Natural protein proteinase inhibitors and their interaction with proteinases


Correspondence to W. Bode, Max-Planck-Institut für Biochemie, W-8033 Martinsried; Federal Republic of Germany


The substrate-like ‘canonical' inhibition by the ‘small’ serine proteinase inhibitors and the product-like inhibition by the carboxypeptidase inhibitor have provided the only atomic models of protein inhibitor–proteinase interactions for about 15 years. The recently published structures of cystatin/stefin – papain complexes and of hirudin – thrombin complexes reveal novel non-substrate - like interactions. In addition, the structure of pro-carboxypeptidase showes a mode of inactivation which bears resemblance to proteinase/protein inhibitor systems. Considerable progress in understanding the transition between native and cleaved states of the serpins has also been made by several recent structural studies.