X-Ray Crystallographic Studies on Acetylcholinesterase and on its Interactionwith Anticholinesterase Agents

摘要

The objective of this project was to solve, for the first time, by X-raycrystallography, the three-dimensional structure of acetylcholinesterase (AChE) and to learn from this structure the reaction mechanism, inhibition modes and other structural and functional properties of the enzyme. The principal objectives of the current project included: (1) Attempts to obtain crystals of cholinesterases other than T. californica AChE, in particular of AChE of human origin. (2) Collection of improved data sets, viz. at higher resolution than previously, for crystals of Torpedo AChE. (3) Determination of complexes of Torpedo AChE with various ligands, including orgamophosphates. In the this project, we have made progress towards all three objectives, as well as in additional areas related to the long-term aims of our research program.