Crystal structure of plant acetohydroxyacid synthase, the target for several commercial herbicides

Garcia, Mario Daniel, Wang, Jian-Guo, Lonhienne, Thierry and Guddat, Luke William (2017) Crystal structure of plant acetohydroxyacid synthase, the target for several commercial herbicides. The FEBS Journal, 284 13: 2037-2051. doi:10.1111/febs.14102

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Author Garcia, Mario Daniel
Wang, Jian-Guo
Lonhienne, Thierry
Guddat, Luke William
Title Crystal structure of plant acetohydroxyacid synthase, the target for several commercial herbicides
Journal name The FEBS Journal   Check publisher's open access policy
ISSN 1742-4658
1742-464X
Publication date 2017-07-01
Sub-type Article (original research)
DOI 10.1111/febs.14102
Open Access Status File (Author Post-print)
Volume 284
Issue 13
Start page 2037
End page 2051
Total pages 15
Place of publication Chichester, West Sussex, United Kingdom
Publisher Wiley-Blackwell Publishing
Language eng
Abstract Acetohydroxyacid synthase (AHAS, EC 2.2.1.6) is the first enzyme in the branched-chain amino acid biosynthesis pathway. Five of the most widely used commercial herbicides (i.e. sulfonylureas, imidazolinones, triazolopyrimidines, pyrimidinyl-benzoates and sulfonylamino-cabonyl-triazolinones) target this enzyme. Here we have determined the first crystal structure of a plant AHAS in the absence of any inhibitor (2.9 Å resolution) and it shows that the herbicide-binding site adopts a folded state even in the absence of an inhibitor. This is unexpected because the equivalent regions for herbicide binding in uninhibited Saccharomyces cerevisiae AHAS crystal structures are either disordered, or adopt a different fold when the herbicide is not present. In addition, the structure provides an explanation as to why some herbicides are more potent inhibitors of Arabidopsis thaliana AHAS compared to AHASs from other species (e.g. S. cerevisiae). The elucidation of the native structure of plant AHAS provides a new platform for future rational structure-based herbicide design efforts.
Formatted abstract
Acetohydroxyacid synthase (AHAS, E.C. 2.2.1.6) is the first enzyme in the branched-chain amino acid biosynthesis pathway. Five of the most widely used commercial herbicides (i.e. sulfonylureas, imidazolinones, triazolopyrimidines, pyrimidinyl-benzoates and sulfonylamino-cabonyl-triazolinones) target this enzyme. Here we have determined the first crystal structure of a plantAHAS in the absence of any inhibitor (2.9 Å resolution) and itshows that the herbicide-binding site adopts a folded state even in the absence of an inhibitor. This is unexpected because the equivalent regions for herbicide binding in uninhibited Saccharomyces cerevisiae AHAS crystal structures are either disordered,or adopt a different fold when the herbicide is not present. In addition, the structure provides anexplanation as to why some herbicides are more potent inhibitors of Arabidopsis thaliana AHAS compared to AHASs from other species (e.g.Saccharomyces cerevisiae). The elucidation of the native structure of plant AHAS provides a new platform for future rational structure-based herbicide design efforts.
Keyword ThDP
Acetohydroxyacid synthase
Acetolactate synthase
Herbicide
Inhibitor
Q-Index Code C1
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Chemistry and Molecular Biosciences
 
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Created: Fri, 12 May 2017, 15:28:59 EST by Mrs Louise Nimwegen on behalf of School of Chemistry & Molecular Biosciences