5K3S

Crystal structure of Arabidopsis thaliana acetohydroxyacid synthase in complex with a pyrimidinyl-benzoate herbicide, bispyribac-sodium

5K3S の概要

• エントリーDOI: 10.2210/pdb5k3s/pdb
• 関連するPDBエントリー: 5K2O
• 分子名称: Acetolactate synthase, chloroplastic, MAGNESIUM ION, FLAVIN-ADENINE DINUCLEOTIDE, ... (6 entities in total)
• 機能のキーワード: ahas, acetohydroxyacid synthase, acetolactate synthase, herbicide, bispyribac-sodium, thiamin diphosphate, fad, pyrimidinyl-benzoate, transferase
• 由来する生物種: Arabidopsis thaliana (Mouse-ear cress)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 66244.18

構造登録者

Garcia, M.D.,Lonhienne, T.,Guddat, L.W. (登録日: 2016-05-19, 公開日: 2017-02-08, 最終更新日: 2024-10-30)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.873 Å)