PDBsum entry 1y08

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Hydrolase PDB id
Protein chain
286 a.a. *
Waters ×206
* Residue conservation analysis
PDB id:
Name: Hydrolase
Title: Structure of the streptococcal endopeptidase ides, a novel cysteine proteinase with strict specificity for igg
Structure: Hypothetical protein spy0861. Chain: a. Fragment: residues 49-339. Synonym: ides, igg-degrading enzyme. Engineered: yes. Mutation: yes
Source: Streptococcus pyogenes. Organism_taxid: 1314. Expressed in: escherichia coli. Expression_system_taxid: 562.
1.93Å     R-factor:   0.196     R-free:   0.235
Authors: K.Wenig,L.Chatwell,U.Von Pawel-Rammingen,L.Bjoerck,R.Huber, P.Sondermann
Key ref:
K.Wenig et al. (2004). Structure of the streptococcal endopeptidase IdeS, a cysteine proteinase with strict specificity for IgG. Proc Natl Acad Sci U S A, 101, 17371-17376. PubMed id: 15574492 DOI: 10.1073/pnas.0407965101
15-Nov-04     Release date:   21-Dec-04    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
Q9F1R7  (Q9F1R7_STRPY) -  Sib38
339 a.a.
286 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)


DOI no: 10.1073/pnas.0407965101 Proc Natl Acad Sci U S A 101:17371-17376 (2004)
PubMed id: 15574492  
Structure of the streptococcal endopeptidase IdeS, a cysteine proteinase with strict specificity for IgG.
K.Wenig, L.Chatwell, U.von Pawel-Rammingen, L.Björck, R.Huber, P.Sondermann.
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.
  Selected figure(s)  
Figure 2.
Fig. 2. Comparison of IdeS-C94S (yellow), papain (green) (Protein Data Bank ID code 1POP [PDB] ), and cathepsin B (purple) (Protein Data Bank ID code 1CSB [PDB] ) active sites. The figure was prepared by superposition of papain and cathepsin B on IdeS and fitting the active-site cysteines on residue 94 of IdeS-C94S.
Figure 3.
Fig. 3. Ball-and-stick model of the catalytic triad of IdeS-C94S with the initial F[obs] - F[calc] electron density map. This difference in electron density, contoured at 2.5 , presumably accounts for a sulfate ion from the crystallization liquid.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19653112 C.A.Penno, Y.Kawabe, A.Ito, and M.Kamihira (2010).
Production of recombinant human erythropoietin/Fc fusion protein by genetically manipulated chickens.
  Transgenic Res, 19, 187-195.  
19948837 C.Hyams, E.Camberlein, J.M.Cohen, K.Bax, and J.S.Brown (2010).
The Streptococcus pneumoniae capsule inhibits complement activity and neutrophil phagocytosis by multiple mechanisms.
  Infect Immun, 78, 704-715.  
19948838 C.Hyams, J.Yuste, K.Bax, E.Camberlein, J.N.Weiser, and J.S.Brown (2010).
Streptococcus pneumoniae resistance to complement-mediated immunity is dependent on the capsular serotype.
  Infect Immun, 78, 716-725.  
19506910 K.S.Nandakumar (2010).
Pathogenic antibody recognition of cartilage.
  Cell Tissue Res, 339, 213-220.  
19737105 R.J.Olsen, and J.M.Musser (2010).
Molecular pathogenesis of necrotizing fasciitis.
  Annu Rev Pathol, 5, 1.  
20219834 R.Yang, M.A.Otten, T.Hellmark, M.Collin, L.Björck, M.H.Zhao, M.R.Daha, and M.Segelmark (2010).
Successful treatment of experimental glomerulonephritis with IdeS and EndoS, IgG-degrading streptococcal enzymes.
  Nephrol Dial Transplant, 25, 2479-2486.  
19935806 P.I.Bird, J.A.Trapani, and J.A.Villadangos (2009).
Endolysosomal proteases and their inhibitors in immunity.
  Nat Rev Immunol, 9, 871-882.  
19815504 R.J.Brezski, O.Vafa, D.Petrone, S.H.Tam, G.Powers, M.H.Ryan, J.L.Luongo, A.Oberholtzer, D.M.Knight, and R.E.Jordan (2009).
Tumor-associated and microbial proteases compromise host IgG effector functions by a single cleavage proximal to the hinge.
  Proc Natl Acad Sci U S A, 106, 17864-17869.  
18301769 B.P.Johansson, O.Shannon, and L.Björck (2008).
IdeS: a bacterial proteolytic enzyme with therapeutic potential.
  PLoS ONE, 3, e1692.  
18332209 J.J.Söderberg, P.Engström, and U.von Pawel-Rammingen (2008).
The intrinsic immunoglobulin g endopeptidase activity of streptococcal Mac-2 proteins implies a unique role for the enzymatically impaired Mac-2 protein of M28 serotype strains.
  Infect Immun, 76, 2183-2188.  
17993455 N.Mallorquí-Fernández, S.P.Manandhar, G.Mallorquí-Fernández, I.Usón, K.Wawrzonek, T.Kantyka, M.Solà, I.B.Thøgersen, J.J.Enghild, J.Potempa, and F.X.Gomis-Rüth (2008).
A new autocatalytic activation mechanism for cysteine proteases revealed by Prevotella intermedia interpain A.
  J Biol Chem, 283, 2871-2882.
PDB codes: 3bb7 3bba
18418689 O.Riess, U.Rüb, A.Pastore, P.Bauer, and L.Schöls (2008).
SCA3: Neurological features, pathogenesis and animal models.
  Cerebellum, 7, 125-137.  
17543400 J.L.Hess, E.A.Porsch, C.A.Shertz, and M.D.Boyle (2007).
Immunoglobulin cleavage by the streptococcal cysteine protease IdeS can be detected using protein G capture and mass spectrometry.
  J Microbiol Methods, 70, 284-291.  
17907170 K.S.Nandakumar, B.P.Johansson, L.Björck, and R.Holmdahl (2007).
Blocking of experimental arthritis by cleavage of IgG antibodies in vivo.
  Arthritis Rheum, 56, 3253-3260.  
16287140 J.Bielnicki, Y.Devedjiev, U.Derewenda, Z.Dauter, A.Joachimiak, and Z.S.Derewenda (2006).
B. subtilis ykuD protein at 2.0 A resolution: insights into the structure and function of a novel, ubiquitous family of bacterial enzymes.
  Proteins, 62, 144-151.
PDB code: 1y7m
16369006 P.Akesson, L.Moritz, M.Truedsson, B.Christensson, and U.von Pawel-Rammingen (2006).
IdeS, a highly specific immunoglobulin G (IgG)-cleaving enzyme from Streptococcus pyogenes, is inhibited by specific IgG antibodies generated during infection.
  Infect Immun, 74, 497-503.  
16339904 D.Vivares, P.Arnoux, and D.Pignol (2005).
A papain-like enzyme at work: native and acyl-enzyme intermediate structures in phytochelatin synthesis.
  Proc Natl Acad Sci U S A, 102, 18848-18853.
PDB codes: 2btw 2bu3
16020535 G.Nicastro, R.P.Menon, L.Masino, P.P.Knowles, N.Q.McDonald, and A.Pastore (2005).
The solution structure of the Josephin domain of ataxin-3: structural determinants for molecular recognition.
  Proc Natl Acad Sci U S A, 102, 10493-10498.
PDB code: 1yzb
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB codes are shown on the right.