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A Cation-π Binding Interaction with a Tyrosine in the Binding Site of the GABA_C Receptor

Lummis, Sarah C. R. and Beene, Darren L. and Harrison, Neil J. and Lester, Henry A. and Dougherty, Dennis A. (2005) A Cation-π Binding Interaction with a Tyrosine in the Binding Site of the GABA_C Receptor. Chemistry and Biology, 12 (9). pp. 993-997. ISSN 1074-5521. doi:10.1016/j.chembiol.2005.06.012.

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GABA_C (ρ) receptors are members of the Cys-loop superfamily of neurotransmitter receptors, which includes nicotinic acetylcholine (nACh), 5-HT₃, 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-π 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-π binding ability of the side chain and EC₅₀ for receptor activation, thus demonstrating a cation-π interaction between a tyrosine side chain and a neurotransmitter. Comparisons among four homologous receptors show variations in cation-π binding energies that reflect the nature of the cationic center of the agonist.

Item Type:Article
Related URLs:
URLURL TypeDescription
Lummis, Sarah C. R.0000-0001-9410-9805
Lester, Henry A.0000-0002-5470-5255
Dougherty, Dennis A.0000-0003-1464-2461
Additional Information:© 2005 Elsevier Ltd. Received 22 April 2005, Revised 27 June 2005, Accepted 28 June 2005, Available online 23 September 2005. We would like to thank The Wellcome Trust (S.C.R.L. is a Wellcome Trust Senior Research Fellow in Basic Biomedical Science), the Medical Research Council (a studentship to N.J.H.), and the U.S. National Institutes of Health (NS11756, NS34407).
Funding AgencyGrant Number
Medical Research Council (UK)UNSPECIFIED
Issue or Number:9
Record Number:CaltechAUTHORS:20200424-080629607
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Official Citation:Sarah C.R. Lummis, Darren L. Beene, Neil J. Harrison, Henry A. Lester, Dennis A. Dougherty, A Cation-π Binding Interaction with a Tyrosine in the Binding Site of the GABAC Receptor, Chemistry & Biology, Volume 12, Issue 9, 2005, Pages 993-997, ISSN 1074-5521, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102766
Deposited By: Tony Diaz
Deposited On:24 Apr 2020 15:24
Last Modified:16 Nov 2021 18:15

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