Title |
Cation−π Interactions in Ligand Recognition by Serotonergic (5-HT3A) and Nicotinic Acetylcholine Receptors: The Anomalous Binding Properties of Nicotine †
|
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Published in |
Biochemistry, July 2002
|
DOI | 10.1021/bi020266d |
Pubmed ID | |
Authors |
Darren L. Beene, Gabriel S. Brandt, Wenge Zhong, Niki M. Zacharias, Henry A. Lester, Dennis A. Dougherty |
Abstract |
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. |
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Geographical breakdown
Country | Count | As % |
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United States | 2 | 2% |
Switzerland | 1 | <1% |
Netherlands | 1 | <1% |
United Kingdom | 1 | <1% |
South Africa | 1 | <1% |
Korea, Republic of | 1 | <1% |
Canada | 1 | <1% |
Unknown | 112 | 93% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 36 | 30% |
Researcher | 21 | 18% |
Student > Master | 12 | 10% |
Student > Bachelor | 12 | 10% |
Student > Doctoral Student | 7 | 6% |
Other | 19 | 16% |
Unknown | 13 | 11% |
Readers by discipline | Count | As % |
---|---|---|
Chemistry | 36 | 30% |
Agricultural and Biological Sciences | 29 | 24% |
Biochemistry, Genetics and Molecular Biology | 13 | 11% |
Pharmacology, Toxicology and Pharmaceutical Science | 6 | 5% |
Neuroscience | 5 | 4% |
Other | 17 | 14% |
Unknown | 14 | 12% |