Mycobacterium tuberculosis 50S ribosomal subunit peptidyl-tRNA site (Mtb 50S P-site)

The Mycobacterium tuberculosis 50S ribosomal subunit P-site (peptidyl-tRNA site) is a fundamental component of the bacterial translation machinery, responsible for holding the tRNA molecule linked to the growing polypeptide chain (Belousoff et al., 2017). Located within the peptidyl transferase center (PTC) of the 50S subunit, this site is primarily composed of highly conserved segments of the 23S ribosomal RNA. It serves as a critical target for the oxazolidinone class of antibiotics, including linezolid and tedizolid, which are essential for the treatment of multidrug-resistant tuberculosis (MDR-TB) (Wilson, 2014). These drugs bind to the P-site and the adjacent A-site, sterically hindering the formation of the 70S initiation complex and the subsequent elongation steps of protein synthesis (Richter et al., 2007). While the target is specific to bacteria, structural similarities between the bacterial P-site and human mitochondrial ribosomes can lead to clinical toxicities such as myelosuppression and neuropathy during prolonged therapy (StatPearls, 2023). Resistance to drugs targeting this site typically arises through point mutations in the 23S rRNA or associated ribosomal proteins like L3, which alter the binding pocket and reduce drug affinity (PubMed, 2021).

Other names

M. tuberculosis 50S P-sitePeptidyl-tRNA binding site50S ribosomal P-siteMycobacterium tuberculosis 50S peptidyl siteMtb 50S PTC P-site

Inhibition of protein synthesis by binding to the 23S rRNA of the 50S subunit, which prevents the proper positioning of aminoacyl-tRNA and inhibits the formation of the 70S initiation complex or the translocation of peptidyl-tRNA (Wilson, 2014; Belousoff et al., 2017).