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Colocalization Strategy Unveils an Underside Binding Site in the Transmembrane Domain of Smoothened Receptor

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 Tao

J Med Chem. 2019 Nov 14;62(21):9983-9989.

PMID: 31408335

Abstract:

We 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.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP37468329 ALLO-1 ALLO-1 37468-32-9 Price
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