4YW3

Crystal Structure of Streptococcus pneumoniae NanC, complex with Neu5Ac and Neu5Ac2en following soaking with Neu5Ac2en


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.203 
  • R-Value Work: 0.172 
  • R-Value Observed: 0.173 

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Ligand Structure Quality Assessment 


This is version 2.3 of the entry. See complete history


Literature

Streptococcus pneumoniae NanC: STRUCTURAL INSIGHTS INTO THE SPECIFICITY AND MECHANISM OF A SIALIDASE THAT PRODUCES A SIALIDASE INHIBITOR.

Owen, C.D.Lukacik, P.Potter, J.A.Sleator, O.Taylor, G.L.Walsh, M.A.

(2015) J Biol Chem 290: 27736-27748

  • DOI: https://doi.org/10.1074/jbc.M115.673632
  • Primary Citation of Related Structures:  
    4YW1, 4YW2, 4YW3, 4YW5, 4YZ1, 4YZ2, 4YZ4, 4YZ5, 5F9T

  • PubMed Abstract: 

    Streptococcus pneumoniae is an important human pathogen that causes a range of disease states. Sialidases are important bacterial virulence factors. There are three pneumococcal sialidases: NanA, NanB, and NanC. NanC is an unusual sialidase in that its primary reaction product is 2-deoxy-2,3-didehydro-N-acetylneuraminic acid (Neu5Ac2en, also known as DANA), a nonspecific hydrolytic sialidase inhibitor. The production of Neu5Ac2en from α2-3-linked sialosides by the catalytic domain is confirmed within a crystal structure. A covalent complex with 3-fluoro-β-N-acetylneuraminic acid is also presented, suggesting a common mechanism with other sialidases up to the final step of product formation. A conformation change in an active site hydrophobic loop on ligand binding constricts the entrance to the active site. In addition, the distance between the catalytic acid/base (Asp-315) and the ligand anomeric carbon is unusually short. These features facilitate a novel sialidase reaction in which the final step of product formation is direct abstraction of the C3 proton by the active site aspartic acid, forming Neu5Ac2en. NanC also possesses a carbohydrate-binding module, which is shown to bind α2-3- and α2-6-linked sialosides, as well as N-acetylneuraminic acid, which is captured in the crystal structure following hydration of Neu5Ac2en by NanC. Overall, the pneumococcal sialidases show remarkable mechanistic diversity while maintaining a common structural scaffold.


  • Organizational Affiliation

    From the Biomedical Sciences Research Complex, University of St. Andrews, St. Andrews, Fife KY16 9ST, United Kingdom.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Neuraminidase C
A, B
659Streptococcus pneumoniae TIGR4Mutation(s): 0 
Gene Names: SP_1326nanC
EC: 3.2.1.18
UniProt
Find proteins for A0A0H2UQE4 (Streptococcus pneumoniae serotype 4 (strain ATCC BAA-334 / TIGR4))
Explore A0A0H2UQE4 
Go to UniProtKB:  A0A0H2UQE4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A0H2UQE4
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
SIA
Query on SIA

Download Ideal Coordinates CCD File 
D [auth A],
H [auth B]
N-acetyl-alpha-neuraminic acid
C11 H19 N O9
SQVRNKJHWKZAKO-YRMXFSIDSA-N
DAN
Query on DAN

Download Ideal Coordinates CCD File 
G [auth B]2-DEOXY-2,3-DEHYDRO-N-ACETYL-NEURAMINIC ACID
C11 H17 N O8
JINJZWSZQKHCIP-UFGQHTETSA-N
PO4
Query on PO4

Download Ideal Coordinates CCD File 
C [auth A]PHOSPHATE ION
O4 P
NBIIXXVUZAFLBC-UHFFFAOYSA-K
GOL
Query on GOL

Download Ideal Coordinates CCD File 
E [auth A],
F [auth A],
I [auth B]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
DAN BindingDB:  4YW3 IC50: 1.00e+6 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.05 Å
  • R-Value Free: 0.203 
  • R-Value Work: 0.172 
  • R-Value Observed: 0.173 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 100.618α = 90
b = 74.729β = 96.35
c = 113.014γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
PHASERphasing
REFMACrefinement
PDB_EXTRACTdata extraction
HKL-2000data reduction

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History & Funding Information

Deposition Data


Funding OrganizationLocationGrant Number
Biotechnology and Biological Sciences Research CouncilUnited KingdomBB/F016778/1

Revision History  (Full details and data files)

  • Version 1.0: 2015-09-23
    Type: Initial release
  • Version 1.1: 2015-11-25
    Changes: Database references
  • Version 2.0: 2017-08-30
    Changes: Atomic model, Author supporting evidence
  • Version 2.1: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Derived calculations, Structure summary
  • Version 2.2: 2021-06-30
    Changes: Database references, Source and taxonomy, Structure summary
  • Version 2.3: 2024-05-08
    Changes: Data collection, Database references, Refinement description