Figure 4. Comparison of extended binding pockets (EBPs) between DRD1 and D2-like receptors.

(A) Structural comparison of the EBP in PW0464 (cyan)-bound DRD1 (sky blue) structure with that in bromocriptine (pale green)-bound DRD2 (orange) (PDB: 6VMS). The ligands PW0464 and bromocriptine are represented as sticks/spheres by corresponding colors, and the side chains of key residues of EBP are shown in sticks for both receptors.

(B) Surface representation and cut away view of the ligand binding pocket for PW0464-bound DRD1 structure (left panel) and bromocriptine-bound DRD2 structure (right panel). The ligand PW0464 was covered by the ECL2 region of DRD1.

(C) Structural representation of the EBPs in antagonist-bound D2-like receptors. Risperidone (blue sphere)-bound DRD2 (light orange) (left, PDB: 6CM4), eticlopride (warm pink sphere)-bound DRD3 (teal) (middle, PDB: 3PBL), and nemonapride (light orange sphere)-bound DRD4 (light blue) (right, PDB: 5WIU).

(D) Sequence alignment of two critical motifs of EBP in five dopaminergic receptors located in TM2, TM3, TM6, and TM7. The K^2.61-W^3.28-W^7.43 motifs of D1-like receptors are highlighted in red, whereas the N^6.55-F^7.35 pairs are highlighted in blue.

See also Figure S5 and Table S2.