Thiostrepton binds to malarial plastid rRNA

Abstract

Binding of the thiazolyl peptide antibiotic thiostrepton to the GTPase domain of 23S rRNA involves a few crucial nucleotides, notably A1067 (E. coif). Small RNA transcripts were prepared corresponding to the GTPase domain of the plastid 23S rRNA and the two forms of cytosolic 28S rRNAs found in the human malaria parasite Plasmodium falcipamm, as well as the plastid form of rRNA of the AIDS-related pathogen Toxoplasma gondii. Binding affinities of the wild type and mutated RNA sequences were as predicted; the malarial plastid sequence had by far the highest affinity, whereas that from toxoplasma did not bind thiostrepton.

Inhibition of mitochondrial and plastid activity of Plasmodium falciparum by minocycline

“…Thiostrepton binds to malarial plastid rRNA, but not to the mitochondria and cytoplasmic rRNA [24]. It impaired plastid protein synthesis, resulting in inhibition of the transcription of the rpoB/C gene [18].…”

Annotation transfer by homology among closely related genomes helps to identify protein function in Plasmodium species

“…The ribonucleic constituents are also considered as novel candidates for drug target of antimalarial drugs. Therefore, the new ribosomal proteins identified in this study can be potential candidates for malaria (Bottger, 2007;Clough et al, 1997;Rogers et al, 1997;Camps et al, 2002;Kiatfuengfoo et al, 1989;Yassin and Mankin, 2007;Sidhu et al, 2007). The transporter proteins in Plasmodium are yet to be exploited as drug targets and needs to be more investigated by the scientific community (Jana and Paliwal, 2007).…”

Annotation transfer by homology among closely related genomes helps to identify protein function in Plasmodium species

“…There 25 proteins involved in membrane transport and their role as drug targets and drug resistance is discussed elsewhere (Martin et al, 2009). There are 23 ribosomal proteins that are identified which also form the attractive category of drug targets (Bottger, 2007;Clough et al, 1997;Rogers et al, 1997;Camps et al, 2002;Kiatfuengfoo et al, 1989;Yassin and Mankin, 2007;Sidhu et al, 2007). The SPATR protein (XP_001349632.1) 1 which contains an altered thrombospondin type I repeat domain is found expressed at several stages of the parasitic life cycle.…”