Neisseria gonorrhoeae class Ia ribonucleotide reductase (RNR)

Neisseria gonorrhoeae class Ia ribonucleotide reductase (RNR) is an essential bacterial enzyme that catalyzes the rate-limiting step in the de novo synthesis of deoxyribonucleotides (dNTPs), the fundamental building blocks for DNA replication and repair (Narasimhan et al., 2022, eLife). The enzyme is a heterotetramer consisting of two large alpha subunits (NrdA) and two small beta subunits (NrdB), where the beta subunit contains a stable tyrosyl radical and a di-iron center necessary for catalysis (UniProtKB P0A0V2, P0A0V5). Because N. gonorrhoeae lacks alternative RNR classes (such as class II or III) found in many other bacteria, it is uniquely dependent on this class Ia enzyme for survival, making it a highly specific and attractive therapeutic target (Drug Discovery News, 2022). Recent research has identified novel small-molecule inhibitors, such as PTC-847 and PTC-672, which selectively target the gonococcal RNR over human isoforms (Narasimhan et al., 2022, eLife). These inhibitors function by promoting the formation of an inactive, ring-shaped alpha4beta4 quaternary structure, thereby halting DNA synthesis and effectively treating multidrug-resistant (MDR) gonorrhea in preclinical models (MIT News, 2022). This target is particularly significant given the global rise of "super-gonorrhea" strains that are resistant to current first-line antibiotics like ceftriaxone (WHO, 2025).

Other names

Ribonucleoside-diphosphate reductaseNrdA/NrdB complexNg RNRRibonucleotide reductase

Allosteric inhibition of the conversion of ribonucleotides to deoxyribonucleotides by promoting the formation of an inactive quaternary state (alpha4beta4 ring structure) (Narasimhan et al., 2022, eLife).