Extended Data Fig. 4: Ligand binding pocket of 5-HT5AR.
From: Inactive and active state structures template selective tools for the human 5-HT5A receptor
a-b, Two views of the superposition of ligands AS2674723, 5-CT, lisuride, and methylergometrine in the 5-HT5AR binding site. The hydrogen bonds between T126 and three agonists are shown as dashed lines in the same color as the corresponding ligand, respectively. The positions of EBP1 and EBP2 are also indicated by the purple- and salmon-shaded ovals, respectively. c, Displacement of waters in the binding pocket of the apo 5-HT1AR-Gi complex structure (PDB: 7E2X) compared with the water molecule in the 5-CT bound structure. d, The representative density map of E305 in the 5-CT bound 5-HT5AR structure. e-g, cryo-EM maps of T126 and three agonists. The distances are indicated by the dashed lines. h. Structural alignment of the ligand-binding pockets of three agonist-bound 5-HT5AR complexes. i. Binding affinities of 5-HT and 5-CT to all the members of the human serotonin receptor family from the Ki database of PDSP (https://pdsp.unc.edu/databases/kidb.php). Data represent mean ± SEM of N = 1-10 replicates based on the source from the Ki database.
