title: A cation-pi binding interaction with a tyrosine in the binding site of the GABAC receptor.
abstract: GABA(C) (rho) receptors are members of the Cys-loop superfamily of neurotransmitter receptors, which includes nicotinic acetylcholine (nACh), 5-HT(3), and glycine receptors. As in other members of this family, the agonist binding site of GABA(C) receptors is rich in aromatic amino acids, but while other receptors bind agonist through a cation-pi interaction to a tryptophan, the GABA(C) binding site has tyrosine at the aligning positions. Incorporating a series of tyrosine derivatives at position 198 using unnatural amino acid mutagenesis reveals a clear correlation between the cation-pi binding ability of the side chain and EC(50) for receptor activation, thus demonstrating a cation-pi interaction between a tyrosine side chain and a neurotransmitter. Comparisons among four homologous receptors show variations in cation-pi binding energies that reflect the nature of the cationic center of the agonist.
authors.affiliation: Department of Biochemistry, University of Cambridge, UK.
authors.forename: Sarah C R
authors.initials: SC
authors.lastname: Lummis
authors.forename: Darren
authors.initials: D
authors.lastname: L Beene
authors.forename: Neil J
authors.initials: NJ
authors.lastname: Harrison
authors.forename: Henry A
authors.initials: HA
authors.lastname: Lester
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Dougherty
mesh_terms: D019943:Amino Acid Substitution; D001665:Binding Sites; D002412:Cations; D008958:Models, Molecular; D016296:Mutagenesis; D011487:Protein Conformation; D018079:Receptors, GABA / Q000737:chemistry / Q000378:metabolism*; D014443:Tyrosine / Q000378:metabolism*
chemical_list: D002412:Cations; C087200:GABA-C receptor; D018079:Receptors, GABA; D014443:Tyrosine