YcbX and yiiM, two novel determinants for resistance of Escherichia coli to N-hydroxylated base analogues

Stanislav G. Kozmin, Prune Leroy, Youri I Pavlov, Roel M. Schaaper

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49 Citations (Scopus)

Abstract

We have shown previously that lack of molybdenum cofactor (MoCo) in Escherichia coli leads to hypersensitivity to the mutagenic and toxic effects of N-hydroxylated base analogues, such as 6-N-hydroxylaminopurine (HAP). However, the nature of the MoCo-dependent mechanism is unknown, as inactivation of all known and putative E. coli molybdoenzymes does not produce any sensitivity. Presently, we report on the isolation and characterization of two novel HAP-hypersensitive mutants carrying defects in the ycbX or yiiM open reading frames. Genetic analysis suggests that the two genes operate within the MoCo-dependent pathway. In the absence of the ycbX- and yiiM-dependent pathways, biotin sulfoxide reductase plays also a role in the detoxification pathway. YcbX and YiiM are hypothetical members of the MOSC protein superfamily, which contain the C-terminal domain (MOSC) of the eukaryotic MoCo sulphurases. However, deletion of ycbX or yiiM did not affect the activity of human xanthine dehydrogenase expressed in E. coli, suggesting that the role of YcbX and YiiM proteins is not related to MoCo sulphuration. Instead, YcbX and YiiM may represent novel MoCo-dependent enzymatic activities. We also demonstrate that the MoCo/YcbX/YiiM-dependent detoxification of HAP proceeds by reduction to adenine.

Original languageEnglish (US)
Pages (from-to)51-65
Number of pages15
JournalMolecular Microbiology
Volume68
Issue number1
DOIs
StatePublished - Apr 1 2008

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Escherichia coli
Xanthine Dehydrogenase
Poisons
Adenine
molybdenum cofactor
Human Activities
Open Reading Frames
Hypersensitivity
Proteins
Genes

ASJC Scopus subject areas

  • Microbiology
  • Molecular Biology

Cite this

YcbX and yiiM, two novel determinants for resistance of Escherichia coli to N-hydroxylated base analogues. / Kozmin, Stanislav G.; Leroy, Prune; Pavlov, Youri I; Schaaper, Roel M.

In: Molecular Microbiology, Vol. 68, No. 1, 01.04.2008, p. 51-65.

Research output: Contribution to journalArticle

Kozmin, Stanislav G. ; Leroy, Prune ; Pavlov, Youri I ; Schaaper, Roel M. / YcbX and yiiM, two novel determinants for resistance of Escherichia coli to N-hydroxylated base analogues. In: Molecular Microbiology. 2008 ; Vol. 68, No. 1. pp. 51-65.
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