DNA polymerase III PolC subunit (Enterococcus faecium) (PolC)

The Enterococcus faecium DNA polymerase III PolC subunit is a fundamental enzyme required for the replication of the bacterial chromosome in Gram-positive bacteria. Unlike many other bacteria that rely on a single DnaE-type polymerase, Enterococcus faecium utilizes PolC as its primary replicative polymerase, which also contains an integrated 3'-5' exonuclease domain for high-fidelity proofreading (UniProt A0A9X4B319). This enzyme is essential for bacterial viability, making it a validated target for the development of novel antibacterial agents (Nature Communications, 2024, DOI: 10.1038/s41467-024-53944-w). Inhibitors such as ibezapolstat and ACX-801 function as guanine analogues that bind to the active site, competing with natural nucleotides and stalling DNA synthesis (Acurx Pharmaceuticals, 2024). Because PolC is structurally distinct from eukaryotic DNA polymerases, these inhibitors offer high selectivity and a reduced risk of host toxicity (Antibiotics, 2021, 10(6), 732). Targeting this subunit is a promising strategy for addressing multidrug-resistant infections, particularly those caused by vancomycin-resistant Enterococci (VRE) (Antimicrobial Agents and Chemotherapy, 1999, 43(8), 1982-1992). However, the emergence of resistance through specific mutations in the PolC binding pocket remains a significant therapeutic challenge (Nature Communications, 2024).

Other names

DNA polymerase III subunit alpha (PolC-type)polCDNA nucleotidyltransferaseDNA-directed DNA polymerase III PolC-type

Inhibition of DNA synthesis by competitively binding to the PolC active site as a guanine analogue and sequestering the enzyme in an inactive DNA-drug-protein complex.