title: Mutational analysis of G-protein coupled receptor--FFA2.
abstract: FFA2 (GPR43) is a receptor for short-chain fatty acids (SCFAs), acetate, and propionate. FFA2 is predominantly expressed in islets, a subset of immune cells, adipocytes, and the gastrointestinal tract which suggest a possible role in inflammatory and metabolic conditions. We have previously described the identification and characterization of novel phenylacetamides as allosteric agonists of FFA2. In the current study, we have investigated the molecular determinants contributing to receptor activation with the endogenous and synthetic ligands as well as allosteric interactions between these two sites. The mutational analysis revealed previously unidentified sites that may allosterically regulate orthosteric ligand's function as well as residues potentially important for the interactions between orthosteric and allosteric binding sites.
authors.affiliation: Amgen Inc., South San Francisco, CA 94080, USA.
authors.forename: Gayathri
authors.initials: G
authors.lastname: Swaminath
authors.forename: Peter
authors.initials: P
authors.lastname: Jaeckel
authors.forename: Qi
authors.initials: Q
authors.lastname: Guo
authors.forename: Mario
authors.initials: M
authors.lastname: Cardozo
authors.forename: Jennifer
authors.initials: J
authors.lastname: Weiszmann
authors.forename: Richard
authors.initials: R
authors.lastname: Lindberg
authors.forename: Yingcai
authors.initials: Y
authors.lastname: Wang
authors.forename: Ralf
authors.initials: R
authors.lastname: Schwandner
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D001665:Binding Sites; D004252:DNA Mutational Analysis; D057809:HEK293 Cells; D006801:Humans; D008024:Ligands; D016296:Mutagenesis; D011487:Protein Conformation; D011956:Receptors, Cell Surface / Q000819:agonists* / Q000737:chemistry / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled
chemical_list: D008024:Ligands; D011956:Receptors, Cell Surface; C473103:FFAR2 protein, human; D043562:Receptors, G-Protein-Coupled