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- W4241434933 endingPage "1287" @default.
- W4241434933 startingPage "1283" @default.
- W4241434933 abstract "Positive reinforcement in a GPCR Many drug discovery efforts focus on G protein–coupled receptors (GPCRs), a class of receptors that regulate many physiological processes. An exemplar is the β 2 -adrenergic receptor (β 2 AR), which is targeted by both blockers and agonists to treat cardiovascular and respiratory diseases. Most GPCR drugs target the primary (orthosteric) ligand binding site, but binding at allosteric sites can modulate activation. Because such allosteric sites are less conserved, they could possibly be targeted more specifically. Liu et al. report the crystal structure of β 2 AR bound to both an orthosteric agonist and a positive allosteric modulator that increases receptor activity. The structure suggests why the modulator compound is selective for β 2 AR over the closely related β 1 AR. Furthermore, the structure reveals that the modulator acts by enhancing orthosteric agonist binding and stabilizing the active conformation of the receptor. Science , this issue p. 1283" @default.
- W4241434933 created "2022-05-12" @default.
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- W4241434933 date "2019-06-28" @default.
- W4241434933 modified "2023-10-17" @default.
- W4241434933 title "Mechanism of β <sub>2</sub> AR regulation by an intracellular positive allosteric modulator" @default.
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- W4241434933 doi "https://doi.org/10.1126/science.aaw8981" @default.
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