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Structural Basis of Agonist Selectivity for Different nAChR Subtypes: Insights from Crystal Structures, Mutation Experiments and Molecular Simulations
- Source :
- Current Pharmaceutical Design. 17:1652-1662
- Publication Year :
- 2011
- Publisher :
- Bentham Science Publishers Ltd., 2011.
-
Abstract
- Nicotinic acetylcholine receptors (nAChRs) are members of ligand gated ion channels (LGICs) which transduce chemical signal into electrical signal in neuron and neuromuscular junction. They are pentamerics which contain an extra-cellular domain (also known as ligand binding domain or LBD), a trans-membrane domain and a cytoplasmic domain (intra-cellular domain). Agonist binding to the extra-cellular domain invokes positive ion flux as well as action potential in neurons, muscle cells and endocrine cells whereas antagonist binding inhibits ion flux. There are various endogenous or exogenous compounds which behave as agonists or antagonists targeting nAChRs. During the last decades, the whole structure of muscle type nAChR as well as the crystal structures of acetylcholine-binding proteins (AChBPs) which are homologues of the nAChRs extra-cellular domain has been obtained. These structures, together with other studies including mutation experiments and molecular simulations, provide insights into both of the nAChR architecture and its agonist binding cavity. Our review gives detailed accounts of the recent progresses in order to gain insights into agonist selectivity for different nAChR subtypes.
- Subjects :
- Models, Molecular
Pharmacology
Agonist
Mutation
Protein Conformation
medicine.drug_class
Chemistry
Nicotinic Antagonists
Crystallography, X-Ray
medicine.disease_cause
Neuromuscular junction
Nicotinic agonist
medicine.anatomical_structure
nervous system
Biochemistry
Drug Discovery
medicine
Biophysics
Ligand-gated ion channel
Myocyte
Neuron
Acetylcholine receptor
Subjects
Details
- ISSN :
- 13816128
- Volume :
- 17
- Database :
- OpenAIRE
- Journal :
- Current Pharmaceutical Design
- Accession number :
- edsair.doi.dedup.....3bd63dfd4ff7e1e4c9deac70fc4c392f