The structure of chagasin in complex with a cysteine protease clarifies the binding mode and evolution of an inhibitor family

Structure. 2007 May;15(5):535-43. doi: 10.1016/j.str.2007.03.012.


Protein inhibitors of proteolytic enzymes regulate proteolysis and prevent the pathological effects of excess endogenous or exogenous proteases. Cysteine proteases are a large family of enzymes found throughout the plant and animal kingdoms. Disturbance of the equilibrium between cysteine proteases and natural inhibitors is a key event in the pathogenesis of cancer, rheumatoid arthritis, osteoporosis, and emphysema. A family (I42) of cysteine protease inhibitors ( was discovered in protozoan parasites and recently found widely distributed in prokaryotes and eukaryotes. We report the 2.2 A crystal structure of the signature member of the I42 family, chagasin, in complex with a cysteine protease. Chagasin has a unique variant of the immunoglobulin fold with homology to human CD8alpha. Interactions of chagasin with a target protease are reminiscent of the cystatin family inhibitors. Protein inhibitors of cysteine proteases may have evolved more than once on nonhomologous scaffolds.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cysteine Endopeptidases / chemistry*
  • Cysteine Endopeptidases / physiology
  • Evolution, Molecular*
  • Molecular Sequence Data
  • Multigene Family*
  • Protease Inhibitors*
  • Protein Binding / physiology
  • Protozoan Proteins / chemistry*
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism
  • Trypanosoma cruzi / chemistry
  • Trypanosoma cruzi / genetics
  • Trypanosoma cruzi / metabolism


  • Protease Inhibitors
  • Protozoan Proteins
  • chagasin, Trypanosoma
  • Cysteine Endopeptidases

Associated data

  • PDB/2OUL