5K6T

Crystal structure of Arabidopsis thaliana acetohydroxyacid synthase in complex with a sulfonylamino-carbonyl-triazolinone herbicide, propoxycarbazone-sodium

Summary for 5K6T

• Entry DOI: 10.2210/pdb5k6t/pdb
• Related: 5K2O 5K3S 5K6Q 5K6R
• Descriptor: Acetolactate synthase, chloroplastic, MAGNESIUM ION, FLAVIN-ADENINE DINUCLEOTIDE, ... (8 entities in total)
• Functional Keywords: ahas, acetohydroxyacid synthase, acetolactate synthase, herbicide, propoxycarbazone sodium, thiamin diphosphate, fad, sulfonylamino-carbonyl-triazolinone, transferase
• Biological source: Arabidopsis thaliana (Mouse-ear cress)
• Total number of polymer chains: 1
• Total formula weight: 66486.60

Authors

Garcia, M.D.,Lonhienne, T.,Guddat, L.W. (deposition date: 2016-05-25, release date: 2017-02-08, Last modification date: 2024-10-30)

Primary citation

Garcia, M.D.,Nouwens, A.,Lonhienne, T.G.,Guddat, L.W.
Comprehensive understanding of acetohydroxyacid synthase inhibition by different herbicide families.
Proc. Natl. Acad. Sci. U.S.A., 114:E1091-E1100, 2017

PubMed Abstract: Five 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 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 AHAS (AHAS) 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.

PubMed: 28137884
DOI: 10.1073/pnas.1616142114

Experimental method

X-RAY DIFFRACTION (2.763 Å)