2VP5

Structural Studies of Nucleoside Analog and Feedback Inhibitor Binding to Drosophila Melanogaster Multisubstrate Deoxyribonucleoside Kinase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.273 
  • R-Value Work: 0.234 
  • R-Value Observed: 0.236 

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This is version 1.3 of the entry. See complete history


Literature

Structural Studies of Nucleoside Analog and Feedback Inhibitor Binding to Drosophila Melanogaster Multisubstrate Deoxyribonucleoside Kinase.

Mikkelsen, N.E.Munch-Petersen, B.Eklund, H.

(2008) FEBS J 275: 2151

  • DOI: https://doi.org/10.1111/j.1742-4658.2008.06369.x
  • Primary Citation of Related Structures:  
    2JJ8, 2VP0, 2VP2, 2VP4, 2VP5, 2VP6, 2VP9, 2VQS

  • PubMed Abstract: 

    The Drosophila melanogaster multisubstrate deoxyribonucleoside kinase (dNK; EC 2.7.1.145) has a high turnover rate and a wide substrate range that makes it a very good candidate for gene therapy. This concept is based on introducing a suicide gene into malignant cells in order to activate a prodrug that eventually may kill the cell. To be able to optimize the function of dNK, it is vital to have structural information of dNK complexes. In this study we present crystal structures of dNK complexed with four different nucleoside analogs (floxuridine, brivudine, zidovudine and zalcitabine) and relate them to the binding of substrate and feedback inhibitors. dCTP and dGTP bind with the base in the substrate site, similarly to the binding of the feedback inhibitor dTTP. All nucleoside analogs investigated bound in a manner similar to that of the pyrimidine substrates, with many interactions in common. In contrast, the base of dGTP adopted a syn-conformation to adapt to the available space of the active site.


  • Organizational Affiliation

    Department of Molecular Biology, Swedish University of Agricultural Sciences, Biomedical Center, Uppsala, Sweden.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
DEOXYNUCLEOSIDE KINASE
A, B
230Drosophila melanogasterMutation(s): 0 
EC: 2.7.1.145
UniProt
Find proteins for Q9XZT6 (Drosophila melanogaster)
Explore Q9XZT6 
Go to UniProtKB:  Q9XZT6
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9XZT6
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.30 Å
  • R-Value Free: 0.273 
  • R-Value Work: 0.234 
  • R-Value Observed: 0.236 
  • Space Group: P 21 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 120.616α = 90
b = 62.55β = 90
c = 68.205γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
MOSFLMdata reduction
SCALAdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-04-18
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-12-13
    Changes: Data collection, Database references, Other, Refinement description