Nuclear magnetic resonance structural studies and molecular modeling of duplex DNA containing normal and 4'-oxidized abasic sites

Biochemistry. 2007 Mar 20;46(11):3096-107. doi: 10.1021/bi6024269. Epub 2007 Feb 27.


A 4'-oxidized abasic site (X) has been synthesized in a defined duplex DNA sequence, 5'-d(CCAAAGXACCGGG)-3'/3'-d(GGTTTCATGGCCC)-5' (1). Its structure has been determined by two-dimensional NMR methods, molecular modeling, and molecular dynamics simulations. 1 is globally B-form with the base (A) opposite X intrahelical and well-stacked. Only the alpha anomer of X is observed, and the abasic site deoxyribose is largely intrahelical. These results are compared with a normal abasic site (Y) in the same sequence context (2). Y is composed of a 60:40 mixture of alpha and beta anomers (2alpha and 2beta). In both 2alpha and 2beta, the base (A) opposite Y is intrahelical and well-stacked and the abasic site deoxyribose is predominantly extrahelical, consistent with the reported structures of the normal abasic site in a similar sequence context [Hoehn, S. T., Turner, C. J., and Stubbe, J. (2001) Nucleic Acids Res. 29, 3413-3423]. Molecular dynamics simulations reveal that the normal abasic site appears to be conformationally more flexible than the 4'-oxidized abasic site. The importance of the structure and flexibility of the abasic site in the recognition by the DNA repair enzyme Ape1 is discussed.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / chemistry*
  • DNA Damage / drug effects*
  • DNA-(Apurinic or Apyrimidinic Site) Lyase / metabolism
  • Electron Spin Resonance Spectroscopy
  • Models, Molecular
  • Nuclear Magnetic Resonance, Biomolecular
  • Nucleic Acid Conformation
  • Oligodeoxyribonucleotides / chemistry
  • Oxidation-Reduction


  • Oligodeoxyribonucleotides
  • DNA
  • DNA-(Apurinic or Apyrimidinic Site) Lyase

Associated data

  • PDB/2HOU
  • PDB/2HPX
  • PDB/2HSK
  • PDB/2HSL
  • PDB/2HSR
  • PDB/2HSS