1HIY

Binding of nucleotides to NDP kinase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.325 
  • R-Value Work: 0.220 
  • R-Value Observed: 0.220 

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Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Binding of Nucleotides to Nucleoside Diphosphate Kinase: A Calorimetric Study.

Cervoni, L.Lascu, I.Xu, Y.Gonin, P.Morr, M.Merouani, M.Janin, J.Giartosio, A.

(2001) Biochemistry 40: 4583

  • DOI: https://doi.org/10.1021/bi002432s
  • Primary Citation of Related Structures:  
    1HIY

  • PubMed Abstract: 

    The source of affinity for substrates of human nucleoside diphosphate (NDP) kinases is particularly important in that its knowledge could be used to design more effective antiviral nucleoside drugs (e.g., AZT). We carried out a microcalorimetric study of the binding of enzymes from two organisms to various nucleotides. Isothermal titration calorimetry has been used to characterize the binding in terms of Delta G degrees, Delta H degrees and Delta S degrees. Thermodynamic parameters of the interaction of ADP with the hexameric NDP kinase from Dictyostelium discoideum and with the tetrameric enzyme from Myxococcus xanthus, at 20 degrees C, were similar and, in both cases, binding was enthalpy-driven. The interactions of ADP, 2'deoxyADP, GDP, and IDP with the eukaryotic enzyme differed in enthalpic and entropic terms, whereas the Delta G degrees values obtained were similar due to enthalpy--entropy compensation. The binding of the enzyme to nonphysiological nucleotides, such as AMP--PNP, 3'deoxyADP, and 3'-deoxy-3'-amino-ADP, appears to differ in several respects. Crystallography of the protein bound to 3'-deoxy-3'-amino-ADP showed that the drug was in a distorted position, and was unable to interact correctly with active site side chains. The interaction of pyrimidine nucleoside diphosphates with the hexameric enzyme is characterized by a lower affinity than that with purine nucleotides. Titration showed the stoichiometry of the interaction to be abnormal, with 9--12 binding sites/hexamer. The presence of supplementary binding sites might have physiological implications.


  • Organizational Affiliation

    Istituto Pasteur Fondazione Cenci Bolognetti, Università di Roma La Sapienza, 5 P. le Aldo Moro, 00185 Roma, Italy.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
NUCLEOSIDE DIPHOSPHATE KINASE
A, B, C
155Dictyostelium discoideumMutation(s): 0 
EC: 2.7.4.6
UniProt
Find proteins for P22887 (Dictyostelium discoideum)
Explore P22887 
Go to UniProtKB:  P22887
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP22887
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
3AN PDBBind:  1HIY Kd: 8.30e+5 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.325 
  • R-Value Work: 0.220 
  • R-Value Observed: 0.220 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 71.62α = 90
b = 71.62β = 90
c = 153.8γ = 120
Software Package:
Software NamePurpose
X-PLORrefinement
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2001-05-31
    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: 2018-02-28
    Changes: Data collection
  • Version 1.4: 2019-05-08
    Changes: Data collection, Experimental preparation
  • Version 1.5: 2023-12-13
    Changes: Data collection, Database references, Other, Refinement description