Herbicide-binding sites revealed in the structure of plant acetohydroxyacid synthase
Herbicide-binding sites revealed in the structure of plant acetohydroxyacid synthase
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DOI：
10.1073/pnas.0508701103
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发表时间：
2006-01-17
影响因子：
11.1
通讯作者：
Duggleby, RG
中科院分区：
文献类型：
--
作者：
McCourt, JA;Pang, SS;Duggleby, RG
磺酰脲类和咪唑啉酮类是有效的商业除草剂家族。它们是全世界农民最受欢迎的选择之一，因为它们对动物无毒，并且具有高度选择性。这些除草剂通过靶向乙酰羟酸合成酶来抑制植物中的支链氨基酸生物合成（AHAS，EC www.example.com）。本报告描述了拟南芥AHAS与五种磺酰脲（分辨率为2.5埃）和咪唑啉酮，咪唑喹（IQ; 2.8埃）复合的3D结构。这两类分子都不具有模拟酶底物的结构，但都通过阻断通道来抑制，通过该通道获得活性位点。磺酰脲类药物接近催化中心的5埃范围内，催化中心是辅因子二磷酸硫胺素的C2原子，而IQ距离该原子至少7埃。结合磺酰脲类的10个氨基酸残基也结合IQ。另外六个残基只与磺酰脲类相互作用，而有两个残基结合IQ，但不结合磺酰脲类。因此，这两类抑制剂占据部分重叠的位点，但采用不同的结合模式。由于干扰AHAS抑制作用的突变的出现，抗性杂草的出现越来越多，现在是一个世界性的问题。这里描述的结构为理解这些突变提供了合理的分子基础，从而允许开发更复杂的AHAS抑制剂。对于与商业除草剂复合的任何植物蛋白，先前没有描述过结构。
The sulfonylureas and imidazolinones are potent commercial herbicide families. They are among the most popular choices for farmers worldwide, because they are nontoxic to animals and highly selective. These herbicides inhibit branched-chain amino acid biosynthesis in plants by targeting acetohydroxyacid synthase (AHAS, EC 2.2.1.6). This report describes the 3D structure of Arabidopsis thaliana AHAS in complex with five sulfonylureas (to 2.5 angstrom resolution) and with the imidazolinone, imazaquin (IQ; 2.8 angstrom). Neither class of molecule has a structure that mimics the substrates for the enzyme, but both inhibit by blocking a channel through which access to the active site is gained. The sulfonylureas approach within 5 angstrom of the catalytic center, which is the C2 atom of the cofactor thiamin diphosphate, whereas IQ is at least 7 angstrom from this atom. Ten of the amino acid residues that bind the sulfonylureas also bind IQ. Six additional residues interact only with the sulfonylureas, whereas there are two residues that bind IQ but not the sulfonylureas. Thus, the two classes of inhibitor occupy partially overlapping sites but adopt different modes of binding. The increasing emergence of resistant weeds due to the appearance of mutations that interfere with the inhibition of AHAS is now a worldwide problem. The structures described here provide a rational molecular basis for understanding these mutations, thus allowing more sophisticated AHAS inhibitors to be developed. There is no previously described structure for any plant protein in complex with a commercial herbicide.