Bacterial DNA-directed RNA polymerase subunit beta (RpoB) (RpoB)

The bacterial DNA-directed RNA polymerase (RNAP) beta subunit is a core catalytic component of the enzyme responsible for synthesizing RNA from a DNA template. A central feature of this subunit is its contribution to the DNA/RNA channel (also known as the main channel), which houses the DNA template and the nascent RNA-DNA hybrid during transcription elongation (UniProt Consortium, 2023). This channel is a vital therapeutic target because its occlusion or the stabilization of its mobile elements can halt the transcription process entirely. Rifamycins, the most prominent class of drugs targeting this subunit, bind near the active site within the RNA exit path, effectively acting as a "plug" that prevents the RNA transcript from extending beyond a few nucleotides (Campbell et al., 2001). Newer inhibitors like salinamides specifically target the DNA/RNA channel to interfere with the enzyme's translocation along the DNA (Degen et al., 2014). Targeting this site provides high selectivity for bacterial pathogens over human cells due to structural divergence in the polymerase subunits (Villain-Guillot et al., 2007). Resistance to these drugs is a major clinical concern and usually arises from mutations in the rpoB gene that modify the architecture of the channel or binding pocket (Goldstein, 2014).

Other names

RNA polymerase beta subunitDNA-directed RNA polymerase subunit betaRNAP beta subunitrpoBBacterial RNA polymerase beta subunit

Inhibition of bacterial transcription by binding to the beta subunit and sterically blocking the RNA exit channel or the DNA/RNA main channel, thereby preventing RNA chain elongation (Campbell et al., 2001; Degen et al., 2014).