Figure 5

Homology models of SERT homologues and paroxetine (PXT) poses from the largest cluster for (a) hsSERT-WT (14 poses), (b) hsSERT-A169D (9 poses), (c) ggSERT-WT (8 poses) and (d) dmSERT (6 poses). Docked paroxetine is colored as in Fig. 2. Transmembrane helices are illustrated as transparent ribbons and colored as follows: TM1 (salmon), TM3 (light orange), TM6 (pale green), TM8 (blue) and TM10 (magenta). For all complexes, oxygen and nitrogen atoms are red and blue, respectively, while carbon atoms are the same color from the helix to which they belong. Carbon atoms from amino acids targeted for mutagenesis, however, are yellow and these residues are depicted as thicker sticks. Residues depicted as the thickest sticks , with side chain atoms in partially transparent spheres, are those which, when mutated, had the greatest impact on paroxetine potency (A169D, D209A and D164A in hsSERT, ggSERT and dmSERT, respectively). Sodium and chloride ions are shown as purple and green spheres, respectively. Note that S438 and its equivalents in dmSERT (S429) and ggSERT (S478) are behind the docked paroxetine models and thus not visible in all panels. Also note that Y216 (equivalent to Y176 in hsSERT and Y171 in dmSERT) is behind the docked paroxetine poses in the ggSERT image (panel c).