The Structure of Chagasin in Complex with a Cysteine Protease Clarifies the Binding Mode and Evolution of an Inhibitor Family

Department of Pathology, University of California, San Francisco, San Francisco, CA 94143, USA.
Structure (Impact Factor: 6.79). 06/2007; 15(5):535-43. DOI: 10.1016/j.str.2007.03.012
Source: PubMed

ABSTRACT 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.


Available from: Kailash Pandey, Jun 03, 2015
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