Affordable Access

Multiple allosteric sites on muscarinic receptors.

Authors
  • Birdsall, N J
  • Lazareno, S
  • Popham, A
  • Saldanha, J
Type
Published Article
Journal
Life Sciences
Publisher
Elsevier
Publication Date
Apr 27, 2001
Volume
68
Issue
22-23
Pages
2517–2524
Identifiers
PMID: 11392621
Source
Medline
License
Unknown

Abstract

Proteins and small molecules are capable of regulating the agonist binding and function of G-protein coupled receptors by multiple allosteric mechanisms. In the case of muscarinic receptors, there is the well-characterised allosteric site that binds, for example, gallamine and brucine. The protein kinase inhibitor, KT5720, has now been shown to bind to a second allosteric site and to regulate agonist and antagonist binding. The binding of brucine and gallamine does not affect KT5720 binding nor its effects on the dissociation of [3H]-N-methylscopolamine from M1 receptors. Therefore it is possible to have a muscarinic receptor with three small ligands bound simultaneously. A model of the M1 receptor, based on the recently determined structure of rhodopsin, has the residues that have been shown to be important for gallamine binding clustered within and to one side of a cleft in the extracellular face of the receptor. This cleft may represent the access route of acetylcholine to its binding site.

Report this publication

Statistics

Seen <100 times