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 journalArticle

15 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 1 2011

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Adenosine Diphosphate Sugars
Adenosine Diphosphate Ribose
Guanine Nucleotides
Adenosine Monophosphate
Sugar Phosphates
Escherichia coli Proteins
DNA
Substrates
Catalysis
DNA Replication
Reaction products
Kinetic parameters
Escherichia coli
Binding Sites
Mutation
8-oxo-7,8-dihydrodeoxyguanosine diphosphate
human NUDT5 protein
Enzymes
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology

Cite this

Cleavage of oxidized guanine nucleotide and ADP sugar by human NUDT5 protein. / Ito, Riyoko; Sekiguchi, Mutsuo; Setoyama, Daiki; Nakatsu, Yoshimichi; Yamagata, Yuriko; Hayakawa, Hiroshi.

In: Journal of Biochemistry, Vol. 149, No. 6, 01.06.2011, p. 731-738.

Research output: Contribution to journalArticle

Ito, Riyoko ; Sekiguchi, Mutsuo ; Setoyama, Daiki ; Nakatsu, Yoshimichi ; Yamagata, Yuriko ; Hayakawa, Hiroshi. / Cleavage of oxidized guanine nucleotide and ADP sugar by human NUDT5 protein. In: Journal of Biochemistry. 2011 ; Vol. 149, No. 6. pp. 731-738.
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