3BTY

Crystal structure of human ABH2 bound to dsDNA containing 1meA through cross-linking away from active site


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.35 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.225 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Crystal structures of DNA/RNA repair enzymes AlkB and ABH2 bound to dsDNA.

Yang, C.G.Yi, C.Duguid, E.M.Sullivan, C.T.Jian, X.Rice, P.A.He, C.

(2008) Nature 452: 961-965

  • DOI: https://doi.org/10.1038/nature06889
  • Primary Citation of Related Structures:  
    3BI3, 3BIE, 3BKZ, 3BTX, 3BTY, 3BTZ, 3BU0, 3BUC

  • PubMed Abstract: 

    Escherichia coli AlkB and its human homologues ABH2 and ABH3 repair DNA/RNA base lesions by using a direct oxidative dealkylation mechanism. ABH2 has the primary role of guarding mammalian genomes against 1-meA damage by repairing this lesion in double-stranded DNA (dsDNA), whereas AlkB and ABH3 preferentially repair single-stranded DNA (ssDNA) lesions and can repair damaged bases in RNA. Here we show the first crystal structures of AlkB-dsDNA and ABH2-dsDNA complexes, stabilized by a chemical cross-linking strategy. This study reveals that AlkB uses an unprecedented base-flipping mechanism to access the damaged base: it squeezes together the two bases flanking the flipped-out one to maintain the base stack, explaining the preference of AlkB for repairing ssDNA lesions over dsDNA ones. In addition, the first crystal structure of ABH2, presented here, provides a structural basis for designing inhibitors of this human DNA repair protein.


  • Organizational Affiliation

    Department of Chemistry, The University of Chicago, 929 East 57th Street, Chicago, Illinois 60637, USA.


Macromolecules

Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Alpha-ketoglutarate-dependent dioxygenase alkB homolog 2C [auth A]203Homo sapiensMutation(s): 4 
Gene Names: ALKBH2ABH2
EC: 1.14.11
UniProt & NIH Common Fund Data Resources
Find proteins for Q6NS38 (Homo sapiens)
Explore Q6NS38 
Go to UniProtKB:  Q6NS38
PHAROS:  Q6NS38
GTEx:  ENSG00000189046 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6NS38
Sequence Annotations
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  • Reference Sequence

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Entity ID: 1
MoleculeChains LengthOrganismImage
DNA (5'-D(*DCP*DTP*DGP*DTP*DAP*DTP*(MA7)P*DAP*DCP*DTP*DGP*DCP*DG)-3')A [auth B]13N/A
Sequence Annotations
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  • Reference Sequence

Find similar nucleic acids by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains LengthOrganismImage
DNA (5'-D(*DTP*DCP*DGP*DCP*DAP*DGP*DTP*DTP*DAP*DTP*DAP*DCP*DA)-3')B [auth C]13N/A
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
XL3
Query on XL3

Download Ideal Coordinates CCD File 
D [auth B]propane-1-thiol
C3 H8 S
SUVIGLJNEAMWEG-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.35 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.225 
  • Space Group: P 65 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 77.915α = 90
b = 77.915β = 90
c = 226.04γ = 120
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling
PHASESphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2008-04-22
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.2: 2021-10-20
    Changes: Database references, Derived calculations