biostudies-literatureRozman Grinberg IWenner-Gren StiftelsernaVetenskapsrådetCarl Tryggers Stiftelse för Vetenskaplig ForskningCancerfonden3091-3112https://www.ebi.ac.uk/biostudies/studies/S-EPMC12176259biostudies-literatureUnknown292(12)NrdR is a bacterial transcriptional repressor consisting of a zinc (Zn)-ribbon domain followed by an ATP-cone domain. Understanding its mechanism of action could aid the design of novel antibacterials. NrdR binds specifically to two "NrdR boxes" upstream of ribonucleotide reductase operons, of which Escherichia coli has three: nrdHIEF, nrdDG and nrdAB, in the last of which we identified a new box. We show that E. coli NrdR (EcoNrdR) has similar binding strength to all three sites when loaded with ATP plus deoxyadenosine triphosphate (dATP) or equivalent diphosphate combinations. No other combination of adenine nucleotides promotes binding to DNA. We present crystal structures of EcoNrdR-ATP-dATP and EcoNrdR-ADP-dATP, which are the first high-resolution crystal structures of an NrdR. We havThe FEBS journalBacterial transcriptional repressor NrdR - a flexible multifactorial nucleotide sensor.PMC121762592019-014002023-050742016-04855CTS 20:3612022-0368120 1287 PjF20 1210 PjFShahid SMartinez-Carranza MSjoberg BMLundin DStenmark PBanerjee ILogan DTBimai OPhilipp LRozman Grinberg IfalseBacterial transcriptional repressor NrdR - a flexible multifactorial nucleotide sensor.NrdR is a bacterial transcriptional repressor consisting of a zinc (Zn)-ribbon domain followed by an ATP-cone domain. Understanding its mechanism of action could aid the design of novel antibacterials. NrdR binds specifically to two "NrdR boxes" upstream of ribonucleotide reductase operons, of which Escherichia coli has three: nrdHIEF, nrdDG and nrdAB, in the last of which we identified a new box. We show that E. coli NrdR (EcoNrdR) has similar binding strength to all three sites when loaded with ATP plus deoxyadenosine triphosphate (dATP) or equivalent diphosphate combinations. No other combination of adenine nucleotides promotes binding to DNA. We present crystal structures of EcoNrdR-ATP-dATP and EcoNrdR-ADP-dATP, which are the first high-resolution crystal structures of an NrdR. We hav2025-01-01T00:00:00Z2025 Jun2026-06-03T07:55:19.593Z2026-04-26T03:10:41.112ZS-EPMC121762594002902210.1111/febs.70037