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

Wenig, K; Chatwell, L; von Pawel-Rammingen, U; Björck, Lars LU ; Huber, R and Sondermann, P (2004) In Proceedings of the National Academy of Sciences 101(50). p.17371-17376
Abstract
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
streptococcus pyogenes, Mac-1
in
Proceedings of the National Academy of Sciences
volume
101
issue
50
pages
17371 - 17376
publisher
National Acad Sciences
external identifiers
  • wos:000225803400013
  • scopus:10644265996
ISSN
1091-6490
DOI
10.1073/pnas.0407965101
language
English
LU publication?
yes
id
03e534f0-0701-4163-8b83-5dee07f1cccc (old id 258247)
date added to LUP
2007-11-05 13:24:06
date last changed
2017-08-27 04:18:42
@article{03e534f0-0701-4163-8b83-5dee07f1cccc,
  abstract     = {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.},
  author       = {Wenig, K and Chatwell, L and von Pawel-Rammingen, U and Björck, Lars and Huber, R and Sondermann, P},
  issn         = {1091-6490},
  keyword      = {streptococcus pyogenes,Mac-1},
  language     = {eng},
  number       = {50},
  pages        = {17371--17376},
  publisher    = {National Acad Sciences},
  series       = {Proceedings of the National Academy of Sciences},
  title        = {Structure of the streptococcal endopeptidase IdeS, a cysteine proteinase with strict specificity for IgG},
  url          = {http://dx.doi.org/10.1073/pnas.0407965101},
  volume       = {101},
  year         = {2004},
}