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Acetylcholine hydrolysis by acetylcholinesterase is inhi-bited at high substrate concentrations. To determine theresidues involved in this phenomenon, we have mutatedmost of the residues lining the active-site gorge butmutating these did not completely eliminate hydrolysis.Thus, we analyzed the effect of a nonhydrolysable sub-strate analogue on substrate hydrolysis and on reactiva-tion of an analogue of the acetylenzyme. Analyses ofvarious models led us to propose the following sequenceof events:the substrate initially binds at the rim of theactive-site gorge and then slides down to the bottom ofthe gorge where it is hydrolyzed....
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Báo cáo khoa học: Inhibition of Drosophila melanogaster acetylcholinesterase by high concentrations of substrate
