FIGURE 6.
Impact of vestibule mutations in hSERT on inhibitor potency. A, left, structure of the TCA-binding site in LeuT with imipramine bound (PDB code 2Q72). Right, overlay of homology model of hSERT with LeuT structure (shown in left panel) to show the equivalent site in hSERT. TM1 (blue) and TM3, TM6, EL4, and TM10 (pink) are shown. B, graphical summary of fold change (mean ± S.E.; n = 6-10) in potency of (S)-citalopram, imipramine, and clomipramine at hSERT mutants compared with WT hSERT. For comparison, the fold changes in potency for (S)-citalopram, imipramine, and clomipramine at S438T compared with WT hSERT are shown. Ki values and statistics are shown in supplemental Table S2. * indicates a significant change (p < 0.05) in Ki values.