2YA6

Crystal structure of Streptococcus pneumoniae NanA (TIGR4) in complex with DANA


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.197 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Structural Basis for Streptococcus Pneumoniae Nana Inhibition by Influenza Antivirals Zanamivir and Oseltamivir Carboxylate.

Gut, H.Xu, G.Taylor, G.L.Walsh, M.A.

(2011) J Mol Biol 409: 496

  • DOI: https://doi.org/10.1016/j.jmb.2011.04.016
  • Primary Citation of Related Structures:  
    2YA4, 2YA5, 2YA6, 2YA7, 2YA8

  • PubMed Abstract: 

    The human pathogen Streptococcus pneumoniae is the major cause of bacterial meningitis, respiratory tract infection, septicemia, and otitis media. The bacterium expresses neuraminidase (NA) proteins that contribute to pathogenesis by cleaving sialic acids from host glycoconjugates, thereby enhancing biofilm formation and colonization. Recent in vivo experiments have shown that antiviral compounds, widely used in clinics and designed to inhibit influenza NA, significantly reduce biofilm formation and nasopharyngeal colonization of S. pneumoniae in mice. Here, we present the structural basis for the beneficial effect of these compounds against pneumococcal infection. Crystal structures of pneumococcal NanA in complex with zanamivir and oseltamivir carboxylate are discussed, correlated with measured inhibitory constants K(i), and compared with the binding modes of the inhibitors in the viral enzyme. Inhibitor structures show for the first time how clinically approved anti-influenza compounds interact with an NA of the human pathogen S. pneumoniae and give a rational explanation for their antibacterial effects.


  • Organizational Affiliation

    MRC France, BM14 c/o ESRF, 6 rue Jules Horowitz, BP220, 38043 Grenoble, France. [email protected]


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
NEURAMINIDASE A
A, B
493Streptococcus pneumoniae TIGR4Mutation(s): 0 
EC: 3.2.1.18
UniProt
Find proteins for P62575 (Streptococcus pneumoniae)
Explore P62575 
Go to UniProtKB:  P62575
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP62575
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 3 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
DAN
Query on DAN

Download Ideal Coordinates CCD File 
C [auth A],
H [auth B]
2-DEOXY-2,3-DEHYDRO-N-ACETYL-NEURAMINIC ACID
C11 H17 N O8
JINJZWSZQKHCIP-UFGQHTETSA-N
FMT
Query on FMT

Download Ideal Coordinates CCD File 
D [auth A],
F [auth A],
G [auth A],
J [auth B],
K [auth B]
FORMIC ACID
C H2 O2
BDAGIHXWWSANSR-UHFFFAOYSA-N
CL
Query on CL

Download Ideal Coordinates CCD File 
E [auth A],
I [auth B]
CHLORIDE ION
Cl
VEXZGXHMUGYJMC-UHFFFAOYSA-M
Binding Affinity Annotations 
IDSourceBinding Affinity
DAN PDBBind:  2YA6 Ki: 2000 (nM) from 1 assay(s)
BindingDB:  2YA6 Ki: 1600 (nM) from 1 assay(s)
IC50: min: 4800, max: 1.00e+4 (nM) from 2 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.238 
  • R-Value Work: 0.196 
  • R-Value Observed: 0.197 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 164.857α = 90
b = 48.835β = 104.13
c = 125.383γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-04-27
    Type: Initial release
  • Version 1.1: 2011-06-02
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Other
  • Version 1.4: 2020-09-02
    Changes: Derived calculations, Structure summary
  • Version 1.5: 2024-05-08
    Changes: Data collection, Database references