Identification of multiple allosteric sites on the M1 muscarinic acetylcholine receptor

L. Michel Espinoza-Fonseca, José G. Trujillo-Ferrara

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Staurosporine and four staurosporine derivatives were docked on the rhodopsin-based homology model of the M1 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 M1 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 M1 receptor, which can be used in the treatment of the Alzheimer's disease.

Original languageEnglish (US)
Pages (from-to)6726-6732
Number of pages7
JournalFEBS Letters
Volume579
Issue number30
DOIs
StatePublished - Dec 19 2005

Keywords

  • Allosteric sites
  • Alzheimer's disease
  • Docking simulations
  • G-protein coupling receptors
  • M muscarinic acetylcholine receptor
  • Molecular dynamics
  • staurosporine

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