Identification of natural products as novel ligands for the human 5-HT2C receptor

作     者：Yao Peng Simeng Zhao Yiran Wu Haijie Cao Yueming Xu Xiaoyan Liu Wenqing Shui Jianjun Cheng Suwen Zhao Ling Shen Jun Ma Ronald J.Quinn Raymond C.Stevens Guisheng Zhong Zhi-Jie Liu 

作者机构：National Laboratory of BiomacromoleculesInstitute of BiophysicsChinese Academy of Sciences Institute of Molecular and Clinical MedicineKunming Medical University iHuman InstituteShanghai Tech University University of Chinese Academy of Sciences School of Life Science and TechnologyShanghai Tech University College of PharmacyNankai University High-throughput Molecular Drug Discovery CenterTianjin Joint Academy of Biotechnology and Medicine Eskitis Institute for Drug DiscoveryGriffith University 

出 版 物：《Biophysics Reports》 (生物物理学报(英文))

年 卷 期：2018年第4卷第1期

页      面：50-61页

核心收录：

学科分类：1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：the National Nature Science Foundation of China (31330019) the Shanghai Municipal Government Shanghai Tech University the Institute of Molecular and Clinical Medicine, Kunming Medical University 

主　　题：GPCR 5-HT 2C receptor Natural product Alkaloids 

摘      要：G protein-coupled receptors(GPCRs) constitute the largest human protein family with over 800 members,which are implicated in many important medical conditions. Serotonin receptors belong to the aminergic GPCR subfamily and play important roles in physiological and psychological activities. Structural biology studies have revealed the structures of many GPCRs in atomic details and provide the basis for the identification and investigation of the potential ligands, which interact with and modulate the ***, an integrative approach combining a focused target-specific natural compound library, a thermalshift-based screening method, affinity mass spectrometry, molecular docking, and in vitro as well as in vivo functional assay, was applied to identify(–)-crebanine and several other aporphine alkaloids as initial hits for a human serotonin receptor subtype, the 5-HT2Creceptor. Further studies illuminated key features of their binding affinity, downstream signaling and tissue reaction, providing a molecular explanation for the interaction between(–)-crebanine and human 5-HT2Creceptor.