Multiple enzyme activities of Escherichia coli MutT protein for sanitization of DNA and RNA precursor pools

Biochemistry. 2005 May 3;44(17):6670-4. doi: 10.1021/bi047550k.


8-OxoGua (8-oxo-7,8-dihydroguanine) is produced in nucleic acids as well as in nucleotide pools of cells, by reactive oxygen species normally formed during cellular metabolic processes. MutT protein of Escherichia coli specifically degrades 8-oxoGua-containing deoxyribo- and ribonucleoside triphosphates to corresponding nucleoside monophosphates, thereby preventing misincorporation of 8-oxoGua into DNA and RNA, which would cause mutation and phenotypic suppression, respectively. Here, we report that the MutT protein has additional activities for cleaning up the nucleotide pools to ensure accurate DNA replication and transcription. It hydrolyzes 8-oxo-dGDP to 8-oxo-dGMP with a K(m) of 0.058 microM, a value considerably lower than that for its normal counterpart, dGDP (170 microM). Furthermore, the MutT possesses an activity to degrade 8-oxo-GDP to the related nucleoside monophosphate, with a K(m) value 8000 times lower than that for GDP. These multiple enzyme activities of the MutT protein would facilitate the high fidelity of DNA and RNA syntheses.

MeSH terms

  • DNA Replication*
  • DNA, Bacterial / biosynthesis
  • DNA, Bacterial / chemistry
  • DNA, Bacterial / metabolism*
  • Deoxyadenine Nucleotides / metabolism
  • Deoxycytosine Nucleotides / metabolism
  • Deoxyguanine Nucleotides / metabolism
  • Escherichia coli Proteins / metabolism*
  • Guanine / analogs & derivatives*
  • Guanine / metabolism*
  • Guanosine Triphosphate / analogs & derivatives*
  • Guanosine Triphosphate / metabolism
  • Hydrolysis
  • Kinetics
  • Multienzyme Complexes / metabolism*
  • Phosphoric Monoester Hydrolases / metabolism*
  • Pyrophosphatases
  • RNA, Bacterial / biosynthesis
  • RNA, Bacterial / chemistry
  • RNA, Bacterial / metabolism*
  • Thymine Nucleotides / metabolism
  • Transcription, Genetic


  • 8-oxo-7,8-dihydrodeoxyguanosine diphosphate
  • DNA, Bacterial
  • Deoxyadenine Nucleotides
  • Deoxycytosine Nucleotides
  • Deoxyguanine Nucleotides
  • Escherichia coli Proteins
  • Multienzyme Complexes
  • RNA, Bacterial
  • Thymine Nucleotides
  • 8-oxodeoxyguanosine triphosphate
  • 2'-deoxycytidine 5'-triphosphate
  • 8-hydroxyguanosine triphosphate
  • 8-hydroxyguanine
  • Guanine
  • Guanosine Triphosphate
  • deoxyguanosine triphosphate
  • Phosphoric Monoester Hydrolases
  • Pyrophosphatases
  • mutT protein, E coli
  • 2'-deoxyadenosine triphosphate
  • thymidine 5'-triphosphate