In silico identification of a β₂-adrenoceptor allosteric site that selectively augments canonical β₂AR-Gs signaling and function.

ABSTRACT: Activation of β₂-adrenoceptors (β₂ARs) causes airway smooth muscle (ASM) relaxation and bronchodilation, and β₂AR agonists (β-agonists) are front-line treatments for asthma and other obstructive lung diseases. However, the therapeutic efficacy of β-agonists is limited by agonist-induced β₂AR desensitization and noncanonical β₂AR signaling involving β-arrestin that is shown to promote asthma pathophysiology. Accordingly, we undertook the identification of an allosteric site on β₂AR that could modulate the activity of β-agonists to overcome these limitations. We employed the site identification by ligand competitive saturation (SILCS) computational method to comprehensively map the entire 3D structure of in silico-generated β<

SUBMITTER: Shah SD 

PROVIDER: S-EPMC9894167 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature