4NUY

Crystal structure of EndoS, an endo-beta-N-acetyl-glucosaminidase from Streptococcus pyogenes


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.61 Å
  • R-Value Free: 0.263 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.215 

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This is version 1.2 of the entry. See complete history


Literature

Crystal structure of Streptococcus pyogenes EndoS, an immunomodulatory endoglycosidase specific for human IgG antibodies.

Trastoy, B.Lomino, J.V.Pierce, B.G.Carter, L.G.Gunther, S.Giddens, J.P.Snyder, G.A.Weiss, T.M.Weng, Z.Wang, L.X.Sundberg, E.J.

(2014) Proc Natl Acad Sci U S A 111: 6714-6719

  • DOI: https://doi.org/10.1073/pnas.1322908111
  • Primary Citation of Related Structures:  
    4NUY, 4NUZ

  • PubMed Abstract: 

    To evade host immune mechanisms, many bacteria secrete immunomodulatory enzymes. Streptococcus pyogenes, one of the most common human pathogens, secretes a large endoglycosidase, EndoS, which removes carbohydrates in a highly specific manner from IgG antibodies. This modification renders antibodies incapable of eliciting host effector functions through either complement or Fc γ receptors, providing the bacteria with a survival advantage. On account of this antibody-specific modifying activity, EndoS is being developed as a promising injectable therapeutic for autoimmune diseases that rely on autoantibodies. Additionally, EndoS is a key enzyme used in the chemoenzymatic synthesis of homogenously glycosylated antibodies with tailored Fc γ receptor-mediated effector functions. Despite the tremendous utility of this enzyme, the molecular basis of EndoS specificity for, and processing of, IgG antibodies has remained poorly understood. Here, we report the X-ray crystal structure of EndoS and provide a model of its encounter complex with its substrate, the IgG1 Fc domain. We show that EndoS is composed of five distinct protein domains, including glycosidase, leucine-rich repeat, hybrid Ig, carbohydrate binding module, and three-helix bundle domains, arranged in a distinctive V-shaped conformation. Our data suggest that the substrate enters the concave interior of the enzyme structure, is held in place by the carbohydrate binding module, and that concerted conformational changes in both enzyme and substrate are required for subsequent antibody deglycosylation. The EndoS structure presented here provides a framework from which novel endoglycosidases could be engineered for additional clinical and biotechnological applications.


  • Organizational Affiliation

    Institute of Human Virology and Departments of Biochemistry and Molecular Biology, Medicine, and Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Endo-beta-N-acetylglucosaminidase F2899Streptococcus pyogenes serotype M1Mutation(s): 0 
Gene Names: endoSM5005_Spy1540
EC: 3.2.1.96
UniProt
Find proteins for Q99Y92 (Streptococcus pyogenes serotype M1)
Explore Q99Y92 
Go to UniProtKB:  Q99Y92
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ99Y92
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CA
Query on CA

Download Ideal Coordinates CCD File 
B [auth A]CALCIUM ION
Ca
BHPQYMZQTOCNFJ-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.61 Å
  • R-Value Free: 0.263 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.215 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 92.388α = 90
b = 94.65β = 90
c = 142.92γ = 90
Software Package:
Software NamePurpose
XSCALEdata scaling
PHASERphasing
PHENIXrefinement
PDB_EXTRACTdata extraction
JBluIce-EPICSdata collection
XDSdata reduction

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2014-04-09
    Type: Initial release
  • Version 1.1: 2014-05-21
    Changes: Database references
  • Version 1.2: 2024-02-28
    Changes: Data collection, Database references, Derived calculations