Identification and characterization of mutations in housefly (Musca domestica) acetylcholinesterase involved in insecticide resistance
Identification and characterization of mutations in housefly (Musca domestica) acetylcholinesterase involved in insecticide resistance
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DOI：
10.1042/0264-6021:3590175
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发表时间：
2001-10-01
影响因子：
4.1
通讯作者：
Williamson, MS
中科院分区：
文献类型：
--
作者：
Walsh, SB;Dolden, TA;Williamson, MS
乙酰胆碱酯酶（AChE）对有机磷和氨基甲酸酯类杀虫剂不敏感是许多节肢动物的主要抗药性机制。然而，相关的遗传变化已被报道在乙酰胆碱酯酶基因从只有三个昆虫物种：它们的作用，赋予杀虫剂不敏感性已得到证实。使用函数表达式。只在黑腹果蝇中存在。家蝇本文报道了家蝇AChE基因的五个突变（瓦尔-180--> Leu，Gly-262 --> Ala，Gly-262-->瓦尔，Phe-327 --> Tyr和Gly-365 --> Ala），这些突变单独或组合产生了不同的抗药性谱。野生型和突变的家蝇AChE蛋白的杆状病毒表达已经证实，除了新的Gly-262 -->瓦尔突变之外，突变各自赋予相对适度水平的杀虫剂不敏感性，该突变导致对某些化合物的强得多的抗性（高达100倍）。在所有情况下，突变组合的效果都是累加的。突变引入比相应的野生型残基更大的氨基酸取代，并且位于酶的活性位点内，靠近催化三联体。根据加州电鳐和D.黑腹菌
Acetylcholinesterase (AChE) insensitive to organophosphate and carbamate insecticides has been identified as a major resistance mechanism in numerous arthropod species. However, the associated genetic changes have been reported in the AChE genes from only three insect species: their role in conferring insecticide insensitivity has been confirmed. using functional expression. only for those in Drosophila melanogaster. The housefly. Musca domestica, was one of the first insects shown to have this mechanism, here we report the occurrence of five mutations (Val-180 --> Leu, Gly-262 --> Ala, Gly-262 --> Val, Phe-327 --> Tyr and Gly-365 --> Ala) in the AChE gene of this species that, either singly or in combination, confer different spectra of insecticide resistance. The baculovirus expression of wild-type and mutated housefly AChE proteins has confirmed that the mutations each confer relatively modest levels of insecticide insensitivity except the novel Gly-262 --> Val mutation, which results in much stronger resistance (up to 100-fold) to certain compounds. In all cases the effects of mutation combinations are additive. The mutations introduce amino acid substitutions that are larger than the corresponding wild-type residues and are located within the active site of the enzyme, close to the catalytic triad. The likely influence of these substitutions on the accessibility of the different types of inhibitor and the orientation of key catalytic residues are discussed in the light of the three-dimensional structures of the AChE protein from Torpedo californica and D. melanogaster.