Rational Understanding of Nicotinic Receptors Drug Binding

Author(s): Thomas Grutter, Nicolas Le Novere, Jean-Pierre Changeux

Journal Name: Current Topics in Medicinal Chemistry

Volume 4 , Issue 6 , 2004


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Abstract:

The atomic determination of the acetylcholine binding protein (AChBP), a molluscan cholinergic protein, homologous to the amino-terminal extracellular domain of nicotinic receptors (nAChRs), offers opportunities for the modeling of the acetylcholine binding site and its ligands. Recently, we constructed three-dimensional models of the Nterminal part of nAChR and docked in the putative ligand-binding pocket, different agonists (acetylcholine, nicotine and epibatidine) and antagonist (snake α-bungarotoxin). These hypothetical docking models offer a structural basis for rational design of drugs differentially binding to resting and active (or desensitized) conformations of the receptor site. These models thus pave the way to investigate, at the molecular level, the exciting challenge of the fast ion channel gating mechanisms by nicotinic agonists.

Keywords: nicotinic acetylcholine receptor, structure activity relationship, allosteric transitions, drug design

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Article Details

VOLUME: 4
ISSUE: 6
Year: 2004
Page: [645 - 651]
Pages: 7
DOI: 10.2174/1568026043451177
Price: $65

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