Fig. 3: Cryo-EM structure of SERT:IMI:VLZ complex.
From: The antidepressant drug vilazodone is an allosteric inhibitor of the serotonin transporter
a The overall reconstruction of the SERT:15B8-Fab:IMI:VLZ complex at 3.65 Å (PDB: 7LWD). Right panel shows the zoomed allosteric and central sites. SERT is colored in light blue and the 15B8 Fab is shown in green. IMI and VLZ densities are shown in yellow and red, respectively. b Surface representation of the outward-open structure of SERT, viewed parallel to the membrane. The open extracellular pathway and the closed intracellular pathway are displayed. IMI and VLZ are shown as ball sticks. c Zoomed view of the IMI (yellow) binding site. IMI is shown fit into a density feature at the S1 site with subsite A, B, and C and the involved SERT backbone structures (light blue) annotated. Parts of SERT have been removed for clarity. d VLZ (red) is shown fit into a density feature at the allosteric site with the central SERT backbone structures annotated. Parts of SERT have been removed for clarity. e Comparison of the IMI (yellow) binding pose with the binding poses for S-CIT (light magenta, PDB code:5I73) and paroxetine (gray, PDB code:5I6X) within the S1 site. The main chain position of SERT from the IMI:VLZ complex is shown in light blue. f Comparison of VLZ (red) with S-CIT (light magenta, PDB code:5I73) and Lu AF60097 (gray). The main chain position of SERT from the IMI:VLZ complex is shown in light blue.
