The Human Protease Inhibitor Cystatin C Is an Activating Cofactor for the Streptococcal Cysteine Protease IdeS.
(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:
https://lup.lub.lu.se/record/1242875
- author
- Vincents, Bjarne LU ; Vindebro, Reine ; Abrahamson, Magnus LU and von Pawel-Rammingen, Ulrich
- organization
- publishing date
- 2008
- 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
- pmid:18804033
- 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
- 2016-04-04 08:14:54
- date last changed
- 2022-01-29 03:10:42
@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}},
doi = {{10.1016/j.chembiol.2008.07.021}},
volume = {{15}},
year = {{2008}},
}