Molecular bases for sensitivity to acetyl-coenzyme a carboxylase inhibitors in black-grass
Molecular bases for sensitivity to acetyl-coenzyme a carboxylase inhibitors in black-grass
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DOI：
10.1104/pp.104.046144
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发表时间：
2005-03-01
期刊：
影响因子：
7.4
通讯作者：
Powles, SB
中科院分区：
文献类型：
--
作者：
Délye, C;Zhang, XQ;Powles, SB
在禾本科植物中，与来自禾本科杂草黑草（Alopecurus myosuroides [Huds.]）的叶绿体乙酰辅酶A（CoA）羧化酶（ACCase）的羧基转移酶（CT）结构域中的残基Ile-1，781和Ile-2，041同源的残基是对两类ACC酶抑制剂芳氧基苯氧基丙酸酯（APP）和环己二酮敏感性的关键决定因素。使用黑草的天然突变体，我们通过分子、生物学和生物化学方法证明，残基Trp-2，027、Asp-2，078和Gly-2，096也参与对ACC酶抑制剂的敏感性。此外，残基Trp-2027和Asp-2,078很可能参与CT活性。利用三维建模，我们发现这五个残基的侧链是相邻的，位于CT活性位点的空腔内部的表面，在APP的结合位点附近。残基1，781和2，078涉及对APP和环己二酮的敏感性，而残基21027、2，041和2，096仅涉及对API的敏感性。这表明这两类化合物的结合位点是重叠的，尽管是不同的。黑草野生型和突变CT和CT的三维模型的比较，从生物体与ACCase抑制剂的敏感性对比表明，抑制剂适合进入腔的叶绿体ACCase从草的CT活性位点，以达到其活性位点可能是紧密的。因此，该空腔的三维形状对于ACCase抑制剂的功效可能具有高度重要性。
In grasses, residues homologous to residues Ile-1,781 and Ile-2,041 in the carboxyl-transferase (CT) domain of the chloroplastic acetyl-coenzyme A (CoA) carboxylase (ACCase) from the grass weed black-grass (Alopecurus myosuroides [Huds.]) are critical determinants for sensitivity to two classes of ACCase inhibitors, aryloxyphenoxypropionates (APPs) and cyclohexanediones. Using natural mutants of black-grass, we demonstrated through a molecular, biological, and biochemical approach that residues Trp-2,027, Asp-2,078, and Gly-2,096 are also involved in sensitivity to ACCase inhibitors. In addition, residues Trp-2 027 and Asp-2,078 are very likely involved in CT activity. Using three-dimensional modeling, we found that the side chains of the five residues are adjacent, located at the surface of the inside of the cavity of the CT active site, in the vicinity of the binding site for APPs. Residues 1,781 and 2,078 are involved in sensitivity to both APPs and cyclohexanediones, whereas residues 21027, 2,041, and 2,096 are involved in sensitivity to API's only. This suggests that the binding sites for these two classes of compounds are overlapping, although distinct. Comparison of three-dimensional models for black-grass wild-type and mutant CTs and for CTs from organisms with contrasted sensitivity to ACCase inhibitors suggested that inhibitors fitting into the cavity of the CT active site of the chloroplastic ACCase from grasses to reach their active sites may be tight. The three-dimensional shape of this cavity is thus likely of high importance for the efficacy of ACCase inhibitors.