2J7U

Dengue virus NS5 RNA dependent RNA polymerase domain


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.201 

Starting Model: experimental
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wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Crystal Structure of the Dengue Virus RNA- Dependent RNA Polymerase Catalytic Domain at 1.85 Angstrom Resolution.

Yap, T.L.Xu, T.Chen, Y.L.Malet, H.Egloff, M.P.Canard, B.Vasudevan, S.G.Lescar, J.

(2007) J Virol 81: 4753

  • DOI: https://doi.org/10.1128/JVI.02283-06
  • Primary Citation of Related Structures:  
    2J7U, 2J7W

  • PubMed Abstract: 

    Dengue fever, a neglected emerging disease for which no vaccine or antiviral agents exist at present, is caused by dengue virus, a member of the Flavivirus genus, which includes several important human pathogens, such as yellow fever and West Nile viruses. The NS5 protein from dengue virus is bifunctional and contains 900 amino acids. The S-adenosyl methionine transferase activity resides within its N-terminal domain, and residues 270 to 900 form the RNA-dependent RNA polymerase (RdRp) catalytic domain. Viral replication begins with the synthesis of minus-strand RNA from the dengue virus positive-strand RNA genome, which is subsequently used as a template for synthesizing additional plus-strand RNA genomes. This essential function for the production of new viral particles is catalyzed by the NS5 RdRp. Here we present a high-throughput in vitro assay partly recapitulating this activity and the crystallographic structure of an enzymatically active fragment of the dengue virus RdRp refined at 1.85-A resolution. The NS5 nuclear localization sequences, previously thought to fold into a separate domain, form an integral part of the polymerase subdomains. The structure also reveals the presence of two zinc ion binding motifs. In the absence of a template strand, a chain-terminating nucleoside analogue binds to the priming loop site. These results should inform and accelerate the structure-based design of antiviral compounds against dengue virus.


  • Organizational Affiliation

    Novartis Institute for Tropical Diseases, 05-01 Chromos, 10 Biopolis Road, Singapore 138670, Singapore.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
RNA DEPENDENT RNA POLYMERASE635Dengue virusMutation(s): 0 
UniProt
Find proteins for Q6YMS4 (Dengue virus type 3 (strain Sri Lanka/1266/2000))
Explore Q6YMS4 
Go to UniProtKB:  Q6YMS4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6YMS4
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.85 Å
  • R-Value Free: 0.234 
  • R-Value Work: 0.200 
  • R-Value Observed: 0.201 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 160.15α = 90
b = 180.478β = 90
c = 57.987γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
SCALEPACKdata scaling
AMoREphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-03-13
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Refinement description, Version format compliance
  • Version 1.2: 2023-12-13
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description