4E76

Apo crystal structure of HCV NS5B genotype 2A JFH-1 isolate with beta hairpin loop deletion


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.257 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.215 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Structure of hepatitis C virus polymerase in complex with primer-template RNA.

Mosley, R.T.Edwards, T.E.Murakami, E.Lam, A.M.Grice, R.L.Du, J.Sofia, M.J.Furman, P.A.Otto, M.J.

(2012) J Virol 86: 6503-6511

  • DOI: https://doi.org/10.1128/JVI.00386-12
  • Primary Citation of Related Structures:  
    4E76, 4E78, 4E7A

  • PubMed Abstract: 

    The replication of the hepatitis C viral (HCV) genome is accomplished by the NS5B RNA-dependent RNA polymerase (RdRp), for which mechanistic understanding and structure-guided drug design efforts have been hampered by its propensity to crystallize in a closed, polymerization-incompetent state. The removal of an autoinhibitory β-hairpin loop from genotype 2a HCV NS5B increases de novo RNA synthesis by >100-fold, promotes RNA binding, and facilitated the determination of the first crystallographic structures of HCV polymerase in complex with RNA primer-template pairs. These crystal structures demonstrate the structural realignment required for primer-template recognition and elongation, provide new insights into HCV RNA synthesis at the molecular level, and may prove useful in the structure-based design of novel antiviral compounds. Additionally, our approach for obtaining the RNA primer-template-bound structure of HCV polymerase may be generally applicable to solving RNA-bound complexes for other viral RdRps that contain similar regulatory β-hairpin loops, including bovine viral diarrhea virus, dengue virus, and West Nile virus.


  • Organizational Affiliation

    Pharmasset Inc, Princeton, New Jersey, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
RNA-directed RNA polymerase572Hepatitis C virus JFH-1Mutation(s): 2 
Gene Names: NS5B
EC: 2.7.7.48
UniProt
Find proteins for Q99IB8 (Hepatitis C virus genotype 2a (isolate JFH-1))
Explore Q99IB8 
Go to UniProtKB:  Q99IB8
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ99IB8
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.257 
  • R-Value Work: 0.213 
  • R-Value Observed: 0.215 
  • Space Group: P 65
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 140.69α = 90
b = 140.69β = 90
c = 92.63γ = 120
Software Package:
Software NamePurpose
XSCALEdata scaling
PHASERphasing
REFMACrefinement
PDB_EXTRACTdata extraction
XDSdata reduction

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-04-18
    Type: Initial release
  • Version 1.1: 2012-04-25
    Changes: Database references
  • Version 1.2: 2012-06-06
    Changes: Database references
  • Version 1.3: 2017-07-26
    Changes: Refinement description, Source and taxonomy
  • Version 1.4: 2023-09-13
    Changes: Data collection, Database references, Derived calculations, Refinement description