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Similar to Endo IV, the pro-Rp rather than the pro-Sp nonbridging oxygen of the scissile phosphate is intolerant of thio-replacement.
Two conserved His residues surrounding the scissile phosphate haven shown to be important for the general acid-and-base catalysis, and the His mutations can be rescued by imidazole.
In the proposed mechanism for sedolisin, Glu80 acts as a general base to accept a proton from Ser287 during the nucleophilic attack and then as a general acid to protonate the leaving group during the cleavage of the scissile bond.