The carboxyltransferase activity of the apicoplast acetyl-CoA carboxylase of Toxoplasma gondii is the target of aryloxyphenoxypropionate inhibitors
The carboxyltransferase activity of the apicoplast acetyl-CoA carboxylase of Toxoplasma gondii is the target of aryloxyphenoxypropionate inhibitors
复制标题
DOI：
10.1074/jbc.m200455200
复制
发表时间：
2002-06-28
影响因子：
4.8
通讯作者：
Gornicki, P
中科院分区：
文献类型：
--
作者：
Jelenska, J;Sirikhachornkit, A;Gornicki, P
芳氧基苯氧基丙酸酯除草剂对顶复门寄生虫弓形虫生长的抑制与这些化合物对其乙酰辅酶A羧化酶（ACC）的抑制有关。在此，弓形虫顶端体 ACC 的全长片段和 C 端片段以及胞质 ACC 的 C 端片段在大肠杆菌中表达。可溶的重组蛋白显示出预期的酶活性。依赖于表达的弓形虫 ACC 上生长的酵母基因替换菌株是通过酵母 ACC1 无效突变的互补而衍生的。诺氧基苯氧基丙酸酯的体外和体内测试表明，弓形虫 ACC 的羧基转移酶结构域是此类抑制剂的靶点。胞浆弓形虫 ACC 对芳氧基苯氧基丙酸盐具有抗性。两种弓形虫同工酶都对环己烷二酮具有抗性，环己烷二酮是另一类针对草质体 ACC 的抑制剂。
Inhibition of growth of the apicomplexan parasite Toxoplasma gondii by aryloxyphenoxypropionate herbicides has been correlated with the inhibition of its acetyl-CoA carboxylase (ACC) by these compounds. Here, full-length and C-terminal fragments of T. gondii apicoplast ACC as well as C-terminal fragments of the cytosolic ACC were expressed in Escherichia coli. The recombinant proteins that were soluble showed the expected enzymatic activities. Yeast gene-replacement strains depending for growth on the expressed T. gondii ACC were derived by complementation of a yeast ACC1 null mutation. In vitro and in vivo tests with noxyphenoxypropionates showed that the carboxyltransferase domain of the apicoplast T. gondii ACC is the target for this class of inhibitors. The cytosolic T. gondii ACC is resistant to aryloxyphenoxypropionates. Both T. gondii isozymes are resistant to cyclohexanediones, another class of inhibitors targeting the ACC of grass plastids.