Fig. 1 | Nature Communications

Fig. 1

From: The anthelmintic praziquantel is a human serotoninergic G-protein-coupled receptor ligand

Fig. 1

Resolution of stereoselective (R)-PZQ interaction with human 5-HT2BR. Structures of the PZQ enantiomers: active, a antischistocidal (R)-PZQ (top, red) and b (S)-PZQ (bottom, blue). c Docking poses of R-PZQ (light red) and S-PZQ (light blue) in the human 5HT2BR. Both isomers of PZQ dock favorably within the orthosteric pocket of the 5HT2BR crystal structure (Protein Databank Code: 5TVN). The R-isomer shows a better predicted binding score by 0.6 kcal/mole partially due to a more favorable hydrogen bond with the backbone NH group of L209. d Displacement of 3H-LSD binding at human 5-HT2BR by racemic PZQ ((±)-PZQ 10 µM, purple), (R)-PZQ (5 µM, red) and (S)-PZQ (5 µM, blue) in the PDSP primary screen (n = 5 for all measurements). e Complete binding displacement curves for 3H-LSD displacement at human 5-HT2BR for SB206553 (black) and (±)-PZQ (purple, n = 5 for both ligands). f Functional Assays. Ca2+ flux assays showing responses from fluo-4 loaded Flp-In T-REx cells stably expressing 5-HT2AR, 5-HT2BR, or 5-HT2CR at indicated concentrations of (±)-PZQ (purple, top), (R)-PZQ (red, middle) and (S)-PZQ (blue, bottom; n = 3 for each concentration) in cells expressing 5-HT2AR, 5-HT2BR, or 5-HT2CR

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