Binding mode of 6ECDCA, a potent bile acid agonist of the farnesoid X receptor (FXR)

Based on the folding conservation across the nuclear receptor superfamily and the sequence homology with RAR-γ, we report the construction of a three dimensional model of the ligand binding domain of FXR. The model is exploited for the elucidation of the binding mode of 6α-ethyl-chenodeoxycholic acid. The results of the docking experiments give quite clear indications that the bile acid derivative would bind the receptor in a mode significantly different than that observed for agonists of other nuclear receptor superfamily.