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

Wang, Stephanie X.; Pandey, Kailash C.; Scharfstein, Julio; Whisstock, James; Huang, Rick K.; Jacobelli, Jordan; Fletterick, Robert J.; Rosenthal, Philip J.; Abrahamson, Magnus LU and Brinen, Linda S., et al. (2007) In Structure 15(5). p.535-543
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 (142) 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 142 family, chagasin, in complex with a cysteine protease. Chagasin has a... (More)
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 (142) 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 142 family, chagasin, in complex with a cysteine protease. Chagasin has a unique variant of the immunoglobulin fold with homology to human CD8 alpha. 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. (Less)
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Structure
volume
15
issue
5
pages
535 - 543
publisher
Cell Press
external identifiers
  • wos:000246605800005
  • scopus:34248154849
ISSN
0969-2126
DOI
10.1016/j.str.2007.03.012
language
English
LU publication?
yes
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bcae66d8-0edf-4b4b-8f7c-9c22297d2495 (old id 661044)
date added to LUP
2008-01-03 10:22:38
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2017-11-19 03:34:40
@article{bcae66d8-0edf-4b4b-8f7c-9c22297d2495,
  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 (142) 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 142 family, chagasin, in complex with a cysteine protease. Chagasin has a unique variant of the immunoglobulin fold with homology to human CD8 alpha. 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.},
  author       = {Wang, Stephanie X. and Pandey, Kailash C. and Scharfstein, Julio and Whisstock, James and Huang, Rick K. and Jacobelli, Jordan and Fletterick, Robert J. and Rosenthal, Philip J. and Abrahamson, Magnus and Brinen, Linda S. and Rossi, Andrea and Sali, Andrej and McKerrow, James H.},
  issn         = {0969-2126},
  language     = {eng},
  number       = {5},
  pages        = {535--543},
  publisher    = {Cell Press},
  series       = {Structure},
  title        = {The structure of chagasin in complex with a cysteine protease clarifies the binding mode and evolution of an inhibitor family},
  url          = {http://dx.doi.org/10.1016/j.str.2007.03.012},
  volume       = {15},
  year         = {2007},
}