title: Structure of the streptococcal endopeptidase IdeS, a cysteine proteinase with strict specificity for IgG.
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-A 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.
authors.affiliation: Department of Structural Research, Max Planck Institute for Biochemistry, D-82152 Martinsried, Germany. wenig@biochem.mpg.de
authors.forename: Katja
authors.initials: K
authors.lastname: Wenig
authors.forename: Lorenz
authors.initials: L
authors.lastname: Chatwell
authors.forename: Ulrich
authors.initials: U
authors.lastname: von Pawel-Rammingen
authors.forename: Lars
authors.initials: L
authors.lastname: Björck
authors.forename: Robert
authors.initials: R
authors.lastname: Huber
authors.forename: Peter
authors.initials: P
authors.lastname: Sondermann
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D002384:Catalysis; D018360:Crystallography, X-Ray; D003545:Cysteine / Q000235:genetics / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D007141:Immunoglobulin Fc Fragments / Q000737:chemistry / Q000378:metabolism; D007074:Immunoglobulin G / Q000737:chemistry / Q000378:metabolism*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010206:Papain / Q000737:chemistry / Q000378:metabolism; D017434:Protein Structure, Tertiary; D016415:Sequence Alignment; D013297:Streptococcus pyogenes / Q000201:enzymology* / Q000235:genetics; D013379:Substrate Specificity
chemical_list: D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D003546:Cysteine Endopeptidases; D010206:Papain; D003545:Cysteine