Proteolytic enzymes. Nature of binding forces between papain and its substrates and inhibitors

Abstract

The binding of papain to its substrate R¹CO·NH·CHR²·COX involves interaction between R¹CONH–, R²–, and –COX moieties and complementary sites (ρ₁, ρ₂ and ρ₃) on the enzyme. The ρ₁ and ρ₃ interactions involve lipophilic forces which are not of the charge-transfer type. The ρ₂ interaction is shown unequivocally not to involve electrostatic forces but depends on the length of the side-chain. Knowledge of the existence of the ρ₁ and ρ₃ binding sites has been used to design non-peptide reversible inhibitors of the enzyme.