavin-Adenine Dinucleotide / chemistry
  • Flavin-Adenine Dinucleotide / metabolism
  • Herbicides / chemistry
  • Herbicides / metabolism*
  • Imidazoles / chemistry
  • Imidazoles / metabolism*
  • Magnesium / chemistry
  • Magnesium / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Niacin / analogs & derivatives*
  • Niacin / chemistry
  • Niacin / metabolism*
  • Protein Conformation
  • Sequence Homology, Amino Acid
  • Thiamine Pyrophosphate / chemistry
  • Thiamine Pyrophosphate / metabolism
  • Yeasts / enzymology*

Substances

  • Enzyme Inhibitors
  • Herbicides
  • Imidazoles
  • Flavin-Adenine Dinucleotide
  • Niacin
  • imazapyr
  • Acetolactate Synthase
  • Magnesium
  • Thiamine Pyrophosphate

Associated data

  • PDB/1JSC