5k3s
Crystal structure of Arabidopsis thaliana acetohydroxyacid synthase in complex with a pyrimidinyl-benzoate herbicide, bispyribac-sodium
Structural highlights
FunctionILVB_ARATH Catalyzes the formation of acetolactate from pyruvate, the first step in valine and isoleucine biosynthesis.[1] [2] [:][3] [4] [5] [6] [7] [8] Publication Abstract from PubMedFive commercial herbicide families inhibit acetohydroxyacid synthase (AHAS, E.C. 2.2.1.6), which is the first enzyme in the branched-chain amino acid biosynthesis pathway. The popularity of these herbicides is due to their low application rates, high crop vs. weed selectivity, and low toxicity in animals. Here, we have determined the crystal structures of Arabidopsis thaliana AHAS in complex with two members of the pyrimidinyl-benzoate (PYB) and two members of the sulfonylamino-carbonyl-triazolinone (SCT) herbicide families, revealing the structural basis for their inhibitory activity. Bispyribac, a member of the PYBs, possesses three aromatic rings and these adopt a twisted "S"-shaped conformation when bound to A. thaliana AHAS (AtAHAS) with the pyrimidinyl group inserted deepest into the herbicide binding site. The SCTs bind such that the triazolinone ring is inserted deepest into the herbicide binding site. Both compound classes fill the channel that leads to the active site, thus preventing substrate binding. The crystal structures and mass spectrometry also show that when these herbicides bind, thiamine diphosphate (ThDP) is modified. When the PYBs bind, the thiazolium ring is cleaved, but when the SCTs bind, ThDP is modified to thiamine 2-thiazolone diphosphate. Kinetic studies show that these compounds not only trigger reversible accumulative inhibition of AHAS, but also can induce inhibition linked with ThDP degradation. Here, we describe the features that contribute to the extraordinarily powerful herbicidal activity exhibited by four classes of AHAS inhibitors. Comprehensive understanding of acetohydroxyacid synthase inhibition by different herbicide families.,Garcia MD, Nouwens A, Lonhienne TG, Guddat LW Proc Natl Acad Sci U S A. 2017 Feb 14;114(7):E1091-E1100. doi:, 10.1073/pnas.1616142114. Epub 2017 Jan 30. PMID:28137884[9] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
| ||||||||||||||||||||
