Ferrogasse, Vienna, Austria.
School of Life, Health and Chemical Sciences, Open University, Milton Keynes, United Kingdom.
PLoS One. 2018 Apr 3;13(4):e0194724. doi: 10.1371/journal.pone.0194724. eCollection 2018.
It is generally recognized that insect odorant binding proteins (OBPs) mediate the solubilisation and transport of hydrophobic odorant molecules and contribute to the sensitivity of the insect olfactory system. However, the exact mechanism by which OBPs deliver odorants to olfactory receptors and their role, if any, as selectivity filters for specific odorants, are still a matter of debate. In the case of Anopheles gambiae, recent studies indicate that ligand discrimination is effected through the formation of heterodimers such as AgamOBP1 and AgamOBP4 (odorant binding proteins 1 and 4 from Anopheles gambiae). Furthermore, AgamOBPs have been reported to be promiscuous in binding more than one ligand simultaneously and repellents such as DEET (N,N-diethyl-3-toluamide) and 6-MH (6-methyl-5-hepten-2-one) interact directly with mosquito OBPs and/or compete for the binding of attractive odorants thus disrupting OBP heterodimerisation. In this paper, we propose mechanisms of action of DEET and 6-MH. We also predict that ligand binding can occur in several locations of AgamOBP1 with partial occupancies and propose structural features appropriate for repellent pharmacophores.
人们普遍认为昆虫气味结合蛋白（OBP）介导疏水性气味分子的溶解和运输，并有助于昆虫嗅觉系统的敏感性。然而，OBP 将气味传递给嗅觉受体的确切机制，以及它们作为特定气味选择性过滤器的作用（如果有的话），仍然存在争议。在冈比亚按蚊的情况下，最近的研究表明，配体的区分是通过形成异二聚体来实现的，例如 AgamOBP1 和 AgamOBP4（冈比亚按蚊的气味结合蛋白 1 和 4）。此外，据报道，AgamOBPs 具有同时结合一种以上配体的混杂性，避蚊胺（N，N-二乙基-3-甲苯酰胺）和 6-MH（6-甲基-5-庚烯-2-酮）等驱虫剂直接与蚊子 OBPs 相互作用，或争夺有吸引力的气味的结合，从而破坏 OBP 异二聚化。在本文中，我们提出了避蚊胺和 6-MH 的作用机制。我们还预测，配体结合可以在 AgamOBP1 的几个位置发生，具有部分占有率，并提出适合驱虫剂药效团的结构特征。
