DNA polymerase III subunit alpha (PolC) (PolC)

DNA polymerase III subunit alpha (PolC) is the primary enzyme responsible for chromosomal DNA replication in Gram-positive bacteria, including the opportunistic pathogen Enterococcus faecium [1][2]. It is a large, multi-domain protein that catalyzes the addition of deoxyribonucleotides to a growing DNA strand and possesses intrinsic 3'-5' exonuclease activity for high-fidelity proofreading [1][3]. In many Gram-positive species, PolC is the essential replicative polymerase, distinguishing it from the DnaE-type polymerases found in Gram-negative bacteria like Escherichia coli [2][4]. This structural divergence from both Gram-negative and eukaryotic polymerases makes PolC an attractive target for narrow-spectrum antibiotic development [4][5]. Small molecule inhibitors, such as 6-anilinouracils, have been shown to bind PolC and inhibit DNA synthesis, offering a potential therapeutic strategy against multi-drug resistant strains like vancomycin-resistant Enterococci (VRE) [4][5]. Targeting PolC disrupts the bacterial life cycle by preventing genome duplication, ultimately leading to cell death [2][5]. The enzyme's unique binding pocket for certain inhibitors allows for selectivity over human DNA polymerases, reducing potential host toxicity [4]. However, the clinical utility of PolC inhibitors faces challenges such as the potential for rapid emergence of resistance through single-site mutations in the polC gene [5].

Other names

DNA polymerase III PolC-typepolCDNA polymerase III catalytic subunitReplicative DNA polymerase PolCEnterococcus faecium DNA polymerase III PolC

Inhibition of DNA synthesis by binding to the PolC enzyme and competing with dGTP, thereby preventing nucleotide incorporation and halting DNA chain elongation.