A single extracellular amino acid in Free Fatty Acid Receptor 2 defines antagonist species selectivity and G protein selection bias.

ABSTRACT: Free Fatty Acid Receptor 2 is a GPCR activated by short chain fatty acids produced in high levels in the lower gut by microbial fermentation of non-digestible carbohydrates. A major challenge in studying this receptor is that the mouse ortholog does not have significant affinity for antagonists that are able to block the human receptor. Docking of exemplar antagonists from two chemical series to homology models of both human and mouse Free Fatty Acid Receptor 2 suggested that a single lysine - arginine variation at the extracellular face of the receptor might provide the basis for antagonist selectivity and mutational swap studies confirmed this hypothesis. Extending these studies to agonist function indicated that although the lysine - arginine variation between human and mouse orthologs

SUBMITTER: Sergeev E 

PROVIDER: S-EPMC5653858 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature