The basic difference in catalyses by serine and cysteine proteinases resides in charge stabilization in the transition state.

Besides the mechanistic similarities, in particular acylenzyme formation, kinetic investigations and X-ray diffraction studies have revealed some differences between the mechanisms of serine and cysteine proteinases: general base-catalysis in acylation, catalytic contribution by oxyanion binding, and a negatively charged catalytic triad in serine proteinases, but not in cysteine proteinases. In this paper we point out that all these differences are related and connected with the mode of stabilization of the zwitterionic species developing in the transition state of the reactions. In the case of serine proteinases this charge separation requires facilitation by the oxyanion binding and the negative charge of the catalytic triad. On the other hand cysteine proteinases do not require such contributions as they are capable of stabilizing the ion-pair even in the ground state of the reaction. Therefore, cysteine proteinases, in contrast to serine proteinases, may be regarded as "activated" enzymes.