Cleavage of oxidized guanine nucleotide and ADP sugar by human NUDT5 protein

Riyoko Ito, Mutsuo Sekiguchi, Daiki Setoyama, Yoshimichi Nakatsu, Yuriko Yamagata, Hiroshi Hayakawa

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

MutT-related proteins, including Escherichia coli MutT and the human MTH1 (NUDT1), degrade 8-oxo-7, 8-dihydrodeoxyguanosine triphosphate (8-oxo-dGTP) to 8-oxo-dGMP and thereby prevent mutations caused by the misincorporation of 8-oxoguanine into DNA. The human NUDT5, which has an intrinsic activity to cleave ADP sugars to AMP and sugar phosphate, possesses the ability to degrade 8-oxo-dGDP to the monophosphate. Since 8-oxo-dGDP and 8-oxo-dGTP are interconvertible by cellular enzymes, NUDT5 has the potential to prevent errors during DNA replication. The two activities associated with NUDT5 exhibit different pH dependencies; the optimum for the cleavage of ADP ribose is pH 7-9, while that for 8-oxo-dGDPase is around pH 10. The kinetic parameters for the two types of reactions indicated that ADP ribose is a better substrate for NUDT5 compared with oxidized guanine nucleotides. The 8-oxo-dGDP cleavage was competitively inhibited by ADP ribose and its reaction product, AMP, and in reverse, the cleavage of ADP ribose was inhibited by 8-oxo-dGDP. These results imply that the two types of substrates may share the same binding site for catalysis.

Original languageEnglish
Pages (from-to)731-738
Number of pages8
JournalJournal of biochemistry
Volume149
Issue number6
DOIs
Publication statusPublished - Jun 2011

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Fingerprint Dive into the research topics of 'Cleavage of oxidized guanine nucleotide and ADP sugar by human NUDT5 protein'. Together they form a unique fingerprint.

Cite this