2C53

A comparative study of uracil DNA glycosylases from human and herpes simplex virus type 1


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.216 
  • R-Value Work: 0.164 
  • R-Value Observed: 0.164 

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Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

A Comparative Study of Uracil-DNA Glycosylases from Human and Herpes Simplex Virus Type 1.

Krusong, K.Carpenter, E.P.Bellamy, S.R.W.Savva, R.Baldwin, G.S.

(2006) J Biol Chem 281: 4983

  • DOI: https://doi.org/10.1074/jbc.M509137200
  • Primary Citation of Related Structures:  
    2C53, 2C56

  • PubMed Abstract: 

    Uracil-DNA glycosylase (UNG) is the key enzyme responsible for initiation of base excision repair. We have used both kinetic and binding assays for comparative analysis of UNG enzymes from humans and herpes simplex virus type 1 (HSV-1). Steady-state fluorescence assays showed that hUNG has a much higher specificity constant (k(cat)/K(m)) compared with the viral enzyme due to a lower K(m). The binding of UNG to DNA was also studied using a catalytically inactive mutant of UNG and non-cleavable substrate analogs (2'-deoxypseudouridine and 2'-alpha-fluoro-2'-deoxyuridine). Equilibrium DNA binding revealed that both human and HSV-1 UNG enzymes bind to abasic DNA and both substrate analogs more weakly than to uracil-containing DNA. Structure determination of HSV-1 D88N/H210N UNG in complex with uracil revealed detailed information on substrate binding. Together, these results suggest that a significant proportion of the binding energy is provided by specific interactions with the target uracil. The kinetic parameters for human UNG indicate that it is likely to have activity against both U.A and U.G mismatches in vivo. Weak binding to abasic DNA also suggests that UNG activity is unlikely to be coupled to the subsequent common steps of base excision repair.


  • Organizational Affiliation

    Division of Molecular Biosciences, Imperial College London, South Kensington, London, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
URACIL DNA GLYCOSYLASE244Human alphaherpesvirus 1Mutation(s): 2 
EC: 3.2.2.3
UniProt
Find proteins for P10186 (Human herpesvirus 1 (strain 17))
Explore P10186 
Go to UniProtKB:  P10186
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP10186
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.80 Å
  • R-Value Free: 0.216 
  • R-Value Work: 0.164 
  • R-Value Observed: 0.164 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 42.406α = 90
b = 61.161β = 93.15
c = 43.62γ = 90
Software Package:
Software NamePurpose
CNSrefinement
MOLREPphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-11-28
    Type: Initial release
  • Version 1.1: 2015-04-01
    Changes: Derived calculations, Non-polymer description, Other, Structure summary, Version format compliance
  • Version 1.2: 2019-05-22
    Changes: Data collection, Other, Refinement description