1IVB

STRUCTURES OF AROMATIC INHIBITORS OF INFLUENZA VIRUS NEURAMINIDASE


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Work: 0.189 
  • R-Value Observed: 0.189 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structures of aromatic inhibitors of influenza virus neuraminidase.

Jedrzejas, M.J.Singh, S.Brouillette, W.J.Laver, W.G.Air, G.M.Luo, M.

(1995) Biochemistry 34: 3144-3151

  • DOI: https://doi.org/10.1021/bi00010a003
  • Primary Citation of Related Structures:  
    1IVB, 1IVC, 1IVD, 1IVE, 1IVF, 1IVG

  • PubMed Abstract: 

    Neuraminidase (NA), a surface glycoprotein of influenza virus, is a potential target for design of antiinfluenza agents. The crystal structure of influenza virus neuraminidase showed that in the active site 11 residues are universally conserved among all strains known so far. Several potent inhibitors based on the carbohydrate compound 2-deoxy-2,3-didehydro-D-N-acetylneuraminic acid (DANA) have been shown to bind to the conserved active site and to reduce virus infection in animals when administered by nasal spray. Inhibitors of this type are, however, rapidly excreted from physiological systems and may not be effective in order to provide long-time protection. A new class of specific NA inhibitors, which are benzoic acid derivatives, has been designed on the basis of the three-dimensional structure of the NA-DANA complex and modeling of derivatives of 4-(acetylamino)benzoic acid in the NA active site. Intermediates were synthesized and were shown to moderately inhibit the NA activity and to bind to the NA active site as predicted. These rudimentary inhibitors, 4-(acetylamino)-3-hydroxy-5-nitrobenzoic acid, 4-(acetylamino)-3-hydroxy-5-aminobenzoic acid, and 4-(acetylamino)-3-aminobenzoic acid, and their X-ray structures in complexes with N2 (A/Tokyo/3/67) and B/Lee/40 neuraminidases have been analyzed. The coordinates of such inhibitors complexed with NA were used as the starting model for further design of more potent benzoic acid inhibitors. Because the active site residues of NA are invariant, the designed aromatic inhibitors have the potential to become an antiviral drug against all strains of influenza virus.


  • Organizational Affiliation

    Department of Microbiology, University of Alabama at Birmingham 35294.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
INFLUENZA VIRUS B/LEE/40 NEURAMINIDASE390Influenza B virusMutation(s): 0 
EC: 3.2.1.18
UniProt
Find proteins for P03474 (Influenza B virus (strain B/Lee/1940))
Explore P03474 
Go to UniProtKB:  P03474
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP03474
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Work: 0.189 
  • R-Value Observed: 0.189 
  • Space Group: P 4 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 124.54α = 90
b = 124.54β = 90
c = 71.82γ = 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: 1995-03-31
    Type: Initial release
  • Version 1.1: 2008-03-03
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Derived calculations, Version format compliance
  • Version 1.3: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Data collection, Database references, Derived calculations, Other, Structure summary