Neisseria gonorrhoeae class Ia ribonucleotide reductase alpha subunit N-terminal cone domain (Ng NrdA cone domain)

The Neisseria gonorrhoeae class Ia ribonucleotide reductase (RNR) alpha subunit N-terminal cone domain is a critical allosteric regulatory site responsible for controlling the enzyme's activity (UniProt: Q5F9W7). RNR is the only enzyme capable of the de novo conversion of ribonucleotides into deoxyribonucleotides (dNTPs), making it an essential component for DNA replication and repair in the pathogen (PubMed: 16824030). The N-terminal cone domain, frequently referred to as the ATP-cone, acts as a molecular switch that binds ATP to activate the enzyme or dATP to inhibit it, ensuring balanced dNTP pools (PubMed: 21854613). Due to the global rise of multi-drug resistant Neisseria gonorrhoeae, this domain has become a focal point for the development of novel antibiotics that aim to starve the bacteria of DNA precursors (PubMed: 30305513). Targeting this specific domain offers a strategy to bypass existing resistance mechanisms to traditional antibiotics like cephalosporins. Current research focuses on identifying small molecules that can mimic the inhibitory state of the ATP-cone to achieve a bactericidal effect (PubMed: 26365771).

Other names

NrdA ATP-coneRibonucleoside-diphosphate reductase alpha subunit N-terminal domainNeisseria gonorrhoeae RNR alpha-subunit cone domainATP-cone domain of NrdA

Allosteric inhibition of ribonucleotide reductase activity by binding to the N-terminal regulatory site, preventing the conversion of ribonucleotides to deoxyribonucleotides and subsequently halting bacterial DNA replication and repair.