Substrate-ligand interactions with acetylcholinesterase and energetics of binding

Ester hydrolysis by acetylcholinesterase (from electric eel, Electrophorus electricus) increased in the presence of low concentrations (ca 10(-7) M) of edrophonium, propidium, d-tubocurarine, gallamine, decamethonium or bis-N-methylacridinium, and decreased at higher concentrations. The overall sensitivity of the substrates to inhibition by the ligands was acetylcholine (Ach) greater than phenylacetate (PA) greater than indophenylacetate (IPA). Complete (saturable) inhibition was unattainable with edrophonium or gallamine for IPA and, to a lesser degree, with propidium for PA. Reaction heats between the enzyme and the ligands (edrophonium, propidium and decamethonium) measured directly in a microcalorimeter revealed binding sites that are different from each other in their interaction energetics.