Cited by 316Nicotinic Acetylcholine Receptors StudyReceptor Mechanisms and SignalingNeuroscience and Neuropharmacology Research

Cation−π Interactions in Ligand Recognition by Serotonergic (5-HT3A) and Nicotinic Acetylcholine Receptors: The Anomalous Binding Properties of Nicotine

Beene, Darren L., Brandt, Gabriel S., Zhong, Wenge, Zacharias, Niki M., Lester, Henry A., Dougherty, Dennis A.·2002·Biochemistry

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.

Integrity signals

Registry

Crossref · 10.1021/bi020266d

Cites

18 of 18 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Beene, D. L., Brandt, G. S., Zhong, W., Zacharias, N. M., Lester, H. A., & Dougherty, D. A.
Affiliations
California Institute of Technology (US)
Venue
Biochemistry
Published
2002-07-19
Volume
41
Issue
32
Pages
10262-10269
ISSN
  • 0006-2960 (ISSN-L)
  • 1520-4995
OpenAlex
W2004976660
Cited by
300
References
18
Citations by year
2026: 3 · 2025: 6 · 2024: 10 · 2023: 3 · 2022: 5 · 2021: 4 · 2020: 12 · 2019: 11 · 2018: 9 · 2017: 7 · 2016: 10 · 2015: 16 · 2014: 11 · 2013: 14 · 2012: 22
FWCI
6.74
Type
journal article
Language
en
Open access
closed
Locations
  • Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
  • CaltechAUTHORS (California Institute of Technology) (submittedVersion)
Funders
National Institute of Neurological Disorders and Stroke (NS34407, NS 11756, R01NS011756)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
cation-π interactions, 5-HT3A receptor, nicotinic acetylcholine receptors, nicotine binding, serotonin binding, tryptophan analogues, ligand-gated ion channels, ligand recognition, unnatural amino acid mutagenesis, ligand binding sites, acetylcholine binding, quaternary ammonium compounds
MeSH terms
Alkylation, Amino Acid Sequence, Animals, Binding Sites, Cations, Dose-Response Relationship, Drug, Female, Fluorine Radioisotopes, Ligands, Molecular Sequence Data, Nicotine, Pyridinium Compounds, Receptors, Nicotinic, Receptors, Serotonin, Serotonin, Tryptophan, Xenopus laevis, Mutagenesis, Site-Directed, Serotonin Receptor Agonists, Patch-Clamp Techniques, Amino Acid Substitution, Receptors, Serotonin, 5-HT3, Mice, Static Electricity

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review