Plasmodium apicoplast 50S ribosome (Apicoplast 50S)

The Plasmodium apicoplast 50S ribosome is the large subunit of the prokaryotic-like 70S ribosome located within the apicoplast, a non-photosynthetic plastid essential for the survival of malaria-causing parasites (McFadden, 2011; Sidhu et al., 2007). This organelle, derived from an ancient red algal endosymbiont, houses critical metabolic pathways such as isoprenoid biosynthesis, which are vital for the parasite's asexual blood stage (Yeh and DeRisi, 2011). The 50S subunit serves as a primary target for several classes of antibiotics, including macrolides like azithromycin and lincosamides like clindamycin (Dahl and Rosenthal, 2007). These drugs bind to the subunit, typically at the peptide exit tunnel or the peptidyl transferase center, thereby inhibiting protein translation (Sidhu et al., 2007). A hallmark of targeting the apicoplast ribosome is the "delayed death" phenomenon, where the initial generation of parasites remains viable but their progeny fail to survive, necessitating the use of these drugs in combination with faster-acting antimalarials (Dahl and Rosenthal, 2007; Kennedy et al., 2019). Resistance to these agents can emerge through specific mutations in apicoplast-encoded components, such as the 23S ribosomal RNA or the ribosomal protein L4 (Goodman et al., 2013; Sidhu et al., 2007). Understanding the structural and functional nuances of this ribosome is crucial for developing next-generation antimalarials that can overcome existing resistance mechanisms (Gupta et al., 2014).

Other names

Apicoplast large ribosomal subunitApicoplast 50S subunitLSU of apicoplast ribosomePlasmodium falciparum apicoplast 50S ribosome

Inhibition of protein synthesis by binding to the 50S ribosomal subunit, specifically at the peptide exit tunnel or peptidyl transferase center, to block transpeptidation and peptide elongation (Sidhu et al., 2007; Dahl and Rosenthal, 2007).