(A) Detailed interactions between PW0464 (cyan) and DRD1 (marine) shown in extracellular view (left panel) or side view (right panel). PW0464 occupies the same hydrophobic OBP as dopamine but exhibits a different binding mode. Polar interactions are highlighted with black dotted lines. The ligand PW0464 forms potential polar interactions with D3.32-S5.42-S5.46 motif via the pyridine nitrogen and difluoromethoxy group and retains the putative hydrogen bonding with N2926.55 and an additional direct interaction with K812.61.
(B) Diagram of ligand interactions between DRD1 and PW0464. The difluoromethoxy, pyridine (orange shade), phenoxy (gray shade), and pyrimidinedione groups (sky blue shade) are highlighted. Polar interactions are shown by the blue dashed lines.
(C) Effects of the D1033.32-S1985.42-S2025.46 mutants of DRD1 on PW0464-induced cAMP accumulation.
See also Figure S4 and Table S4.