Dopamine D1 receptor mutagenesis: role of amino acids in agonist and antagonist binding.
We investigated the role of amino acids, by site-directed mutagenesis, in five of the seven transmembrane regions of the human dopamine D1 receptor. The results demonstrate a role for an aspartic acid (Asp70) in transmembrane 2 mediating the sodium ion effect on receptor conformation. Amino acids residues in transmembrane 3 and 5 are important for optimum dopamine binding to the receptor. Mutant receptors involving amino acids in transmembrane 7 suggest that binding sites for agonists and antagonists have distinct binding determinants within the dopamine D1 receptor.
Tomic
M
M
Department of Pharmacology, University of Toronto, Ontario, Canada.
Seeman
P
P
George
S R
SR
O'Dowd
B F
BF
D000595:Amino Acid Sequence; D000818:Animals; D001552:Benzazepines / Q000378:metabolism; D001665:Binding Sites; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008565:Membrane Proteins / Q000737:chemistry; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D017434:Protein Structure, Tertiary; D011954:Receptors, Dopamine / Q000737:chemistry* / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship
D001552:Benzazepines; D008565:Membrane Proteins; D011954:Receptors, Dopamine; D011994:Recombinant Proteins; D004298:Dopamine