Fig. 6: Effect of SERT S2 mutants on VLZ allosteric potency.
From: The antidepressant drug vilazodone is an allosteric inhibitor of the serotonin transporter
a Zoomed interactions between VLZ and SERT. Schematics are generated by LIGPLOT + 1.4. Each eyelash motif indicates a hydrophobic contact. b Effect of mutating residues in the S2 site on allosteric potency for VLZ. Point mutation of residues, shown in the cryo-EM structure to interact with VLZ, all significantly (P < 0.001, one-way ANOVA with Tukey’s multiple comparisons test) decreases its allosteric potency to various degrees relative to SERT WT (dotted line, data shown in Fig. 2b). See allosteric potencies for SERT WT and mutants in Table 1. Experiments are performed on membrane preparations from COS-7 cells transiently expressing the indicated SERT mutants. Data are shown as means ± S.E. (error bars), n = 3–10. Wild-type is shown with a black dotted line. Allosteric site mutants are shown using colored symbols and solid lines defined in the legend. See Table 1 for quantitative data including allosteric potency and n-value for the individual experiments. Source data are provided as a Source Data file.
