Fig. 1: Characterization of VLZ binding to SERT WT and S1 mutants.
From: The antidepressant drug vilazodone is an allosteric inhibitor of the serotonin transporter
a Inhibition potency of VLZ (black) and S-CIT (brown) compared to 5-HT (gray). The affinity for VLZ is 5-fold higher than for S-CIT in inhibiting [3H]5-HT transport with Ki values of 1.06 [0.90; 1.25] and 5.21 [4.19; 6.48] nM, respectively (n = 6). b Equilibrium binding inhibition for S-CIT and VLZ displacement of [3H]S-CIT. The Ki for VLZ is 7-fold higher than for S-CIT (0.68 [0.56; 0.83] and 5.13 [2.85; 3.76] nM, respectively). c, d The affinity for S-CIT but not VLZ is affected by mutations in the SERT S1 site. S-CIT binding is decreased by 7- and 192- and 625-fold by the mutations Y95F (purple), I172M (blue) and S438T (green), respectively relative to WT (dotted line of data in a). The mutations do not significantly affect the affinity for VLZ. VMAX, KM, Ki, and n-values for 5-HT, S-CIT, and VLZ binding to SERT WT and S1 mutants are shown in the Supplementary Table 1. Experiments are performed in triplicates on intact COS7 cells transiently expressing SERT WT or mutants. Data are shown as means ± S.E. (error bars), n = 4–17. Source data are provided as a Source Data file.
