The Journal of Membrane Biology ( IF 2.3 ) Pub Date : 2021-02-11 , DOI: 10.1007/s00232-021-00172-3 Nidhi Gujar 1 , Siddhanta V Nikte 2, 3 , Rakesh S Joshi 3, 4 , Manali Joshi 1
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Abstract
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 β2-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 β2AR as a template. 0.9 µs 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 µs 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 α-terpineol to be a good candidate as an insecticide or insect repellent for Helicoverpa armigera.
Graphic Abstract
中文翻译：
棉铃虫β 2 样章鱼胺受体的分子表征
摘要
Helicoverpa armigera是一种毁灭性的多食性和世界性作物害虫。有报道称，这种昆虫对多种杀虫剂具有抗药性，引起了全世界的关注。章鱼胺（OA）结合β2样受体（OAR）是一种GPCR，广泛分布于昆虫的神经系统中，在昆虫的生理和发育中发挥重要作用，是杀虫剂的重要靶点。然而，棉铃虫的分子特征缺乏基于这种受体的 OAR (HarmOAR) 和合理设计的化合物。作为第一步，我们对所有昆虫 OAR 进行了多序列比对，结果表明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 环区的差异而产生的。此外，HarmOAR 的结构模型是使用不活跃的人类 β 2建立的。AR 作为模板。0.9 µs 原子模拟揭示了 HarmOAR 的保守螺旋间接触和水分子。使用分子对接和 0.3 µs 原子模拟研究了章鱼胺的详细结合。编译了 22 种对其他昆虫的章鱼胺受体有活性的杀虫剂，并与 HarmOAR 对接，然后用结合自由能重新评分，以优先处理棉铃虫。我们的研究表明，α-萜品醇是棉铃虫杀虫剂或驱虫剂的良好候选者。
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