2oul
From Proteopedia
The Structure of Chagasin in Complex with a Cysteine Protease Clarifies the Binding Mode and Evolution of a New Inhibitor Family
Overview
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.
About this Structure
2OUL is a Protein complex structure of sequences from Plasmodium falciparum and Trypanosoma cruzi. Full crystallographic information is available from OCA.
Reference
The structure of chagasin in complex with a cysteine protease clarifies the binding mode and evolution of an inhibitor family., Wang SX, Pandey KC, Scharfstein J, Whisstock J, Huang RK, Jacobelli J, Fletterick RJ, Rosenthal PJ, Abrahamson M, Brinen LS, Rossi A, Sali A, McKerrow JH, Structure. 2007 May;15(5):535-43. PMID:17502099 Page seeded by OCA on Sun May 4 11:41:16 2008
