Mechanism of Discrimination of 8-Oxoguanosine versus Guanosine by Escherichia coli Fpg

J Phys Chem B. 2017 Jun 15;121(23):5679-5687. doi: 10.1021/acs.jpcb.7b00205. Epub 2017 Jun 7.


The mutagenic 8-oxoguanosine monophosphate, the predominant product of DNA oxidation, is excised by formamidopyrimidine glycosylase (Fpg) in bacteria. The mechanism of recognition of 8-oxodG, which differs subtly from its normal counterpart, guanosine monophosphate (dG), by Escherichia coli Fpg remains elusive due to the lack of structural data of E. coli Fpg bound to 8-oxodG. Here, we present solution-state structure of 8-oxodG oligomer bound to E. coli E3Q Fpg using UV resonance Raman (UVRR) spectroscopy. The vibrational spectra report on the π-stacking and hydrogen bonding interactions established by 8-oxodG with E. coli E3Q Fpg. Furthermore, we report on the interactions of E. coli E3Q Fpg with the normal, undamaged nucleotide, dG. We show that E. coli Fpg recognizes 8-oxodG and dG through their C2-amino group but only 8-oxodG forms extensive contacts with E. coli Fpg. Our findings provide a basis for mechanism of lesion recognition by E. coli Fpg.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA-Formamidopyrimidine Glycosylase / chemistry
  • DNA-Formamidopyrimidine Glycosylase / isolation & purification
  • DNA-Formamidopyrimidine Glycosylase / metabolism*
  • Escherichia coli / enzymology*
  • Guanosine / analogs & derivatives*
  • Guanosine / chemistry
  • Guanosine / metabolism*
  • Spectrum Analysis, Raman


  • Guanosine
  • 8-hydroxyguanosine
  • DNA-Formamidopyrimidine Glycosylase