A cation-pi interaction in the binding site of the glycine receptor is mediated by a phenylalanine residue

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

A cation-pi interaction in the binding site of the glycine receptor is mediated by a phenylalanine residue. / Pless, Stephan Alexander; Millen, Kat S; Hanek, Ariele P; Lynch, Joseph W; Lester, Henry A; Lummis, Sarah C R; Dougherty, Dennis A.

In: The Journal of neuroscience : the official journal of the Society for Neuroscience, Vol. 28, No. 43, 22.10.2008, p. 10937-42.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Pless, SA, Millen, KS, Hanek, AP, Lynch, JW, Lester, HA, Lummis, SCR & Dougherty, DA 2008, 'A cation-pi interaction in the binding site of the glycine receptor is mediated by a phenylalanine residue', The Journal of neuroscience : the official journal of the Society for Neuroscience, vol. 28, no. 43, pp. 10937-42. https://doi.org/10.1523/JNEUROSCI.2540-08.2008

APA

Pless, S. A., Millen, K. S., Hanek, A. P., Lynch, J. W., Lester, H. A., Lummis, S. C. R., & Dougherty, D. A. (2008). A cation-pi interaction in the binding site of the glycine receptor is mediated by a phenylalanine residue. The Journal of neuroscience : the official journal of the Society for Neuroscience, 28(43), 10937-42. https://doi.org/10.1523/JNEUROSCI.2540-08.2008

Vancouver

Pless SA, Millen KS, Hanek AP, Lynch JW, Lester HA, Lummis SCR et al. A cation-pi interaction in the binding site of the glycine receptor is mediated by a phenylalanine residue. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2008 Oct 22;28(43):10937-42. https://doi.org/10.1523/JNEUROSCI.2540-08.2008

Author

Pless, Stephan Alexander ; Millen, Kat S ; Hanek, Ariele P ; Lynch, Joseph W ; Lester, Henry A ; Lummis, Sarah C R ; Dougherty, Dennis A. / A cation-pi interaction in the binding site of the glycine receptor is mediated by a phenylalanine residue. In: The Journal of neuroscience : the official journal of the Society for Neuroscience. 2008 ; Vol. 28, No. 43. pp. 10937-42.

Bibtex

@article{000bdd831ee94466aaabe3eef0edfbbb,
title = "A cation-pi interaction in the binding site of the glycine receptor is mediated by a phenylalanine residue",
abstract = "Cys-loop receptor binding sites characteristically contain many aromatic amino acids. In nicotinic ACh and 5-HT3 receptors, a Trp residue forms a cation-pi interaction with the agonist, whereas in GABA(A) receptors, a Tyr performs this role. The glycine receptor binding site, however, contains predominantly Phe residues. Homology models suggest that two of these Phe side chains, Phe159 and Phe207, and possibly a third, Phe63, are positioned such that they could contribute to a cation-pi interaction with the primary amine of glycine. Here, we test this hypothesis by incorporation of a series of fluorinated Phe derivatives using unnatural amino acid mutagenesis. The data reveal a clear correlation between the glycine EC(50) value and the cation-pi binding ability of the fluorinated Phe derivatives at position 159, but not at positions 207 or 63, indicating a single cation-pi interaction between glycine and Phe159. The data thus provide an anchor point for locating glycine in its binding site, and demonstrate for the first time a cation-pi interaction between Phe and a neurotransmitter.",
keywords = "Amino Acids, Aromatic, Animals, Binding Sites, Cations, Glycine, Humans, Microinjections, Models, Molecular, Mutagenesis, Site-Directed, Oocytes, Phenylalanine, Protein Binding, Protein Conformation, Protein Structure, Secondary, Radioligand Assay, Receptors, Glycine, Structure-Activity Relationship, Xenopus laevis",
author = "Pless, {Stephan Alexander} and Millen, {Kat S} and Hanek, {Ariele P} and Lynch, {Joseph W} and Lester, {Henry A} and Lummis, {Sarah C R} and Dougherty, {Dennis A}",
year = "2008",
month = oct,
day = "22",
doi = "10.1523/JNEUROSCI.2540-08.2008",
language = "English",
volume = "28",
pages = "10937--42",
journal = "The Journal of neuroscience : the official journal of the Society for Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "43",

}

RIS

TY - JOUR

T1 - A cation-pi interaction in the binding site of the glycine receptor is mediated by a phenylalanine residue

AU - Pless, Stephan Alexander

AU - Millen, Kat S

AU - Hanek, Ariele P

AU - Lynch, Joseph W

AU - Lester, Henry A

AU - Lummis, Sarah C R

AU - Dougherty, Dennis A

PY - 2008/10/22

Y1 - 2008/10/22

N2 - Cys-loop receptor binding sites characteristically contain many aromatic amino acids. In nicotinic ACh and 5-HT3 receptors, a Trp residue forms a cation-pi interaction with the agonist, whereas in GABA(A) receptors, a Tyr performs this role. The glycine receptor binding site, however, contains predominantly Phe residues. Homology models suggest that two of these Phe side chains, Phe159 and Phe207, and possibly a third, Phe63, are positioned such that they could contribute to a cation-pi interaction with the primary amine of glycine. Here, we test this hypothesis by incorporation of a series of fluorinated Phe derivatives using unnatural amino acid mutagenesis. The data reveal a clear correlation between the glycine EC(50) value and the cation-pi binding ability of the fluorinated Phe derivatives at position 159, but not at positions 207 or 63, indicating a single cation-pi interaction between glycine and Phe159. The data thus provide an anchor point for locating glycine in its binding site, and demonstrate for the first time a cation-pi interaction between Phe and a neurotransmitter.

AB - Cys-loop receptor binding sites characteristically contain many aromatic amino acids. In nicotinic ACh and 5-HT3 receptors, a Trp residue forms a cation-pi interaction with the agonist, whereas in GABA(A) receptors, a Tyr performs this role. The glycine receptor binding site, however, contains predominantly Phe residues. Homology models suggest that two of these Phe side chains, Phe159 and Phe207, and possibly a third, Phe63, are positioned such that they could contribute to a cation-pi interaction with the primary amine of glycine. Here, we test this hypothesis by incorporation of a series of fluorinated Phe derivatives using unnatural amino acid mutagenesis. The data reveal a clear correlation between the glycine EC(50) value and the cation-pi binding ability of the fluorinated Phe derivatives at position 159, but not at positions 207 or 63, indicating a single cation-pi interaction between glycine and Phe159. The data thus provide an anchor point for locating glycine in its binding site, and demonstrate for the first time a cation-pi interaction between Phe and a neurotransmitter.

KW - Amino Acids, Aromatic

KW - Animals

KW - Binding Sites

KW - Cations

KW - Glycine

KW - Humans

KW - Microinjections

KW - Models, Molecular

KW - Mutagenesis, Site-Directed

KW - Oocytes

KW - Phenylalanine

KW - Protein Binding

KW - Protein Conformation

KW - Protein Structure, Secondary

KW - Radioligand Assay

KW - Receptors, Glycine

KW - Structure-Activity Relationship

KW - Xenopus laevis

U2 - 10.1523/JNEUROSCI.2540-08.2008

DO - 10.1523/JNEUROSCI.2540-08.2008

M3 - Journal article

C2 - 18945901

VL - 28

SP - 10937

EP - 10942

JO - The Journal of neuroscience : the official journal of the Society for Neuroscience

JF - The Journal of neuroscience : the official journal of the Society for Neuroscience

SN - 0270-6474

IS - 43

ER -

ID: 122597853