| Description |
The human neuropeptide Y Y2 receptor plays essential roles in food intake, bone formation and mood regulation, and has been considered an important drug target for obesity and anxiety. However, development of drugs targeting Y2R remains challenging with no success in clinical application yet. Here, we report the crystal structure of Y2R bound to a selective antagonist JNJ 31020028 at 2.8 angstrom resolution. The structure reveals molecular details of the ligand binding mode of Y2R. Combined with mutagenesis studies, the Y2R structure provides insights into key factors that define antagonistic activity of diverse antagonists. Comparison with the previously determined antagonist bound Y1R structures identified receptor ligand interactions that play different roles in modulating receptor acti vation and mediating ligand selectivity. |