Target intelligence / Profile preview

Bacterial DNA polymerase (DNA pol)

Target
DNA pol
Molecular classification
Enzyme, DNA-directed DNA polymerase, Transferase
01

Overview

Bacterial DNA polymerases are essential enzymes responsible for synthesizing new DNA strands by catalyzing the addition of nucleotides to a template, a process vital for bacterial growth and division [4]. The primary replicative enzyme in most bacteria is DNA Polymerase III, a multi-subunit complex where the alpha subunit (encoded by dnaE in most bacteria or polC in some Gram-positives) performs the catalytic activity [1, 3]. Because these bacterial enzymes have distinct structural features and sequences compared to eukaryotic DNA polymerases, they serve as specialized targets for the development of novel antibiotics [3]. Drugs such as Griselimycin target the polymerase's sliding clamp (DnaN) to arrest replication, while others like anilinouracils specifically inhibit the catalytic core of Gram-positive polymerases [2, 3]. Targeting this enzyme is a critical strategy for addressing antibiotic-resistant pathogens, including Mycobacterium tuberculosis, by halting their ability to replicate their genome [2, 4].

Other names
DNA-directed DNA polymeraseDNA nucleotidyltransferasePol IIIDnaEPolCDNA replicase
02

Mechanism of action

Inhibition of DNA synthesis by competitive blocking of the dNTP binding site on the catalytic subunit (e.g., DnaE or PolC) or by disrupting the interaction with the DnaN sliding clamp, which prevents the elongation of the DNA strand [2, 3].

03

Biological functions

DNA replicationDNA repairProofreadingMaintenance of genome integrityCell proliferation
04

Disease associations

Bacterial infectionTuberculosisSepsisPneumonia
05

Safety considerations

Cross-reactivity with human nuclear or mitochondrial DNA polymerasesRapid development of antimicrobial resistance via target mutationsSelectivity issues between Gram-positive and Gram-negative variants
06

Interacting drugs

Griselimycin

4 more in the full profile.

07

Biomarkers

Bacterial DNA synthesis rateMinimum inhibitory concentration (MIC)Bacterial load reductionDnaE gene mutations

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