NUDT5 hydrolyzes oxidized deoxyribonucleoside diphosphates with broad substrate specificity

DNA Repair (Amst). 2009 Oct 2;8(10):1250-4. doi: 10.1016/j.dnarep.2009.07.011. Epub 2009 Aug 21.

Abstract

The human NUDT5 protein catalyzes the hydrolysis of 8-hydroxy-dGDP. To examine its substrate specificity, four oxidized deoxyribonucleotides (2-hydroxy-dADP, 8-hydroxy-dADP, 5-formyl-dUDP, and 5-hydroxy-dCDP) were incubated with the NUDT5 protein. Interestingly, all of the nucleotides, except for 5-hydroxy-dCDP, were hydrolyzed with various efficiencies. The kinetic parameters indicated that 8-hydroxy-dADP was hydrolyzed as efficiently as 8-hydroxy-dGDP. The hydrolyzing activities for their triphosphate counterparts were quite weak. These results suggest that the NUDT5 protein eliminates various oxidized deoxyribonucleoside diphosphates from the nucleotide pool and prevents their toxic effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Deoxyribonucleosides / chemistry
  • Deoxyribonucleosides / metabolism*
  • Diphosphates / chemistry*
  • Diphosphates / metabolism*
  • Humans
  • Hydrolysis
  • Kinetics
  • Oxidation-Reduction
  • Pyrophosphatases / metabolism*
  • Substrate Specificity

Substances

  • Deoxyribonucleosides
  • Diphosphates
  • NUDT5 protein, human
  • Pyrophosphatases