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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/228510
Structure and mechanistic basis of NrdR, a bacterial master regulator of ribonucleotide reduction
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Ribonucleotide reductases (RNRs) are the essential enzymes responsible for synthesizing dNTPs, the building blocks of DNA. In bacteria, the entire RNR network is controlled by the master regulator NrdR. As a regulator of
an essential pathway with no eukaryotic equivalent, NrdR is a promising antimicrobial target. Recent structural studies have outlined a mechanism of action for NrdR, in which ATP and dATP induce changes in the protein
quaternary structure, regulating RNR repression. However, due to a lack of functional studies linking the known structures to their biological roles, the activation mechanism of NrdR is not yet fully understood.
Here, we conducted a comprehensive study of NrdR in Escherichia coli and Pseudomonas aeruginosa. We delimited the NrdR regulon, combining transcriptomics and motif-based sequence analysis. We crystallized E. coli
NrdR and identified the protein-protein interfaces involved in its oligomerization, including strong interactions between NrdR dimers to form tetramers, and less stable interfaces connecting such tetramers. We examined the variability of the quaternary structures of NrdR depending on the bound nucleotides by SEC-MALS and atomic force microscopy, and correlated structure to function using point mutations, EMSAs, and in vitro transcription
assays. Overall, our results demonstrate the mechanism used by NrdR to modulate its quaternary structure and activity, deciphering essential interactions between subunits, and paving the way for targeted antimicrobial
therapies.
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PEDRAZ LÓPEZ, Lucas, SZURA, Arkadiusz, SCHMITZ, Claus, RUBIO CANALEJAS, Alba, MARTÍNEZ MATEOS, Ángela, SANTELLA, Anthony, GOMILA LLUCH, Gabriel, CALÒ, Annalisa, SOLÀ, Maria, TORRENTS SERRA, Eduard. Structure and mechanistic basis of NrdR, a bacterial master regulator of ribonucleotide reduction. _International Journal of Biological Macromolecules_. 2026. [consulta: 8 de abril de 2026]. ISSN: 0141-8130. [Disponible a: https://hdl.handle.net/2445/228510]