Structure of the streptococcal endopeptidase IdeS, a cysteine proteinase with strict specificity for IgG
Author
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.
Department/s
Publishing year
2004
Language
English
Pages
17371-17376
Publication/Series
Proceedings of the National Academy of Sciences
Volume
101
Issue
50
Document type
Journal article
Publisher
National Academy of Sciences
Topic
- Infectious Medicine
Keywords
- streptococcus pyogenes
- Mac-1
Status
Published
ISBN/ISSN/Other
- ISSN: 1091-6490