Identification of Glycine Receptor ?3 as a Colchicine-Binding Protein.

ABSTRACT: Colchicine (Col) is considered a kind of highly effective alkaloid for preventing and treating acute gout attacks (flares). However, little is known about the underlying mechanism of Col in pain treatment. We have previously developed a customized virtual target identification method, termed IFPTarget, for small-molecule target identification. In this study, by using IFPTarget and ligand similarity ensemble approach (SEA), we show that the glycine receptor alpha 3 (GlyR?3), which play a key role in the processing of inflammatory pain, is a potential target of Col. Moreover, Col binds directly to the GlyR?3 as determined by the immunoprecipitation and bio-layer interferometry assays using the synthesized Col-biotin conjugate (linked Col and biotin with polyethylene glycol). These results suggest that GlyR?3 may mediate Col-induced suppression of inflammatory pain. However, whether GlyR?3 is the functional target of Col and serves as potential therapeutic target in gouty arthritis requires further investigations.

SUBMITTER: Zhou X 

PROVIDER: S-EPMC6236057 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature