Cloning, expression and characterisation of a human Nudix hydrolase specific for adenosine 5′-diphosphoribose (ADP-ribose)

Shengrong Lin, Lakhdar Gasmi, Yi Xie, Kang Ying, Shaohua Gu, Zhao Wang, Hua Jin, Yueqiong Chao, Chaoqun Wu, Zongxiang Zhou, Rong Tang, Yumin Mao, Alexander G. McLennan

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

The human NUDT9 gene has been mapped to 4q22 and shown to give rise to two alternatively spliced mRNAs, NUDT9α and NUDT9β, that encode a member of the Nudix hydrolase family. Both transcripts were readily detected in heart and skeletal muscle and also in liver, kidney and pancreas. NUDT9α protein was expressed in Escherichia coli and shown specifically to hydrolyse ADP-ribose and IDP-ribose to the corresponding nucleoside 5′-monophosphates and ribose 5-phosphate. No other nucleotide substrates were hydrolysed significantly. NUDT9α was inhibited by fluoride and by N-acetyl-p-benzoquinoneimine and had Km and kcat values of 180 μM and 8 s-1 respectively with ADP-ribose as substrate. The full-length 39.1 kDa NUDT9α has a potential mitochondrial leader sequence, which would give rise to a mature 34.2 kDa mitochondrial protein. Apart from the high Km value, the properties of NUDT9α are close to those of the known mammalian 40 kDa cytoplasmic ADPRibase-1 and 35 kDa mitochondrial ADPRibase-m. However, any relationship between the NUDT9 species and the previously reported ADPRibases remains to be established.

Original languageEnglish (US)
Pages (from-to)127-135
Number of pages9
JournalBiochimica et Biophysica Acta - Protein Structure and Molecular Enzymology
Volume1594
Issue number1
DOIs
StatePublished - Jan 31 2002

Keywords

  • ADP-ribose
  • NUDT9
  • Nucleotide metabolism
  • Nudix
  • Pyrophosphatase

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology

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