Molecular Characterization of the β2-like Octopamine Receptor of Helicoverpa armigera
Molecular Characterization of the β2-like Octopamine Receptor of Helicoverpa armigera
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DOI：
10.1007/s00232-021-00172-3
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发表时间：
2021-02-11
影响因子：
2.4
通讯作者：
Joshi, Manali
中科院分区：
文献类型：
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作者：
Gujar, Nidhi;Nikte, Siddhanta, V;Joshi, Manali
棉铃虫是一种毁灭性的多食性害虫和世界性害虫。有报道称这种昆虫对多种杀虫剂具有抗药性，这引起了全世界的关注。章鱼胺（OA）结合β(2)样受体（OAR）是一种GPCR，广泛分布于昆虫的神经系统中，在昆虫的生理发育中起重要作用，是杀虫剂的重要靶点。然而，目前对棉铃虫OAR （HarmOAR）的分子表征和基于该受体的化合物的合理设计尚缺乏研究。作为第一步，我们对所有的昆虫桨进行了多重序列比对，结果显示这些序列包含所有保守的a类GPCR基序。系统发育研究表明，蛋白质序列的进化枝特异性变异主要是由于ICL3环区的差异引起的。此外，以失活的人β (2)AR为模板，构建了HarmOAR的结构模型。在0.9 μ s的原子模拟中发现了HarmOAR的螺旋间接触和水分子的保守性。利用分子对接和0.3 μ s原子模拟研究了章鱼胺的结合。编译了22种对其他昆虫章鱼胺受体有活性的杀虫剂，并将其与HarmOAR对接，然后用结合自由能进行重新排序，以确定它们对棉铃虫的优先级。我们的研究表明-松油醇是一种很好的杀虫剂或驱蚊剂。
Helicoverpa armigera is a devastating polyphagous and cosmopolitan crop pest. There are reports of this insect being resistant to a variety of pesticides raising concern worldwide. The Octopamine (OA) binding beta(2)-like receptor (OAR), a GPCR, is widely distributed in the nervous system of the insect and plays essential roles in the physiology and development and thus is an important target for insecticides. Yet, the molecular characterization of the H. armigera OAR (HarmOAR) and rational design of compounds based on this receptor is lacking. As a first step, we performed multiple sequence alignment of all insect OARs, which revealed that the sequences contained all conserved class A GPCR motifs. Phylogenetic studies showed clade-specific variations in the protein sequences primarily arising owing to differences in the ICL3 loop region. Further, a structural model of HarmOAR was built using the inactive human beta(2)AR as a template. 0.9 mu s atomistic simulations revealed conserved inter helical contacts and water molecules of HarmOAR. The detailed binding of octopamine was studied using molecular docking and 0.3 mu s atomistic simulations. Twenty-two insecticides active against octopamine receptors of other insects were compiled and docked to HarmOAR followed by rescoring with binding free energies to prioritize them for H. armigera. Our study suggests alpha-terpineol to be a good candidate as an insecticide or insect repellent for Helicoverpa armigera.