Natural protein proteinase inhibitors and their interaction with proteinases

Authors

  • Wolfram BODE,

    Corresponding author
    1. Max-Planck-Institut für Biochemie, Martinsried, Federal Republic of Germany
      Correspondence to W. Bode, Max-Planck-Institut für Biochemie, W-8033 Martinsried; Federal Republic of Germany
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  • Robert HUBER

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

Abstract

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.

Abbreviations
 

P1, P2, P3 etc. and P1′, P2′, P3′ etc., designate substrate/inhibitor residues amino-terminal and carboxy-terminal of the scissile peptide bond, respectively, and S1, S2, S3 etc. and S1′, S2′, S3′ etc., the corresponding subsites of the cognate proteinases [1]. Abbreviations of the inhibitors are explained in Table 1

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