Bacterial transcriptional repressor NrdR – a flexible multifactorial nucleotide sensor DOI Creative Commons
Inna Rozman Grinberg, Ornella Bimaï, Saher Shahid

et al.

FEBS Journal, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

NrdR is a bacterial transcriptional repressor consisting of zinc (Zn)‐ribbon domain followed by an ATP‐cone domain. Understanding its mechanism action could aid the design novel antibacterials. binds specifically to two “NrdR boxes” upstream ribonucleotide reductase operons, which Escherichia coli has three: nrdHIEF, nrdDG and nrdAB, in last we identified new box. We show that E. (EcoNrdR) similar binding strength all three sites when loaded with ATP plus deoxyadenosine triphosphate (dATP) or equivalent diphosphate combinations. No other combination adenine nucleotides promotes DNA. present crystal structures EcoNrdR–ATP–dATP EcoNrdR–ADP–dATP, are first high‐resolution NrdR. have also determined cryo‐electron microscopy DNA‐bound filaments EcoNrdR–ATP. Tetrameric forms EcoNrdR involve alternating interactions between pairs Zn‐ribbon domains ATP‐cones. The reveal considerable flexibility relative orientation ATP‐cones vs domains. structure shows significant conformational rearrangements Zn‐ribbons accompany DNA while retain same orientation. In contrast, ATP‐loaded sequester DNA‐binding residues such they unable bind Our results, previous structural biochemical study, point highly flexible that, correct nucleotides, adapt optimal promoter‐binding conformation.

Language: Английский

Bacterial transcriptional repressor NrdR – a flexible multifactorial nucleotide sensor DOI Creative Commons
Inna Rozman Grinberg, Ornella Bimaï, Saher Shahid

et al.

FEBS Journal, Journal Year: 2025, Volume and Issue: unknown

Published: March 3, 2025

NrdR is a bacterial transcriptional repressor consisting of zinc (Zn)‐ribbon domain followed by an ATP‐cone domain. Understanding its mechanism action could aid the design novel antibacterials. binds specifically to two “NrdR boxes” upstream ribonucleotide reductase operons, which Escherichia coli has three: nrdHIEF, nrdDG and nrdAB, in last we identified new box. We show that E. (EcoNrdR) similar binding strength all three sites when loaded with ATP plus deoxyadenosine triphosphate (dATP) or equivalent diphosphate combinations. No other combination adenine nucleotides promotes DNA. present crystal structures EcoNrdR–ATP–dATP EcoNrdR–ADP–dATP, are first high‐resolution NrdR. have also determined cryo‐electron microscopy DNA‐bound filaments EcoNrdR–ATP. Tetrameric forms EcoNrdR involve alternating interactions between pairs Zn‐ribbon domains ATP‐cones. The reveal considerable flexibility relative orientation ATP‐cones vs domains. structure shows significant conformational rearrangements Zn‐ribbons accompany DNA while retain same orientation. In contrast, ATP‐loaded sequester DNA‐binding residues such they unable bind Our results, previous structural biochemical study, point highly flexible that, correct nucleotides, adapt optimal promoter‐binding conformation.

Language: Английский

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