The human protease inhibitor cystatin C is an activating cofactor for the streptococcal cysteine protease IdeS
2008 (English)In: Chemistry and Biology, ISSN 1074-5521, E-ISSN 1879-1301, Vol. 15, no 9, 960-968 p.Article in journal (Refereed) Published
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.
Place, publisher, year, edition, pages
2008. Vol. 15, no 9, 960-968 p.
Chembio; microbio; proteins
Cell and Molecular Biology
IdentifiersURN: urn:nbn:se:umu:diva-20793DOI: 10.1016/j.chembiol.2008.07.021ISI: 000259918200011PubMedID: 18804033OAI: oai:DiVA.org:umu-20793DiVA: diva2:209562