Bacterial 50S ribosomal subunit – 23S rRNA domain V (23S rRNA domain V)

The bacterial 50S ribosomal subunit – 23S rRNA domain V is a critical structural and functional region of the large ribosomal subunit, primarily housing the peptidyl transferase center (PTC) [1.2.1, 1.5.4]. This domain is responsible for catalyzing the formation of peptide bonds between amino acids during protein synthesis, making it essential for bacterial viability [1.1.1, 1.2.2]. Because of its central role in translation, it serves as the primary target for several major classes of antibiotics, including macrolides, lincosamides, and oxazolidinones [1.1.3, 1.4.2]. These drugs typically bind within the PTC or the adjacent nascent peptide exit tunnel to obstruct the growth of the polypeptide chain [1.1.1, 1.2.3]. Resistance often arises through specific point mutations (e.g., A2058G) or enzymatic methylation of nucleotides within this domain, which reduces drug affinity [1.1.4, 1.5.1]. While highly selective for bacterial ribosomes, some drugs targeting this site can exhibit toxicity by cross-reacting with human mitochondrial ribosomes, which share structural similarities [1.3.1, 1.4.3].

Other names

Peptidyl transferase centerPTC23S ribosomal RNA domain V23S rRNA V regionPeptidyl transferase loop

Antibiotics targeting this domain inhibit protein synthesis by binding to the peptidyl transferase center (PTC) or the nascent peptide exit tunnel (NPET) [1.1.1]. Macrolides and ketolides block the exit tunnel, causing premature dissociation of peptidyl-tRNA [1.2.3, 1.4.1]. Lincosamides, chloramphenicol, and pleuromutilins directly inhibit peptide bond formation by interfering with the positioning of aminoacyl-tRNA in the A-site or P-site [1.1.2, 1.4.2]. Oxazolidinones prevent the formation of the functional 70S initiation complex or inhibit the first peptide bond formation [1.3.1, 1.5.1].