2OUL

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

Summary for 2OUL

• Entry DOI: 10.2210/pdb2oul/pdb
• Related: 1YVB
• Descriptor: Falcipain 2, Chagasin (3 entities in total)
• Functional Keywords: cysteine protease, inhibitor, macromolecular interaction, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• Biological source: Plasmodium falciparum; More
• Total number of polymer chains: 2
• Total formula weight: 39241.15

Authors

Wang, S.X.,Chand, K.,Huang, R.,Whisstock, J.,Jacobelli, J.,Fletterick, R.J.,Rosenthal, P.J.,McKerrow, J.H. (deposition date: 2007-02-11, release date: 2008-02-26, Last modification date: 2024-10-16)

Primary citation

Wang, S.X.,Pandey, K.C.,Scharfstein, J.,Whisstock, J.,Huang, R.K.,Jacobelli, J.,Fletterick, R.J.,Rosenthal, P.J.,Abrahamson, M.,Brinen, L.S.,Rossi, A.,Sali, A.,McKerrow, J.H.
The structure of chagasin in complex with a cysteine protease clarifies the binding mode and evolution of an inhibitor family.
Structure, 15:535-543, 2007

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 (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.

PubMed: 17502099
DOI: 10.1016/j.str.2007.03.012

Experimental method

X-RAY DIFFRACTION (2.2 Å)