The enzyme should be looked at straight down the deep gorge that leads to the active binding site for the acetylcholine substrate. In the deepest region of the gorge can be found the catalytic triad, of which the serine hydroxyl is 4A above the base of the gorge. This is the location where the main catalytic activity occurs in the AChE molecule. In the first step. The hydroxyl group on serine 200 nucleophilically attacks the carbonyl carbon of the choline, and forms a tetrahedral intermediate. This intermediate is further stabilized by the imidazole nitrogen on the histidine (His440). During the second step, the ester oxygen leaves the tetrahedral intermediate and forms another ester with the serine. The histidine is then deprotonated by an oxygen on the choline molecule. During the third step, histidine (His440) deprotonates a water molecule, therefore making it more nuclephilic. This molecule can then attack the carbonyl carbon of the choline again forming the tetrahedral intermediate. During the fourth step, the intermediate collapses to form acetate. The serine oxygen then receives a proton from the imidazole nitrogen. Therefore, the enzyme is regenerated through a number of other nucleophilic reactions.
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View of Catalytic Triad
The catalytic triad of amino acids are Ser200, His440, and Glu327. As a point of reference, the residues Tyr70 and Trp279 are shown because they mark the peripheral site of the gorge.
Different View of Catalytic Triad
The model of AChE is shown without the surrounding structures, and only with the catalytic triad and the peripheral marker discussed in the previous figure. The white markers present represent the hydrogen bonds within the AChE itself. It is shown as a backbone for reference.