Visualization of Acetylcholinesterase: Nature's Vacuum Cleaner
Acetylcholinesterase (AcChoEase) is an enzyme that plays a key role in the
human nervous system. In vertebrates, nerve impulses travel from cell to
cell by means of chemical messenger. When an electrical impulse reaches the
end of one cell, messenger molecules--acetylcholine (AcCho), in this
case--are released to diffuse though the fluid-filled, intercellular,
synaptic gap. Upon reaching the destination cell, the AcCho molecules dock
into special receptors triggering a new electrical impulse. Much like a
vacuum cleaner, the enzyme AcChoEase is constantly sweeping up and
hydrolyzing AcCho during this process, so that the whole cycle can begin
again.
Chemicals that inhibit the action of AcChoEase are being used in the
treatment of glaucoma, myasthenia gravis and, experimentally, Alzheimer's
disease. In spite of the ability to exploit the enzyme, its precise
mechanism of operation is still a mystery.
The recent solution of the X-ray structure for AcChoEase, places the active
catalytic site deep within a gorge-like fold of the protein. Electrostatic
computations reveal the enzyme to be a single massive dipole. Such a
configuration of charge suggests an electrostatic mechanism for directing
the positively charged AcCho into the gorge and towards the active site.
Collaborators
Cornell University, USA
Weizmann Institute of Science, Israel
Contact
Richard Gillilan
Cornell University, USA
richard@tc.cornell.edu
Contact
Joel L. Sussman
Weizmann Institute of Science, Israel
Joel.Sussman@weizmann.ac.il
Israel Silman
Weizmann Institute of Science, Israel
Israel.Silman@weizmann.ac.il