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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. https://resolver.caltech.edu/CaltechAUTHORS:20200424-080629607

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Abstract

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
https://doi.org/10.1016/j.chembiol.2005.06.012DOIArticle
ORCID:
AuthorORCID
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).
Funders:
Funding AgencyGrant Number
Wellcome TrustUNSPECIFIED
Medical Research Council (UK)UNSPECIFIED
NIHNS11756
NIHNS34407
Issue or Number:9
Record Number:CaltechAUTHORS:20200424-080629607
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20200424-080629607
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, https://doi.org/10.1016/j.chembiol.2005.06.012. (http://www.sciencedirect.com/science/article/pii/S1074552105002024)
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:102766
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:24 Apr 2020 15:24
Last Modified:24 Apr 2020 15:24

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