Figure 4: Functional correlation of the ivermectin/FXR interactions.
From: The antiparasitic drug ivermectin is a novel FXR ligand that regulates metabolism
(a–d) Molecular determinants of the interaction between FXR with ligand ivermectin. Overlays of the FXR–ivermectin structure (green) with the FXR–GW4064 (salmon red) structure, where ligand ivermectin is in yellow and GW4064 is in purple. The hydrophobic interactions and hydrogen bonds are shown with lines and arrows, respectively. The potential hydrophobic interactions and hydrogen bonds, if the corresponding mutations are made as indicated in e, are shown in dashed lines and dashed arrows, respectively. (e) Differential effects of mutations of key FXR residues on its transcriptional activity in response to ivermectin and GW4064 in cell-based reporter assays. COS-7 cells were cotransfected with plasmids encoding full-length wild-type (WT) FXR or FXR mutants as indicated in the figure, together with an EcRE luciferase reporter. The cells were treated with 0.5 μM ivermectin and GW4064, respectively. The dashed line indicates the activation level of WT FXR by ivermectin. Values are the means±s.e.m. of three independent experiments. *P<0.05, **P<0.01 versus vehicle, Student’s t-test.
