A study published in the International Journal of Biological Macromolecules presents the most detailed image obtained to date of NrdR, the main regulator of ribonucleotide reductases (RNR) in bacteria. The paper presents the first detailed images of the full structure of the NrdR protein and reveals how changes in its conformation and association affect the way it controls key processes within the cell. This study provides a conceptual and experimental basis for identifying new antibacterial targets and driving future therapeutic innovation.
The study was led by the Bacterial Infections: Antimicrobial Therapies research group at the Institute for Bioengineering of Catalonia (IBEC), headed by Professor Eduard Torrents from the Department of Genetics, Microbiology and Statistics at the Faculty of Biology of the University of Barcelona, and by the Mitochondrial Macromolecular Structural Biology research group at the Molecular Biology Institute of Barcelona (IBMB-CSIC), led by researcher Maria Solà. The paper, whose first co-author is Lucas Pedraz, involved the participation of IBEC's Nano-scale Bioelectrical Characterization research group.
Ribonucleotide reductases (RNRs) are the enzymes responsible for converting ribonucleotide molecules into deoxyribonucleotides (dNTPs), the precursors that make up DNA. This study now combines structural biology, biophysical characterization and functional assays to describe how the quaternary structure of NrdR responds to different nucleotide states and how these changes affect its regulatory activity. The research focuses on two major bacterial pathogens: Escherichia coli, a key model organism for studying fundamental bacterial physiology, and Pseudomonas aeruginosa, an opportunistic pathogen known for its inherent resistance to many antibiotics and its role in chronic infections.
"Targeting such an important regulator could weaken pathogenic bacteria or help restore their susceptibility to existing antibiotics, representing a promising avenue to counteract the growing problem of antimicrobial resistance," explains Eduard Torrents, ICREA Academia researcher.
