Protein autoproteolysis: conformational strain linked to the rate of peptide cleavage by the pH dependence of the N -> O acyl shift reaction

The studies have shown that the pH dependence of autoproteolysis in a slow-cleaving mutant (1G) of the MUC1 SEA domain is consistent with the mechanism in which N -> O acyl shift has proceeded after initial protonation of the amide nitrogen. A mechanism involving strain, nitrogen protonation and N -> O shift is supported by the quantum chemical calculations.