Fig. 3: Unique features of the D1R ligand binding pocket.
From: Crystal structure of dopamine D1 receptor in complex with G protein and a non-catechol agonist
a Sequence alignment of aminergic receptors at ECL2, starting from the conserved cysteine, as well as 7.43 position (Ballesteros–Weinstein numbering). The residues at cysteine+2, cysteine+4 and 7.43 positions are highlighted, as they are unique in D1R/D5R. b The side chain orientations of the +2 residues (position indicated by dashed line) on ECL2, counting from the conserved disulfide bond forming cysteine residue. Compound 1 and Ser188 (cysteine+2 residue), L190 (cysteine+4 residue) of D1R, as well as all disulfide bonds are shown in stick, while cysteine+2 residues on other aminergic receptors are shown in line. D1R: green, Compound 1: lime; β2AR, gray (PDB ID: 4LDO); D2R: orange (PDB ID: 6VMS); 5-HT2C, magenta (PDB ID: 6BQG); 5-HT1B, yellow (PDB ID: 4IAR); b1AR, purple (PDB ID: 2Y03); D4R, cyan (PDB ID: 5WIV); D3R, blue (PDB ID: 3PBL); 5-HT2B, dark green (PDB ID: 4IB4). c Trp3217.43 is a unique feature in the D1R orthosteric site. D1R structure is aligned with 5-HT2B bound to ergotamine (dark green, PDB ID: 4IB4) and LSD (hot pink, PDB ID: 5TVN), and D2R bound to bromocriptine (orange, PDB ID: 6VMS). The Van der Waals radius of Trp3217.43 side chain is shown in sphere.
