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. 2023 Apr 5;66(8):5364–5376. doi: 10.1021/acs.jmedchem.3c00097

Figure 6.

Figure 6

Schematic representation of the assisted-water mechanism proposed by Yu et al.45 Step 1: His48, which acts as a general base catalyst, abstracts a proton from the second water, which deprotonates the calcium-bound water molecule. This leads to the nucleophilic attack by the calcium-bound water on the carbonyl carbon of the substrate and the formation of the tetrahedral intermediate. Step 2: The departing alcoholate leaving group is protonated by the second water, which is itself protonated by His 48. Step 3: Collapses and the products are released.