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Multiple Tyrosine Residues Contribute to GABA Binding in the GABAC Receptor Binding Pocket

Overview of attention for article published in ACS Chemical Neuroscience, January 2012
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Title
Multiple Tyrosine Residues Contribute to GABA Binding in the GABAC Receptor Binding Pocket
Published in
ACS Chemical Neuroscience, January 2012
DOI 10.1021/cn200103n
Pubmed ID
Authors

Sarah C. R. Lummis, Neil J. Harrison, Jinti Wang, Jamie A. Ashby, Katherine S. Millen, Darren L. Beene, Dennis A. Dougherty

Abstract

The ligand binding site of Cys-loop receptors is dominated by aromatic amino acids. In GABA(C) receptors, these are predominantly tyrosine residues, with a number of other aromatic residues located in or close to the binding pocket. Here we examine the roles of these residues using substitution with both natural and unnatural amino acids followed by functional characterization. Tyr198 (loop B) has previously been shown to form a cation-π interaction with GABA; the current data indicate that none of the other aromatic residues form such an interaction, although the data indicate that both Tyr102 and Phe138 may contribute to stabilization of the positively charged amine of GABA. Tyr247 (loop C) was very sensitive to substitution and, combined with data from a model of the receptor, suggest a π-π interaction with Tyr241 (loop C); here again functional data show aromaticity is important. In addition the hydroxyl group of Tyr241 is important, supporting the presence of a hydrogen bond with Arg104 suggested by the model. At position Tyr102 (loop D) size and aromaticity are important; this residue may play a role in receptor gating and/or ligand binding. The data also suggest that Tyr167, Tyr200, and Tyr208 have a structural role while Tyr106, Trp246, and Tyr251 are not critical. Comparison of the agonist binding site "aromatic box" across the superfamily of Cys-loop receptors reveals some interesting parallels and divergences.

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Mendeley readers

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The data shown below were compiled from readership statistics for 21 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Austria 2 10%
Unknown 19 90%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 8 38%
Researcher 7 33%
Other 1 5%
Student > Master 1 5%
Student > Doctoral Student 1 5%
Other 2 10%
Unknown 1 5%
Readers by discipline Count As %
Agricultural and Biological Sciences 8 38%
Chemistry 5 24%
Biochemistry, Genetics and Molecular Biology 2 10%
Pharmacology, Toxicology and Pharmaceutical Science 2 10%
Neuroscience 1 5%
Other 1 5%
Unknown 2 10%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 16 December 2011.
All research outputs
#20,656,161
of 25,373,627 outputs
Outputs from ACS Chemical Neuroscience
#2,303
of 2,748 outputs
Outputs of similar age
#203,900
of 250,257 outputs
Outputs of similar age from ACS Chemical Neuroscience
#20
of 23 outputs
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