Structure of the streptococcal endopeptidase IdeS, a cysteine proteinase with strict specificity for IgG
Författare
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.
Avdelning/ar
Publiceringsår
2004
Språk
Engelska
Sidor
17371-17376
Publikation/Tidskrift/Serie
Proceedings of the National Academy of Sciences
Volym
101
Issue
50
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