Abstract
The general features of acetylcholinesterase (AChE*) catalysis outlined in Figure 1 have been appreciated for some time (Froede and Wilson, 1971; Quinn, 1987; Rosenberry, 1975). The first step, nucleophilic attack by S200, is assisted by general-base catalysis by H440 and produces a tetrahedral intermediate, which collapses to the acylenzyme by general-acid catalyzed expulsion of choline by H440. The deacylation stage of catalysis follows a similar series of events, with eventual expulsion from the tetrahedral intermediate of S200 of the active site. Figure 1 also raises the possibility that E327 functions with H440 in a proton relay network, an example of charge-relay catalysis (Blow, 1976).
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References
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Quinn, D.M. et al. (1992). Cryptic Catalysis and Cholinesterase Function. In: Shafferman, A., Velan, B. (eds) Multidisciplinary Approaches to Cholinesterase Functions. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3046-6_19
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