2VW1

Crystal structure of the NanB sialidase from Streptococcus pneumoniae


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.39 Å
  • R-Value Free: 0.278 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.196 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Crystal Structure of the Nanb Sialidase from Streptococcus Pneumoniae

Xu, G.Potter, J.A.Russell, R.J.M.Oggioni, M.R.Andrew, P.W.Taylor, G.L.

(2008) J Mol Biol 384: 436

  • DOI: https://doi.org/10.1016/j.jmb.2008.09.032
  • Primary Citation of Related Structures:  
    2VW0, 2VW1, 2VW2

  • PubMed Abstract: 

    The Streptococcus pneumoniae genomes encode up to three sialidases (or neuraminidases), NanA, NanB and NanC, which are believed to be involved in removing sialic acid from host cell surface glycans, thereby promoting colonization of the upper respiratory tract. Here, we present the crystal structure of NanB to 1.7 A resolution derived from a crystal grown in the presence of the buffer Ches (2-N-cyclohexylaminoethanesulfonic acid). Serendipitously, Ches was found bound to NanB at the enzyme active site, and was found to inhibit NanB with a K(i) of approximately 0.5 mM. In addition, we present the structure to 2.4 A resolution of NanB in complex with the transition-state analogue Neu5Ac2en (2-deoxy-2,3-dehydro-N-acetyl neuraminic acid), which inhibits NanB with a K(i) of approximately 0.3 mM. The sulphonic acid group of Ches and carboxylic acid group of Neu5Ac2en interact with the arginine triad of the active site. The cyclohexyl group of Ches binds in the hydrophobic pocket of NanB occupied by the acetamidomethyl group of Neu5Ac2en. The topology around the NanB active site suggests that the enzyme would have a preference for alpha2,3-linked sialoglycoconjugates, which is confirmed by a kinetic analysis of substrate binding. NMR studies also confirm this preference and show that, like the leech sialidase, NanB acts as an intramolecular trans-sialidase releasing Neu2,7-anhydro5Ac. All three pneumoccocal sialidases possess a carbohydrate-binding domain that is predicted to bind sialic acid. These studies provide support for a possible differential role for NanB compared to NanA in pneumococcal virulence.


  • Organizational Affiliation

    Centre for Biomolecular Sciences, University of St Andrews, St Andrews, Fife, KY16 9ST, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
SIALIDASE B697Streptococcus pneumoniaeMutation(s): 0 
EC: 3.2.1.18
UniProt
Find proteins for Q54727 (Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4))
Explore Q54727 
Go to UniProtKB:  Q54727
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ54727
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
DAN
Query on DAN

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

Download Ideal Coordinates CCD File 
C [auth A]GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
DAN PDBBind:  2VW1 Ki: 3.00e+5 (nM) from 1 assay(s)
BindingDB:  2VW1 Ki: 3.30e+5 (nM) from 1 assay(s)
IC50: 1.00e+6 (nM) from 1 assay(s)
Binding MOAD:  2VW1 Ki: 3.00e+5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.39 Å
  • R-Value Free: 0.278 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.196 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 76.597α = 90
b = 82.699β = 90
c = 117.423γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling
AMoREphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-06-24
    Type: Initial release
  • Version 1.1: 2011-05-08
    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: 2023-12-13
    Changes: Data collection, Database references, Refinement description, Structure summary