Tiwari Vikas, Sowdhamini R
National Centre for Biological Sciences, GKVK Campus, Bellary Road, Bengaluru 560 065, India.
Comput Struct Biotechnol J. 2023 Mar 6;21:2204-2214. doi: 10.1016/j.csbj.2023.03.005. eCollection 2023.
Odorant receptors (ORs) are important class of proteins involved in olfactory behaviour of insects. These are GPCR-like heptahelical transmembrane proteins with inverted topology compared to GPCR and require a co-receptor (ORco) for their function. OR function can be modulated through small molecules and negative modulation can be beneficial in case of disease vectors like . OR4 of is implicated in host recognition through human odour. is a vector for viruses that spread diseases like dengue, Zika and Chikungunya. In this study, we have attempted to model the full-length structure of OR4 and the ORco of due to lack of experimental structure. Further, we have screened a library of natural compounds (>0.3 million) along with known repellent molecules against ORco and OR4. Many natural compounds, including those from plants like (Holy Basil) and (Black pepper) were found to have better binding affinity towards ORco compared to known repellents like DEET providing an alternative to existing repellent molecules. For specific inhibitor of OR4, several natural compounds (including those from plant like Mulberry) were identified. Further, we have utilized multiple docking approaches and conservation analysis to understand the interaction between OR4 and ORco. It was observed that the residues from the seventh transmembrane helix of OR4 and pore forming helix of ORco could play an important role along with known intracellular loop 3 residues in mediating the heteromer formation of OR and ORco.
气味受体（ORs）是参与昆虫嗅觉行为的一类重要蛋白质。它们是与G蛋白偶联受体（GPCR）拓扑结构相反的七螺旋跨膜蛋白，具有类似GPCR的结构，且其功能需要一个共同受体（ORco）。OR的功能可以通过小分子进行调节，对于像[某种昆虫]这样的病媒，负调节可能是有益的。[某种昆虫]的OR4通过人类气味参与宿主识别。[某种昆虫]是传播登革热、寨卡病毒病和基孔肯雅热等疾病的病毒的病媒。在本研究中，由于缺乏实验结构，我们试图对[某种昆虫]的OR4和ORco的全长结构进行建模。此外，我们筛选了一个天然化合物库（超过30万种）以及已知的驱避分子，用于针对ORco和OR4进行测试。与避蚊胺等已知驱避剂相比，许多天然化合物，包括来自[圣罗勒]和[黑胡椒]等植物的化合物，对ORco具有更好的结合亲和力，为现有的驱避分子提供了一种替代选择。对于OR4的特异性抑制剂，我们鉴定了几种天然化合物（包括来自桑树等植物的化合物）。此外，我们利用多种对接方法和保守性分析来了解OR4和ORco之间的相互作用。据观察，OR4的第七跨膜螺旋和ORco的孔形成螺旋中的残基，连同已知的细胞内环3残基，在介导OR和ORco的异源二聚体形成中可能发挥重要作用。
