Cellular and Molecular Life Sciences CMLS

, Volume 60, Issue 11, pp 2427–2444

Canonical protein inhibitors of serine proteases

Review

DOI: 10.1007/s00018-003-3120-x

Cite this article as:
Krowarsch, D., Cierpicki, T., Jelen, F. et al. CMLS, Cell. Mol. Life Sci. (2003) 60: 2427. doi:10.1007/s00018-003-3120-x

Abstract

Serine proteases and their natural protein inhibitors are among the most intensively studied protein complexes. About 20 structurally diverse inhibitor families have been identified, comprising α-helical, β sheet, and α/β proteins, and different folds of small disulfide-rich proteins. Three different types of inhibitors can be distinguished based on their mechanism of action: canonical (standard mechanism) and non-canonical inhibitors, and serpins. The canonical inhibitors bind to the enzyme through an exposed convex binding loop, which is complementary to the active site of the enzyme. The mechanism of inhibition in this group is always very similar and resembles that of an ideal substrate. The non-canonical inhibitors interact through their N-terminal segment. There are also extensive secondary interactions outside the active site, contributing significantly to the strength, speed, and specificity of recognition. Serpins, similarly to the canonical inhibitors, interact with their target proteases in a substrate-like manner; however, cleavage of a single peptide bond in the binding loop leads to dramatic structural changes.

Serine proteaseprotein inhibitorcanonical conformationprotein-protein recognition

Copyright information

© Birkhäuser-Verlag Basel 2003

Authors and Affiliations

  • D. Krowarsch
    • 1
  • T. Cierpicki
    • 1
  • F. Jelen
    • 1
  • J. Otlewski
    • 1
  1. 1.Institute of Biochemistry and Molecular BiologyUniversity of WroclawWroclaw