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The Human Protease Inhibitor Cystatin C Is an Activating Cofactor for the Streptococcal Cysteine Protease IdeS.

Vincents, Bjarne LU ; Vindebro, Reine; Abrahamson, Magnus LU and von Pawel-Rammingen, Ulrich (2008) In Chemistry and Biology 15(9). p.960-968
Abstract
Human cystatin C is considered the physiologically most important inhibitor of endogenous papain-like cysteine proteases. We present here an unexpected function of cystatin C. Instead of acting as an inhibitor, cystatin C acts as a facultative, endogenous cofactor for the papain-like IgG-cleaving enzyme IdeS of the human pathogen Streptococcus pyogenes. IdeS activity is not dependent on cystatin C, but is significantly enhanced in the presence of cystatin C. We report a protease inhibitor that accelerates the activity of its putative target protease and a unique example of how a host protease inhibitor is "hijacked" by a bacterial protease to increase its activity. This finding has important implications for the view on protease-inhibitor... (More)
Human cystatin C is considered the physiologically most important inhibitor of endogenous papain-like cysteine proteases. We present here an unexpected function of cystatin C. Instead of acting as an inhibitor, cystatin C acts as a facultative, endogenous cofactor for the papain-like IgG-cleaving enzyme IdeS of the human pathogen Streptococcus pyogenes. IdeS activity is not dependent on cystatin C, but is significantly enhanced in the presence of cystatin C. We report a protease inhibitor that accelerates the activity of its putative target protease and a unique example of how a host protease inhibitor is "hijacked" by a bacterial protease to increase its activity. This finding has important implications for the view on protease-inhibitor interactions, and is relevant to consider in the therapeutic use of protease inhibitors. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Chemistry and Biology
volume
15
issue
9
pages
960 - 968
publisher
Cell Press
external identifiers
  • wos:000259918200011
  • pmid:18804033
  • scopus:51649097889
ISSN
1879-1301
DOI
10.1016/j.chembiol.2008.07.021
language
English
LU publication?
yes
id
8e2a9483-859b-4f11-9cec-5bb94112675c (old id 1242875)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/18804033?dopt=Abstract
date added to LUP
2008-10-03 17:07:03
date last changed
2017-01-01 07:35:44
@article{8e2a9483-859b-4f11-9cec-5bb94112675c,
  abstract     = {Human cystatin C is considered the physiologically most important inhibitor of endogenous papain-like cysteine proteases. We present here an unexpected function of cystatin C. Instead of acting as an inhibitor, cystatin C acts as a facultative, endogenous cofactor for the papain-like IgG-cleaving enzyme IdeS of the human pathogen Streptococcus pyogenes. IdeS activity is not dependent on cystatin C, but is significantly enhanced in the presence of cystatin C. We report a protease inhibitor that accelerates the activity of its putative target protease and a unique example of how a host protease inhibitor is "hijacked" by a bacterial protease to increase its activity. This finding has important implications for the view on protease-inhibitor interactions, and is relevant to consider in the therapeutic use of protease inhibitors.},
  author       = {Vincents, Bjarne and Vindebro, Reine and Abrahamson, Magnus and von Pawel-Rammingen, Ulrich},
  issn         = {1879-1301},
  language     = {eng},
  number       = {9},
  pages        = {960--968},
  publisher    = {Cell Press},
  series       = {Chemistry and Biology},
  title        = {The Human Protease Inhibitor Cystatin C Is an Activating Cofactor for the Streptococcal Cysteine Protease IdeS.},
  url          = {http://dx.doi.org/10.1016/j.chembiol.2008.07.021},
  volume       = {15},
  year         = {2008},
}