2OUL: The Structure of Chagasin in Complex With a Cysteine Protease Clarifies the Binding Mode and Evolution of a NEW Inhibitor Family

Citation:
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 (http://merops.sanger.ac.uk) 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.
PDB ID: 2OULDownload
MMDB ID: 62654
PDB Deposition Date: 2007/2/11
Updated in MMDB: 2012/11 
Experimental Method:
x-ray diffraction
Resolution: 2.2  Å
Source Organism:
Plasmodium falciparum 3D7
Similar Structures:
Biological Unit for 2OUL: dimeric; determined by author
Molecular Components in 2OUL
Label Count Molecule
Proteins (2 molecules)
1
Falcipain 2
Molecule annotation
1
Chagasin
Molecule annotation
* Click molecule labels to explore molecular sequence information.

Citing MMDB
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