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

Summary, in English

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.

• Författare: Bjarne Vincents; Reine Vindebro; Magnus Abrahamson; Ulrich von Pawel-Rammingen
• Avdelning/ar: Avdelningen för klinisk kemi och farmakologi
• Publiceringsår: 2008
• Språk: Engelska
• Sidor: 960-968
• Publikation/Tidskrift/Serie: Chemistry and Biology
• Volym: 15
• Issue: 9
• Länkar: http://www.ncbi.nlm.nih.gov/pubmed/18804033?dopt=Abstract; http://dx.doi.org/10.1016/j.chembiol.2008.07.021
• Dokumenttyp: Artikel i tidskrift
• Förlag: Cell Press
• Ämne: Medicinal Chemistry; Pharmacology and Toxicology
• Status: Published
• ISBN/ISSN/Övrigt: ISSN: 1879-1301