Experimental validation of the predicted TGR5 binding mode model

Introduction: TGR5 (Gpbar-1) is a G-protein coupled, membrane-bound bile acid receptor, which is expressed in many human tissues. In the liver TGR5 mediated anti-inflammatory, choleretic and anti-apoptotic effects. Furthermore, the receptor has been linked to bile acid and glucose homeostasis, energy expenditure and inflammatory pathways. Thus, it is conceivable that TGR5 agonists can mediate protective effects in various liver and metabolic diseases. Aim of the present study is the development of a TGR5 structure-function model and a computational and experimental characterization of the ligand binding pocket a…