ArticleBritish journal of pharmacology2003
A structural model of agonist binding to the alpha3beta4 neuronal nicotinic receptor.
Article in British journal of pharmacology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 54 citations in OpenAlex.
- Partial Agonist Activity of Neonicotinoids on Rat Nicotinic Receptors: Consequences over Epinephrine Secretion and In Vivo Blood Pressure.International journal of molecular sciences · 2021Article
- Blockade of Human α7 Nicotinic Acetylcholine Receptor by α-Conotoxin ImI Dendrimer: Insight from Computational Simulations.Marine drugs · 2019Article
- Article
- Cholinergic modulation by opioid receptor ligands: potential application to Alzheimer's disease.Mini reviews in medicinal chemistry · 2013Review
- Blockade of neuronal α7-nAChR by α-conotoxin ImI explained by computational scanning and energy calculations.PLoS computational biology · 2011Article
- Gating of nicotinic ACh receptors: latest insights into ligand binding and function.The Journal of physiology · 2010Review
- Computational modeling study of human nicotinic acetylcholine receptor for developing new drugs in the treatment of alcoholism.Interdisciplinary sciences, computational life sciences · 2009Article
- Nicotinic receptors: allosteric transitions and therapeutic targets in the nervous system.Nature reviews. Drug discovery · 2009Review
- Number and locations of agonist binding sites required to activate homomeric Cys-loop receptors.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2009Article
- Effect of novel negative allosteric modulators of neuronal nicotinic receptors on cells expressing native and recombinant nicotinic receptors: implications for drug discovery.The Journal of pharmacology and experimental therapeutics · 2009Article
- The conformation of acetylcholine at its target site in the membrane-embedded nicotinic acetylcholine receptor.Proceedings of the National Academy of Sciences of the United States of America · 2007Article
- Galanthamine and non-competitive inhibitor binding to ACh-binding protein: evidence for a binding site on non-alpha-subunit interfaces of heteromeric neuronal nicotinic receptors.Journal of molecular biology · 2007Article
- Determinants of alpha-conotoxin BuIA selectivity on the nicotinic acetylcholine receptor beta subunit.Biochemistry · 2006Article
- Acetylcholine nicotinic receptors: finding the putative binding site of allosteric modulators using the "blind docking" approach.Journal of molecular modeling · 2006Article
- The characterization of a novel rigid nicotine analog with alpha7-selective nAChR agonist activity and modulation of agonist properties by boron inclusion.Bioorganic & medicinal chemistry letters · 2005Article
- Selective blockade of nicotinic acetylcholine receptors by pimobendan, a drug for the treatment of heart failure: reduction of catecholamine secretion and synthesis in adrenal medullary cells.Naunyn-Schmiedeberg's archives of pharmacology · 2005Article
- Subunit rotation models activation of serotonin 5-HT3AB receptors by agonists.Journal of computer-aided molecular design · 2004Article
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
(alpha3)2(beta4)3 is the most abundant type of neuronal nicotinic ACh receptor (nAChR) mediating cholinergic actions on the autonomic nervous system. Studies to refine or devise drugs selectively acting on (alpha3)2(beta4)3 receptors would benefit from a detailed description of the hitherto unclear agonist-binding domain. The present study reports a three-dimensional model for the ligand-binding domain (LBD) of this receptor either in its unoccupied or agonist-bound conformation. The receptor model was based on the structure of the acetylcholine-binding protein (AChBP), and was obtained using molecular modelling techniques. ACh, nicotine and cytisine (full agonists), muscarine (a selective agonist of muscarinic ACh receptors) and the allosteric modulator eserine were docked into the binding pockets of the receptor model. Simulated agonist-receptor complexes were compared with the agonist-binding complex of the AChBP, as well as of the (alpha4)2(beta2)3 type of nAChR, which is the commonest in the brain. Agonist docking identified discrete amino-acid residues of the beta subunits important for pharmacological selectivity of nAChRs. The predicted affinity of muscarine for the nAChR was low, suggesting the present model to be suitable for effective discrimination of nicotinic agonist binding versus nonselective cholinergic binding. Furthermore, the current model outlined a potential binding site for the allosteric modulator eserine, the site of action of which has remained elusive. The present LBD model of the receptor in its free state provides a novel structural framework to interpret experimental observations and a useful template for future investigations to develop (alpha3)2(beta4)3-selective ligands.
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