Structure of the streptococcal endopeptidase IdeS, a cysteine proteinase with strict specificity for IgG

Summary, in English

Pathogenic bacteria have developed complex and diverse virulence mechanisms that weaken or disable the host immune defense system. IdeS (IgG-degrading enzyme of Streptococcus pyogenes) is a secreted cysteine endopeptidase from the human pathogen S. pyogenes with an extraordinarily high degree of substrate specificity, catalyzing a single proteolytic cleavage at the lower hinge of human IgG. This proteolytic degradation promotes inhibition of opsonophagocytosis and interferes with the killing of group A Streptococcus. We have determined the crystal structure of the catalytically inactive mutant Ides-C94S by x-ray crystallography at 1.9-Angstrom resolution. Despite negligible sequence homology to known proteinases, the core of the structure resembles the canonical papain fold although with major insertions and a distinct substrate-binding site. Therefore IdeS belongs to a unique family within the CA clan of cysteine proteinases. Based on analogy with inhibitor complexes of papain-like proteinases, we propose a model for substrate binding by IdeS.

• Författare: K Wenig; L Chatwell; U von Pawel-Rammingen; Lars Björck; R Huber; P Sondermann
• Avdelning/ar: Infektionsmedicin
• Publiceringsår: 2004
• Språk: Engelska
• Sidor: 17371-17376
• Publikation/Tidskrift/Serie: Proceedings of the National Academy of Sciences
• Volym: 101
• Issue: 50
• Länkar: http://dx.doi.org/10.1073/pnas.0407965101
• Dokumenttyp: Artikel i tidskrift
• Förlag: National Academy of Sciences
• Ämne: Infectious Medicine
• Nyckelord: streptococcus pyogenes; Mac-1
• Status: Published
• ISBN/ISSN/Övrigt: ISSN: 1091-6490