A Cation-π Interaction in the Binding Site of the Glycine Receptor Is Mediated by a Phenylalanine Residue
| Autor: | Henry A. Lester, Kat S. Millen, Ariele P. Hanek, Stephan A. Pless, Dennis A. Dougherty, Sarah C. R. Lummis, Joseph W. Lynch |
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| Jazyk: | angličtina |
| Rok vydání: | 2008 |
| Předmět: |
Models
Molecular Microinjections Stereochemistry Protein Conformation Phenylalanine Glycine Receptor Binding Glycine Article Protein Structure Secondary Cation–pi interaction chemistry.chemical_compound Amino Acids Aromatic Radioligand Assay Structure-Activity Relationship Xenopus laevis Receptors Glycine Cations Aromatic amino acids Animals Humans Binding site Glycine receptor chemistry.chemical_classification Glycine cleavage system Binding Sites Chemistry General Neuroscience Amino acid Biochemistry Mutagenesis Site-Directed Oocytes Caltech Library Services Protein Binding |
| Popis: | Cys-loop receptor binding sites characteristically contain many aromatic amino acids. In nicotinic ACh and 5-HT3receptors, a Trp residue forms a cation-π interaction with the agonist, whereas in GABAAreceptors, 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-π 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 EC50value and the cation-π binding ability of the fluorinated Phe derivatives at position 159, but not at positions 207 or 63, indicating a single cation-π 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-π interaction between Phe and a neurotransmitter. |
| Databáze: | OpenAIRE |
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