title: Docking of alpha-cobratoxin suggests a basal conformation of the nicotinic receptor.
abstract: We investigate the interactions between the long chain alpha-cobratoxin (Cbtx) and the nicotinic acetylcholine receptor using a rigid body docking procedure. The method, (i) reproduces the binding of Cbtx to Lymnea acetylcholine-binding protein (AChBP); (ii) shows that most of the structures of AChBP obtained in the presence of antagonists are compatible with Cbtx binding; and (iii) reveals a complex between Cbtx and muscle nAChR that corresponds to the basal "resting" state conformation. The structures are made available for further understanding of the allosteric transitions of the nAChR as well as for drug design.
authors.affiliation: Recepteurs et Cognition, Unité de Recherche Associée, Centre National de la Recherche Scientifique 2182, Institut Pasteur, Paris, France.
authors.forename: Maria
authors.initials: M
authors.lastname: Konstantakaki
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Changeux
authors.forename: Antoine
authors.initials: A
authors.lastname: Taly
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism; D003039:Cobra Neurotoxin Proteins / Q000737:chemistry* / Q000378:metabolism*; D018360:Crystallography, X-Ray; D017815:Elapidae / Q000378:metabolism*; D008195:Lymnaea / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D009132:Muscles / Q000378:metabolism; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011485:Protein Binding; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D011978:Receptors, Nicotinic / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D002352:Carrier Proteins; D003039:Cobra Neurotoxin Proteins; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; C025154:alpha-cobratoxin