title: Conformational flexibility in the peripheral site of Torpedo californica acetylcholinesterase revealed by the complex structure with a bifunctional inhibitor.
abstract: The X-ray crystallographic structure of Torpedo californica acetylcholinesterase (TcAChE) in complex with the bifunctional inhibitor NF595, a potentially new anti-Alzheimer drug, has been solved. For the first time in TcAChE, a major conformational change in the peripheral-site tryptophan residue is observed upon complexation. The observed conformational flexibility highlights the dynamic nature of protein structures and is of importance for structure-based drug design.
authors.affiliation: Laboratoire de Biophysique Moléculaire, Institut de Biologie Structurale, 38027 Grenoble, France.
authors.forename: Jacques Ph
authors.initials: JP
authors.lastname: Colletier
authors.forename: Benoît
authors.initials: B
authors.lastname: Sanson
authors.forename: Florian
authors.initials: F
authors.lastname: Nachon
authors.forename: Emanuele
authors.initials: E
authors.lastname: Gabellieri
authors.forename: Caterina
authors.initials: C
authors.lastname: Fattorusso
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Campiani
authors.forename: Martin
authors.initials: M
authors.lastname: Weik
mesh_terms: D000110:Acetylcholinesterase / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000737:chemistry*; D018360:Crystallography, X-Ray; D006801:Humans; D008958:Models, Molecular; D011487:Protein Conformation; D013816:Thermodynamics; D014101:Torpedo / Q000378:metabolism
chemical_list: D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase