Mycobacterium tuberculosis DNA-directed RNA polymerase (Mtb RNAP)

Mycobacterium tuberculosis DNA-directed RNA polymerase (Mtb RNAP) is the essential enzyme responsible for transcribing the bacterial genome into RNA, a critical step for protein synthesis and cellular viability [1]. The enzyme is a multi-subunit complex, typically composed of alpha, beta, beta-prime, and omega subunits, which associate with a sigma factor to initiate transcription [2]. The catalytic core requires magnesium ions (Mg²⁺) and a DNA template to function, forming a stable complex during the elongation phase [2]. This complex is the primary target for the rifamycin class of antibiotics, such as rifampicin, which are cornerstones of first-line tuberculosis treatment [3]. These drugs bind to the beta subunit (encoded by the rpoB gene) near the active site, physically obstructing the path of the growing RNA transcript [2, 3]. Resistance to these drugs frequently arises through mutations in the rpoB gene, which encodes the beta subunit, posing a significant challenge to global health [4]. Understanding the structural dynamics of the Mtb RNAP-DNA-Mg²⁺ complex is vital for developing next-generation inhibitors to combat drug-resistant strains of tuberculosis [2].

Other names

Mtb RNA polymeraseDNA-directed RNA polymeraseRNA polymeraserpoB/rpoC complexMtb RNAP-DNA complex

Inhibition of RNA synthesis by binding to the beta subunit of the RNA polymerase within the DNA-Mg²⁺ complex, thereby sterically blocking the elongation of the nascent RNA chain [2, 3].