Mycobacterial 50S ribosomal subunit (50S)

The mycobacterial 50S ribosomal subunit is the larger component of the 70S ribosome in mycobacteria, including the pathogen Mycobacterium tuberculosis [1, 14]. It is a complex ribonucleoprotein assembly composed of 23S ribosomal RNA (rRNA), 5S rRNA, and over 30 ribosomal proteins [8, 14]. The primary biological function of the 50S subunit is to catalyze peptide bond formation at the peptidyl transferase center (PTC) and to facilitate the passage of the growing polypeptide through the nascent polypeptide exit tunnel (NPET) [8, 17]. Because protein synthesis is essential for bacterial survival and replication, the 50S subunit serves as a major therapeutic target for several classes of antibiotics, such as macrolides, oxazolidinones, and lincosamides [1, 10, 16]. These drugs typically bind to the PTC or NPET, disrupting the elongation or initiation phases of translation [14, 17]. However, the structural similarity between the bacterial 50S subunit and the human mitochondrial ribosome can lead to significant clinical safety concerns, including myelosuppression and neuropathy, due to off-target inhibition of mitochondrial protein synthesis [10, 11, 21].

Other names

Large ribosomal subunit50S ribosome50S large ribosomal subunit

Drugs targeting the mycobacterial 50S ribosomal subunit primarily act by binding to the peptidyl transferase center (PTC) or the nascent polypeptide exit tunnel (NPET), thereby inhibiting peptide bond formation or blocking the exit of the growing polypeptide chain [1, 14, 17]. Oxazolidinones specifically prevent the formation of the 70S initiation complex by binding to the A-site of the PTC [10, 17]. Tuberactinomycins like capreomycin bind at the subunit interface, interacting with helix 69 of the 50S subunit to block translocation [7, 9].