Identification of Natural Products As Novel Ligands for the Human 5-HT Receptor

Overview

Journal Biophys Rep

Specialty Biochemistry

Date 2018 Mar 27

PMID 29577069

Citations 8

Authors

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

Affiliations

Soon will be listed here.

Abstract

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 receptors. Here, an integrative approach combining a focused target-specific natural compound library, a thermal-shift-based screening method, affinity mass spectrometry, molecular docking, and as well as functional assay, was applied to identify (-)-crebanine and several other aporphine alkaloids as initial hits for a human serotonin receptor subtype, the 5-HT receptor. 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-HT receptor.

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