PT  - JOURNAL ARTICLE
AU  - Guan, X M
AU  - Peroutka, S J
AU  - Kobilka, B K
TI  - Identification of a single amino acid residue responsible for the binding of a class of beta-adrenergic receptor antagonists to 5-hydroxytryptamine1A receptors.
DP  - 1992 Apr 01
TA  - Molecular Pharmacology
PG  - 695--698
VI  - 41
IP  - 4
4099  - http://molpharm.aspetjournals.org/content/41/4/695.short
4100  - http://molpharm.aspetjournals.org/content/41/4/695.full
SO  - Mol Pharmacol1992 Apr 01; 41
AB  - The 5-hydroxytryptamine1A (5-HT1A) receptor can bind certain beta-adrenergic receptor antagonists, such as pindolol, with high affinity. Such pharmacological cross-reactivity suggests a structural similarity in the ligand binding site between the two receptors. To identify this structural entity, we mutated Asn385 in the seventh transmembrane domain of the human 5-HT1A receptor, based on the observation that this residue is conserved in all 5-HT1A and beta-adrenergic receptors of different species but is absent in all other cloned guanine nucleotide-binding protein-coupled receptors. This single point mutation (Asn385 to valine) causes a highly selective decrease in the affinity of pindolol and other aryloxyalkylamines for the mutant receptor (about 100-fold), while producing only minor changes in the binding of other 5-HT agonists and antagonists. The results provide direct evidence that Asn385 is responsible for the high affinity interaction between 5-HT1A receptors and aryloxyalkylamine beta-adrenergic antagonists but is not required for the binding of other chemical classes of ligands.