Structural basis for ligand recognition of the neuropeptide Y Y₂ receptor.

ABSTRACT: The human neuropeptide Y (NPY) Y₂ receptor (Y₂R) 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 Å 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

SUBMITTER: Tang T 

PROVIDER: S-EPMC7854658 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature