Acetylcholinesterase (AChE) is found predominantly in the brain, striated muscle and blood, which is an enzyme that breaks down acetylcholine (ACh). It is a therapeutic target to control neurodegenerative diseases such as Alzheimer disease. Donepezil is a reversible, selective AChE inhibitor that is currently approved for the symptomatic treatment for AD. It inhibits the breakdown of AChE and compensate the deficiency of AChE in the brain. In this model, we highlight the key structure of AChE which are crucial for hydrolysis of ACh, as well as two newly discoverd allosteric druggable sites, site 2 and site 3. Structure of donepezil and its interaction with AChE are also included to demonstrate how the catalytic activity of AChE can be inhibited by an inhibitor.
References https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010107/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4395452/
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