Ligand binding: proteinase protein inhibitor interactions

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