Structural insights into the mechanism of inhibition of AHAS by herbicides

Lonhienne, Thierry, Garcia, Mario D., Pierens, Gregory, Mobli, Mehdi, Nouwens, Amanda and Guddat, Luke W. (2018) Structural insights into the mechanism of inhibition of AHAS by herbicides. Proceedings of the National Academy of Sciences of the United States of America, 115 9: E1945-E1954. doi:10.1073/pnas.1714392115


Author Lonhienne, Thierry
Garcia, Mario D.
Pierens, Gregory
Mobli, Mehdi
Nouwens, Amanda
Guddat, Luke W.
Title Structural insights into the mechanism of inhibition of AHAS by herbicides
Journal name Proceedings of the National Academy of Sciences of the United States of America   Check publisher's open access policy
ISSN 1091-6490
0027-8424
Publication date 2018-01-22
Year available 2018
Sub-type Article (original research)
DOI 10.1073/pnas.1714392115
Open Access Status PMC
Volume 115
Issue 9
Start page E1945
End page E1954
Total pages 10
Place of publication Washington, DC United States
Publisher National Academy of Sciences
Language eng
Abstract Acetohydroxyacid synthase (AHAS), the first enzyme in the branched amino acid biosynthesis pathway, is present only in plants and microorganisms, and it is the target of >50 commercial herbicides. Penoxsulam (PS), which is a highly effective broad-spectrum AHAS-inhibiting herbicide, is used extensively to control weed growth in rice crops. However, the molecular basis for its inhibition of AHAS is poorly understood. This is despite the availability of structural data for all other classes of AHAS-inhibiting herbicides. Here, crystallographic data forAHAS (2.3 Å) andAHAS (2.5 Å) in complex with PS reveal the extraordinary molecular mechanisms that underpin its inhibitory activity. The structures show that inhibition of AHAS by PS triggers expulsion of two molecules of oxygen bound in the active site, releasing them as substrates for an oxygenase side reaction of the enzyme. The structures also show that PS either stabilizes the thiamin diphosphate (ThDP)-peracetate adduct, a product of this oxygenase reaction, or traps within the active site an intact molecule of peracetate in the presence of a degraded form of ThDP: thiamine aminoethenethiol diphosphate. Kinetic analysis shows that PS inhibits AHAS by a combination of events involving FAD oxidation and chemical alteration of ThDP. With the emergence of increasing levels of resistance toward front-line herbicides and the need to optimize the use of arable land, these data suggest strategies for next generation herbicide design.
Keyword FAD
ThDP
acetohydroxyacid synthase
crystal structure
herbicide
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 1087713
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
School of Chemistry and Molecular Biosciences
Centre for Advanced Imaging Publications
 
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Created: Wed, 21 Feb 2018, 11:07:04 EST