23S ribosomal RNA domain V (23S rRNA domain V)

Domain V of the 23S ribosomal RNA (rRNA) is a central component of the bacterial 50S ribosomal subunit and constitutes the core of the peptidyl transferase center (PTC) [1]. This region is essential for life as it catalyzes the formation of peptide bonds between amino acids during protein synthesis [2, 3]. Because of its critical role and high conservation across bacterial species, Domain V serves as the primary target for several major classes of antibiotics, including macrolides, lincosamides, oxazolidinones, and pleuromutilins [1, 4]. These drugs typically bind within the PTC or the adjacent nascent peptide exit tunnel (NPET), physically obstructing the growth of the protein chain or preventing the proper positioning of tRNA molecules [2]. Resistance to these antibiotics often arises through specific point mutations in the Domain V sequence or through the action of methyltransferase enzymes that modify key nucleotides, such as A2058, to prevent drug binding [4, 6]. Understanding the structural nuances of Domain V is vital for the development of next-generation antimicrobials capable of overcoming prevalent resistance mechanisms [1]. Furthermore, the high degree of similarity between bacterial 23S rRNA and human mitochondrial 16S rRNA can lead to off-target effects and toxicity in certain drug classes [4]. Clinical monitoring of mutations in this domain is a standard practice for determining antibiotic susceptibility in various pathogens [6].

Other names

Peptidyl transferase centerPTCDomain V of the 23S rRNA50S ribosomal subunit peptidyl transferase center

Inhibition of bacterial protein synthesis by binding to the peptidyl transferase center (PTC) or the nascent peptide exit tunnel (NPET) within the 50S subunit, which sterically hinders peptide bond formation or the elongation of the nascent polypeptide chain [1, 2].