jm9b00283_si_001.pdf (3.7 MB)
Colocalization Strategy Unveils an Underside Binding Site in the Transmembrane Domain of Smoothened Receptor
journal contribution
posted on 2019-10-17, 18:39 authored by Fang Zhou, Kang Ding, Yiqing Zhou, Yang Liu, Xiaoyan Liu, Fei Zhao, Yiran Wu, Xianjun Zhang, Qiwen Tan, Fei Xu, Wenfu Tan, Youli Xiao, Suwen Zhao, Houchao TaoWe unveiled an underside
binding site on smoothened receptor (SMO)
by a colocalization strategy using two structurally complementary
photoaffinity probes derived from a known ligand Allo-1. Docking study
and structural dissection identified key interactions within the site,
including hydrogen bonding, π–π interactions, and
hydrophobic interactions between Allo-1 and its contacting residues.
Taken together, our results reveal the molecular base of Allo-1 binding
and provide a basis for the design of new-generation ligands to overcome
drug resistance.