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- W3128156728 abstract "Abstract The human neuropeptide Y (NPY) Y 2 receptor (Y 2 R) 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 Y 2 R remains challenging with no success in clinical application yet. Here, we report the crystal structure of Y 2 R bound to a selective antagonist JNJ-31020028 at 2.8 Å resolution. The structure reveals molecular details of the ligand-binding mode of Y 2 R. Combined with mutagenesis studies, the Y 2 R structure provides insights into key factors that define antagonistic activity of diverse antagonists. Comparison with the previously determined antagonist-bound Y 1 R structures identified receptor-ligand interactions that play different roles in modulating receptor activation and mediating ligand selectivity. These findings deepen our understanding about molecular mechanisms of ligand recognition and subtype specificity of NPY receptors, and would enable structure-based drug design." @default.
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- W3128156728 date "2021-02-02" @default.
- W3128156728 modified "2023-10-15" @default.
- W3128156728 title "Structural basis for ligand recognition of the neuropeptide Y Y2 receptor" @default.
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- W3128156728 doi "https://doi.org/10.1038/s41467-021-21030-9" @default.
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