1INW

A SIALIC ACID DERIVED PHOSPHONATE ANALOG INHIBITS DIFFERENT STRAINS OF INFLUENZA VIRUS NEURAMINIDASE WITH DIFFERENT EFFICIENCIES


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Work: 0.206 
  • R-Value Observed: 0.206 

wwPDB Validation   3D Report Full Report


This is version 2.0 of the entry. See complete history


Literature

A sialic acid-derived phosphonate analog inhibits different strains of influenza virus neuraminidase with different efficiencies.

White, C.L.Janakiraman, M.N.Laver, W.G.Philippon, C.Vasella, A.Air, G.M.Luo, M.

(1995) J Mol Biol 245: 623-634

  • Primary Citation of Related Structures:  
    1INV, 1INW, 1INX, 1INY

  • PubMed Abstract: 

    A phosphonate analog of N-acetyl neuraminic acid (PANA) has been designed as a potential neuraminidase (NA) inhibitor and synthesized as both the alpha (ePANA) and beta (aPANA) anomers. Inhibition of type A (N2) and type B NA activity by ePANA was approximately a 100-fold better than by sialic acid, but inhibition of type A (N9) NA was only ten-fold better than by sialic acid. The aPANA compound was not a strong inhibitor for any of the NA strains tested. The crystal structures at 2.4 A resolution of ePANA complexed to type A (N2) NA, type A (N9) NA and type B NA and aPANA complexed to type A (N2) NA showed that neither of the PANA compounds distorted the NA active site upon binding. No significant differences in the NA-ePANA complex structures were found to explain the anomalous inhibition of N9 neuraminidase by ePANA. We put forward the hypothesis that an increase in the ePANA inhibition compared to that caused by sialic acid is due to (1) a stronger electrostatic interaction between the inhibitor phosphonyl group and the active site arginine pocket and (2) a lower distortion energy requirement for binding of ePANA.


  • Organizational Affiliation

    Center for Macromolecular Crystallography, University of Alabama at Birmingham 35294.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
INFLUENZA A SUBTYPE N2 NEURAMINIDASE388Influenza A virusMutation(s): 0 
EC: 3.2.1.18
UniProt
Find proteins for P06820 (Influenza A virus (strain A/Tokyo/3/1967 H2N2))
Explore P06820 
Go to UniProtKB:  P06820
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP06820
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

Help

Entity ID: 2
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-mannopyranose-(1-3)-[alpha-D-mannopyranose-(1-6)]alpha-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose
B
5N-Glycosylation
Glycosylation Resources
GlyTouCan:  G21381MC
GlyCosmos:  G21381MC
GlyGen:  G21381MC
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Work: 0.206 
  • R-Value Observed: 0.206 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 122.08α = 90
b = 141.67β = 90
c = 141.87γ = 90
Software Package:
Software NamePurpose
X-PLORmodel building
X-PLORrefinement
X-PLORphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 1995-02-07
    Type: Initial release
  • Version 1.1: 2008-03-03
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Database references, Derived calculations, Other, Structure summary