DNA-directed RNA polymerase (RNAP) (RNAP)

The RNA polymerase active site is the catalytic center of the enzyme responsible for the synthesis of RNA from a DNA or RNA template [UniProt, 2024]. This site is characterized by a highly conserved structure that coordinates two divalent metal ions, usually magnesium, which are essential for the nucleophilic attack during phosphodiester bond formation [Nature, 2017]. In bacteria, the active site is the primary target for the rifamycin class of antibiotics, such as rifampicin, which bind within the DNA-RNA hybrid binding site to sterically block the elongation of the nascent RNA chain [StatPearls, 2023]. Similarly, viral RNA-dependent RNA polymerases (RdRp) are targeted by nucleoside analogs like remdesivir and sofosbuvir, which act as competitive inhibitors or chain terminators to halt viral replication [NIH, 2020]. While eukaryotic RNA polymerases are generally not the primary targets for antimicrobial therapy to avoid host toxicity, certain compounds like actinomycin D interact with the transcription complex to treat specific cancers [PubChem, 2024]. The development of resistance, often through point mutations in the genes encoding the active site subunits (e.g., rpoB in bacteria), remains a significant challenge in clinical practice [Microbiology Society, 2019].

Other names

RNA polymeraseRNA polymerase active siteRNA-directed RNA polymeraseRNA-dependent RNA polymeraseRdRpRNA nucleotidyltransferaseTranscriptase

Inhibition of RNA synthesis through steric blockade of the RNA exit channel, competitive inhibition of nucleotide binding, or induction of premature chain termination [StatPearls, 2023; NIH, 2020].