Conformational flexibility in the peripheral site of Torpedo californica acetylcholinesterase revealed by the complex structure with a bifunctional inhibitor.
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.
Colletier
Jacques Ph
JP
Laboratoire de Biophysique Moléculaire, Institut de Biologie Structurale, 38027 Grenoble, France.
Sanson
Benoît
B
Nachon
Florian
F
Gabellieri
Emanuele
E
Fattorusso
Caterina
C
Campiani
Giuseppe
G
Weik
Martin
M
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
D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase