Structure of the streptococcal endopeptidase IdeS, a cysteine proteinase with strict specificity for IgG
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/258247
- author
- Wenig, K ; Chatwell, L ; von Pawel-Rammingen, U ; Björck, Lars LU ; Huber, R and Sondermann, P
- organization
- publishing date
- 2004
- 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 Academy of 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
- 2016-04-01 12:25:47
- date last changed
- 2022-03-05 23:27:34
@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}},
keywords = {{streptococcus pyogenes; Mac-1}},
language = {{eng}},
number = {{50}},
pages = {{17371--17376}},
publisher = {{National Academy of 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}},
doi = {{10.1073/pnas.0407965101}},
volume = {{101}},
year = {{2004}},
}