Proteinase-protein inhibitor interaction

Until recently, the "substrate-like" "canonical" inhibition by the "small" serine proteinase inhibitors, and the product-like inhibition by the carboxypeptidase inhibitor, provided the only models for protein inhibitor-proteinase interactions. The recently published structures of cystatin/stefin-papain complexes and of hirudin-thrombin complexes reveal novel modes of interactions of only partial substrate-like character. Despite considerable progress in understanding the native-cleaved transition of the serpins, the mechanisms of their interaction with their cognate serine proteinases is still a matter of conjecture.