“…By analogy to nonenzymatic acyl-transfer reactions, tetrahedral structures are presumed to be intermediates in normal peptide hydrolyses catalyzed by serine proteinases, but have never been directly observed, and are presumed to exist only in low steady-state amounts. They are extremely unstable, approaching the transition-state energy for enzyme acylation, typically [16][17][18][19] keal/mol less stable than the concovalent Michaelis-Menten-type complexes from which they are derived.57'58 Such species, to exist in detectable amounts, would require specific and highly effective stabilization. Rather than accounting for the stability of these enzyme-inhibitor complexes, the existence of such a structure would more likely decrease their stability.…”