[Exploring the conformational energy landscape of acetylcholinesterase by kinetic crystallography].
Acetylcholinesterase is a very rapid enzyme, essential in the process of nerve impulse transmission at cholinergic synapses. It is the target of all currently approved anti-Alzheimer drugs and further progress in the modulation of its activity requires structural as well as dynamical information. Exploration of the conformational energy landscape of a protein by means of X-ray crystallography requires the use of experimental tricks, to overcome the inherently static nature of crystallographic structures. Here we report three experimental approaches that allowed to gain structural insight into the dynamics of acetylcholinesterase, which is relevant for structure-based drug design.
Colletier
J-P
JP
CEA-CNRS-UJF, Institut de biologie structurale J.-P. Ebel, Umr 5075, Laboratoire de biophysique moléculaire, F 38027 Grenoble. jpcolletier@hotmail.com
Weik
M
M
D000110:Acetylcholinesterase / Q000737:chemistry*; D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D002794:Choline / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D018360:Crystallography, X-Ray; D015195:Drug Design; D004735:Energy Transfer; D006801:Humans; D007700:Kinetics; D011487:Protein Conformation
D002800:Cholinesterase Inhibitors; D000110:Acetylcholinesterase; D002794:Choline