New insights into how bacteria control DNA synthesis open the door to next generation antimicrobials

Ribonucleotide reductases (RNR) are indispensable enzymes that convert ribonucleotides to deoxyribonucleotides (dNTPs), the precursors to make up DNA. Because DNA synthesis is fundamental to cell survival, RNR activity must be tightly controlled. In bacteria, this control is exerted by a specialized transcriptional regulator, NrdR, which has no equivalent in eukaryotic organisms and therefore represents a potential selective target for antimicrobial development. Despite its central role, the structural basis of NrdR's function and the mechanisms by which it senses cellular nucleotide levels and modulates RNR expression have remained only partially understood.