3W09

Influenza virus neuraminidase subtype N9 (TERN) complexed with 2,3-dif guanidino-neu5ac2en inhibitor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.189 
  • R-Value Work: 0.144 
  • R-Value Observed: 0.146 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 2.1 of the entry. See complete history


Literature

Mechanism-based covalent neuraminidase inhibitors with broad-spectrum influenza antiviral activity

Kim, J.-H.Resende, R.Wennekes, T.Chen, H.M.Bance, N.Buchini, S.Watts, A.G.Pilling, P.Streltsov, V.A.Petric, M.Liggins, R.Barrett, S.McKimm-Breschkin, J.L.Niikura, M.Withers, S.G.

(2013) Science 340: 71-75

  • DOI: https://doi.org/10.1126/science.1232552
  • Primary Citation of Related Structures:  
    3W09

  • PubMed Abstract: 

    Influenza antiviral agents play important roles in modulating disease severity and in controlling pandemics while vaccines are prepared, but the development of resistance to agents like the commonly used neuraminidase inhibitor oseltamivir may limit their future utility. We report here on a new class of specific, mechanism-based anti-influenza drugs that function through the formation of a stabilized covalent intermediate in the influenza neuraminidase enzyme, and we confirm this mode of action with structural and mechanistic studies. These compounds function in cell-based assays and in animal models, with efficacies comparable to that of the neuraminidase inhibitor zanamivir and with broad-spectrum activity against drug-resistant strains in vitro. The similarity of their structure to that of the natural substrate and their mechanism-based design make these attractive antiviral candidates.


  • Organizational Affiliation

    Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, British Columbia V6T 1Z1, Canada.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Neuraminidase388Influenza A virus (A/tern/Australia/G70C/1975(H11N9))Mutation(s): 0 
EC: 3.2.1.18
UniProt
Find proteins for P03472 (Influenza A virus (strain A/Tern/Australia/G70C/1975 H11N9))
Explore P03472 
Go to UniProtKB:  P03472
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP03472
Sequence Annotations
Expand
  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-2)-alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-6)]beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
B
9N-Glycosylation
Glycosylation Resources
GlyTouCan:  G68668TB
GlyCosmos:  G68668TB
GlyGen:  G68668TB
Entity ID: 3
MoleculeChains Length2D Diagram Glycosylation3D Interactions
2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
C
2N-Glycosylation
Glycosylation Resources
GlyTouCan:  G42666HT
GlyCosmos:  G42666HT
GlyGen:  G42666HT
Small Molecules
Ligands 4 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ZGE
Query on ZGE

Download Ideal Coordinates CCD File 
L [auth A]5-acetamido-2,6-anhydro-4-carbamimidamido-3,4,5-trideoxy-3-fluoro-D-glycero-D-galacto-non-2-enonic acid
C12 H19 F N4 O7
UCGICVWHWQNCDB-NSNFAWTCSA-N
NAG
Query on NAG

Download Ideal Coordinates CCD File 
D [auth A]2-acetamido-2-deoxy-beta-D-glucopyranose
C8 H15 N O6
OVRNDRQMDRJTHS-FMDGEEDCSA-N
GOL
Query on GOL

Download Ideal Coordinates CCD File 
E [auth A]
F [auth A]
G [auth A]
H [auth A]
I [auth A]
E [auth A],
F [auth A],
G [auth A],
H [auth A],
I [auth A],
J [auth A],
K [auth A]
GLYCEROL
C3 H8 O3
PEDCQBHIVMGVHV-UHFFFAOYSA-N
CA
Query on CA

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

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.00 Å
  • R-Value Free: 0.189 
  • R-Value Work: 0.144 
  • R-Value Observed: 0.146 
  • Space Group: I 4 3 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 180.836α = 90
b = 180.836β = 90
c = 180.836γ = 90
Software Package:
Software NamePurpose
Blu-Icedata collection
PHASERphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-05-01
    Type: Initial release
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Atomic model, Data collection, Derived calculations, Structure summary
  • Version 2.1: 2023-11-08
    Changes: Data collection, Database references, Refinement description, Structure summary