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.
Original language | English |
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Pages (from-to) | 960-968 |
Journal | Chemistry and Biology |
Volume | 15 |
Issue number | 9 |
DOIs | |
Publication status | Published - 2008 |
Subject classification (UKÄ)
- Medicinal Chemistry
- Pharmacology and Toxicology