Comprehensive understanding of acetohydroxyacid synthase inhibition by different herbicide families
Comprehensive understanding of acetohydroxyacid synthase inhibition by different herbicide families
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DOI：
10.1073/pnas.1616142114
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发表时间：
2017-02-14
影响因子：
11.1
通讯作者：
Guddat, Luke W.
中科院分区：
文献类型：
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作者：
Garcia, Mario D.;Nouwens, Amanda;Guddat, Luke W.
五种商业除草剂家族抑制乙酰羟酸合酶（AHAS，E.C. 2.2.1.6），其是支链氨基酸生物合成途径中的第一种酶。这些除草剂的流行是由于它们的低施用率，高作物对杂草的选择性，以及对动物的低毒性。在这里，我们已经确定了拟南芥AHAS与嘧啶基苯甲酸酯（PYB）和磺酰氨基羰基三唑啉酮（SCT）除草剂家族的两个成员的复合物的晶体结构，揭示了其抑制活性的结构基础。双啼苯甲酸（Bispyribac）是PYB的一个成员，具有三个芳香环，当与A结合时，这些芳香环采用扭曲的“S”形构象。拟南芥AHAS（AtAHAS），其中嘧啶基插入除草剂结合位点最深。SCT结合使得三唑啉酮环最深地插入除草剂结合位点中。这两种化合物类填充导致活性位点的通道，从而防止底物结合。晶体结构和质谱也表明，当这些除草剂结合时，硫胺素二磷酸（ThDP）被修饰。当PYB结合时，噻唑鎓环被切割，但当SCT结合时，ThDP被修饰为硫胺素2-噻唑酮二磷酸。动力学研究表明，这些化合物不仅能引起AHAS的可逆累积抑制，而且还能引起与ThDP降解相关的抑制。在这里，我们描述的功能，有助于非常强大的除草活性所表现出的四类AHAS抑制剂。
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 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.