nrdAB

NrdAB refers to the class I ribonucleotide reductase (RNR) composed of two subunits, NrdA (the large catalytic subunit) and NrdB (the small metallocofactor-containing subunit). This enzyme catalyzes the reduction of ribonucleotides to deoxyribonucleotides, providing the building blocks required for DNA synthesis and repair. In bacteria, the NrdAB system is among the most widely studied forms of ribonucleotide reductase and is essential under aerobic conditions.

Structure and function: The holoenzyme typically forms a heterotetrameric complex consisting of two NrdA and two NrdB subunits. NrdA contains the catalytic site and the allosteric sites that regulate activity and substrate specificity. NrdB harbors a metal center and a stable tyrosyl radical that initiates catalysis. The catalytic radical is transferred through a redox chain from NrdB to a cysteine pair in NrdA, enabling the reduction of ribonucleotides to deoxyribonucleotides. Reducing equivalents are supplied by cellular systems such as thioredoxin or glutaredoxin.

Regulation and expression: RNR activity is controlled allosterically by ATP or dATP at the activity site, and by substrate binding at the specificity site to determine which NDP is reduced. Expression of the nrdAB operon is responsive to iron availability, oxidative stress, and DNA damage, aligning dNTP production with cellular needs.

Genetics and context: In many bacteria, nrdA and nrdB are co-transcribed as nrdAB. Class Ia NrdAB is the best-characterized form, but related systems (such as class Ib, with NrdEF and maturation factors) exist in other organisms. NrdAB is a notable target in antimicrobial research, and inhibitors like hydroxyurea act by disrupting the radical-based mechanism.