4OR6

Structure of Influenza B PB2 cap-binding domain with Q325F mutation complex with GDP


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.29 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.188 

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This is version 1.2 of the entry. See complete history


Literature

The crystal structure of the PB2 cap-binding domain of influenza B virus reveals a novel cap recognition mechanism.

Liu, Y.Yang, Y.Fan, J.He, R.Luo, M.Zheng, X.

(2015) J Biol Chem 290: 9141-9149

  • DOI: https://doi.org/10.1074/jbc.M115.636464
  • Primary Citation of Related Structures:  
    4OR4, 4OR6, 4Q46

  • PubMed Abstract: 

    The influenza RNA-dependent RNA polymerase is a core enzyme required for both transcription and replication of the virus RNA genome, making it a potential drug target for the influenza virus. To detect the feature of cap-dependent transcription of influenza B virus (FluB) polymerase, we determined the crystal structures of the wild-type FluB polymerase PB2 subunit cap-binding domain (PB2cap) with bound GDP and the mutant FluB Q325F PB2cap with bound m(7)GDP or GDP. These structures revealed that, distinct from influenza A virus (FluA) PB2cap, the guanine and ribose moieties of substrates invert in FluB PB2caps. Moreover, we characterized the substrate specificity and affinity of the PB2caps using isothermal titration calorimetry. FluB PB2cap has a weaker affinity for m(7)GDP than FluA PB2cap. Unlike FluA PB2cap that has a preference for m(7)GDP in comparison with GDP, FluB PB2cap shows an analogous affinity for both substrates. Replacement of FluB PB2 Glu(325) by Phe, the corresponding residue of FluA PB2, increased the binding affinity of FluB PB2cap for m(7)GDP to a level approximate to that of FluA PB2cap and caused a significant higher affinity to GDP. This study indicated that FluB PB2cap has a unique cap recognition mechanism compared with FluA PB2cap, providing molecular insight into inhibitor design targeting FluB PB2cap.


  • Organizational Affiliation

    From the State Key Lab of Protein and Plant Gene Research and Department of Biochemistry and Molecular Biology, School of Life Sciences, Peking University, Beijing 100871, China and.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Polymerase basic protein 2
A, B
169Influenza B virusMutation(s): 0 
UniProt
Find proteins for A0A0J9X1Y8 (Influenza B virus)
Explore A0A0J9X1Y8 
Go to UniProtKB:  A0A0J9X1Y8
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupA0A0J9X1Y8
Sequence Annotations
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  • Reference Sequence
Small Molecules
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.29 Å
  • R-Value Free: 0.246 
  • R-Value Work: 0.185 
  • R-Value Observed: 0.188 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.974α = 90
b = 90.151β = 90
c = 95.706γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
MOLREPphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling
PHENIXrefinement

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-02-25
    Type: Initial release
  • Version 1.1: 2019-12-25
    Changes: Database references
  • Version 1.2: 2023-11-08
    Changes: Data collection, Database references, Derived calculations, Refinement description