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Identification of multiple allosteric sites on the M 1 muscarinic acetylcholine receptor
Author(s) -
Espinoza-Fonseca L. Michel,
Trujillo-Ferrara José G.
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2005.10.069
Subject(s) - allosteric regulation , muscarinic acetylcholine receptor , muscarinic acetylcholine receptor m5 , muscarinic acetylcholine receptor m2 , muscarinic acetylcholine receptor m3 , muscarinic acetylcholine receptor m1 , chemistry , acetylcholine receptor , identification (biology) , muscarinic acetylcholine receptor m4 , acetylcholine , receptor , biochemistry , pharmacology , biology , ecology
Staurosporine and four staurosporine derivatives were docked on the rhodopsin‐based homology model of the M 1 muscarinic acetylcholine receptor in order to localize the possible allosteric sites of this receptor. It was found that there were three major allosteric sites, two of which are located at the extracellular face of the receptor, and one in the intracellular domain of the receptor. In the present study, the localization of these binding sites is described for the first time. The present study confirms the existence of multiple allosteric sites on the M 1 muscarinic receptor, and lays the ground for further experimental and computational analysis to better understand how muscarinic receptors are modulated via their allosteric sites. These findings will also help to design and develop novel drugs acting as allosteric modulators of the M 1 receptor, which can be used in the treatment of the Alzheimer's disease.