Fig. 2: Characterization of the orthosteric ligand pocket.
From: Structural insights into lipid chain-length selectivity and allosteric regulation of FFA2
a Chemical structure of TUG-1375. b–d Overall structure of FFA2 bound to TUG-1375 (b), and enlarged views of the ligand pocket focused on TUG-1375 (c, d). Amino acid numbering and Ballesteros–Weinstein numbering22 for FFA2 are indicated. e–g Mutagenesis analysis of the TUG-1375-binding site using the TGFα shedding assay. The effect on the potency of TUG-1375 (e), propionate (f), and butyrate (g) was evaluated by pEC50 values. The pEC50 values were normalized by that of WT with similar expression levels (∆pEC50 values) (See also Supplementary Fig. 3a). NA represents parameters not available owing to a lack of ligand response. Bars and error bars represent the mean and SEM, respectively, of three independent experiments, each performed in duplicate. ** represents p < 0.01 with one-way ANOVA followed by Dunnett’s test for multiple comparison analysis with reference to WT. ns, not significantly different between the groups. See also the Source Data file for additional statistics and exact p-values.
