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• W4367596527 abstract "GPR61 is a biogenic amine receptor-related orphan GPCR associated with phenotypes relating to appetite and thus, is of interest as a druggable target to treat disorders of metabolism and body weight, such as obesity and cachexia. To date, lack of structural information or a known biological ligand or tool compound has hindered comprehensive efforts to study its structure and function. Here, we report the first ever structural characterization of GPR61, in both its active-like complex with heterotrimeric G protein and in its inactive state. Moreover, we report the discovery of a potent and selective small-molecule inverse agonist against GPR61 and structural elucidation of its unprecedented allosteric site and mode of action. These findings offer key mechanistic insights into an orphan GPCR, while providing both a new structural framework and tool compound to support further studies of GPR61 function and modulation." @default.
• W4367596527 created "2023-05-02" @default.
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• W4367596527 date "2023-05-01" @default.
• W4367596527 modified "2023-09-25" @default.
• W4367596527 title "An inverse agonist of orphan receptor GPR61 reveals a novel allosteric mechanism" @default.
• W4367596527 doi "https://doi.org/10.1101/2023.05.01.538732" @default.
• W4367596527 hasPublicationYear "2023" @default.
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