Author: Iorga, B.; Herlem, D.; Barre, E.; Guillou, C.
Description: Allosteric potentiation of acetylcholine nicotinic receptors is considered to be one of the most promising approaches for the treatment of Alzheimer’s disease. However, the exact localization of the allosteric binding site and the potentiation mechanism at the molecular level are presently unknown. We have performed the “blind docking” of three known allosteric modulators (galanthamine, codeine and eserine) with the Acetylcholine Binding Protein and models of human alpha7, alpha3beta4 and alpha4beta2 nicotinic receptors, created by homology modeling. Three putative binding sites were identified in the channel pore, each one showing different affinities for the ligands. One of these sites is localized opposite to the agonist binding site and is probably implicated in the potentiation process. On the basis of these results, a possible mechanism for nicotinic acetylcholine receptor (nAChRs) activation is proposed. The present findings may represent an important advance for understanding the allosteric modulation mechanism of nAChRs. [Figure: see text].
Subject headings: Allosteric Site; Amino Acid Sequence; Conserved Sequence; Humans; Models, Molecular; Molecular Sequence Data; Protein Structure, Quaternary; Protein Subunits/chemistry/metabolism; Receptors, Nicotinic/chemistry/metabolism; Sequence Alignment
Publication year: 2006
Journal or book title: Journal of Molecular Modeling
Volume: 12
Issue: 3
Pages: 366-372
Find the full text : https://link.springer.com/article/10.1007/s00894-005-0057-z
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Type: Journal Article
Serial number: 1889