Cation−π Interactions in Ligand Recognition by Serotonergic (5-HT3A) and Nicotinic Acetylcholine Receptors: The Anomalous Binding Properties of Nicotine
Copyright policy )Cation−π Interactions in Ligand Recognition by Serotonergic (5-HT3A) and Nicotinic Acetylcholine Receptors: The Anomalous Binding Properties of Nicotine
A series of tryptophan analogues has been introduced into the binding site regions of two ion channels, the ligand-gated nicotinic acetylcholine and serotonin 5-HT(3A) receptors, using unnatural amino acid mutagenesis and heterologous expression in Xenopus oocytes. A cation-pi interaction between serotonin and Trp183 of the serotonin channel 5-HT(3A)R is identified for the first time, precisely locating the ligand-binding site of this receptor. The energetic contribution of the observed cation-pi interaction between a tryptophan and the primary ammonium ion of serotonin is estimated to be approximately 4 kcal/mol, while the comparable interaction with the quaternary ammonium of acetylcholine is approximately 2 kcal/mol. The binding mode of nicotine to the nicotinic receptor of mouse muscle is examined by the same technique and found to differ significantly from that of the natural agonist, acetylcholine.
- California Institute of Technology United States
- Amgen (United States) United States
570, Fluorine Radioisotopes, Nicotine, Serotonin, Binding Sites, Patch-Clamp Techniques, Alkylation, Dose-Response Relationship, Drug, Molecular Sequence Data, Pyridinium Compounds, Receptors, Nicotinic, 540, Ligands, Mice, Amino Acid Substitution, Cations, Receptors, Serotonin, Mutagenesis, Site-Directed, Animals, Female, Amino Acid Sequence, Receptors, Serotonin, 5-HT3
570, Fluorine Radioisotopes, Nicotine, Serotonin, Binding Sites, Patch-Clamp Techniques, Alkylation, Dose-Response Relationship, Drug, Molecular Sequence Data, Pyridinium Compounds, Receptors, Nicotinic, 540, Ligands, Mice, Amino Acid Substitution, Cations, Receptors, Serotonin, Mutagenesis, Site-Directed, Animals, Female, Amino Acid Sequence, Receptors, Serotonin, 5-HT3
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