title: Role of conserved serine residues in the interaction of agonists with D3 dopamine receptors.
abstract: To understand the role of conserved serine residues in the fifth transmembrane domain (Ser192, Ser193, and Ser196) of the D3 dopamine receptor, these have been mutated individually to alanine, and the ligand binding properties of the mutant receptors have been evaluated. The mutations had little or no effect on the binding of the antagonist spiperone and the agonist quinpirole, indicating that the overall conformation of the receptor was unaffected. The binding of dopamine and 7-hydroxydipropylaminotetralin, agonists containing hydroxyl groups, was, however, of lower affinity for the Ser192 mutation but unaffected by the other mutations (Ser193 and Ser196). Therefore, for the agonists tested, the hydroxyl groups interact exclusively with Ser192.
authors.affiliation: Research School of Biosciences, The University, Canterbury, England.
authors.forename: N
authors.initials: N
authors.lastname: Sartania
authors.forename: P G
authors.initials: PG
authors.lastname: Strange
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001665:Binding Sites; D001667:Binding, Competitive; D002460:Cell Line; D017124:Conserved Sequence; D004298:Dopamine / Q000378:metabolism*; D018491:Dopamine Agonists / Q000378:metabolism*; D006801:Humans; D007668:Kidney; D007700:Kinetics; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D017448:Receptors, Dopamine D2 / Q000737:chemistry* / Q000378:metabolism*; D050637:Receptors, Dopamine D3; D012694:Serine; D013134:Spiperone / Q000493:pharmacokinetics; D013764:Tetrahydronaphthalenes / Q000378:metabolism; D014316:Tritium
chemical_list: C493593:DRD3 protein, human; D018491:Dopamine Agonists; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D013764:Tetrahydronaphthalenes; D014316:Tritium; D012694:Serine; D013134:Spiperone; C031349:7-hydroxy-2-N,N-dipropylaminotetralin; D004298:Dopamine