Shape-shifting serpins--advantages of a mobile mechanism

Trends Biochem Sci. 2006 Aug;31(8):427-35. doi: 10.1016/j.tibs.2006.06.005. Epub 2006 Jul 3.

Abstract

Serpins use an extraordinary mechanism of protease inhibition that depends on a rapid and marked conformational change and causes destruction of the covalently linked protease. Serpins thus provide stoichiometric, irreversible inhibition, and their dependence on conformational change is exploited for signalling and clearance. The regulatory advantages provided by structural mobility are best illustrated by the heparin activation mechanisms of the plasma serpins antithrombin and heparin cofactor II. This mechanistic complexity, however, renders serpins highly susceptible to disease-causing mutations. Recent crystal structures reveal the intricate conformational rearrangements involved in protease inhibition, activity modulation and the unique molecular pathology of the remarkable shape-shifting serpins.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antithrombins / chemistry
  • Antithrombins / physiology
  • Heparin Cofactor II / chemistry
  • Heparin Cofactor II / physiology
  • Humans
  • Kinetics
  • Models, Molecular
  • Protein Conformation*
  • Serine Endopeptidases / chemistry
  • Serine Endopeptidases / metabolism
  • Serpins / chemistry*
  • Serpins / physiology

Substances

  • Antithrombins
  • Serpins
  • Heparin Cofactor II
  • Serine Endopeptidases