The different mechanisms of protease action have a basic feature in common: proton transfer from the attacking nucleophile to the substrate leaving group.

The catalytic machineries of serine, cysteine, aspartic and zinc proteases are considerably different. It is pointed out in the light of most recent results that, in spite of the differences, the basic catalytic features of the four types of proteases is common. They all possess a proton carrier (imidazole, carboxylate ion or carboxylcarboxylate diad) which conveys the proton from the attacking nucleophile to the leaving group of the substrate. This uniform strategy facilitates both the formation and the decomposition of the tetrahedral intermediate, and renders regeneration of the enzyme simple.