Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deoxyribonucleic acid (DNA) gyrase is an important enzyme that facilitates the movement of replication and transcription complexes through DNA by creating negative supercoils ahead of the complex. Its presence in Plasmodium falciparum is now established and considered a good drug target since it is absent in the human host. The sequence of P. falciparum gyrase A subunit was analyzed for its messenger ribonucleic acid (mRNA) folding as well as target accessibility for ribozymes. The four GUC triplet sites identified at 334, 491, 1907, and 2642 nucleotide positions of the Gyrase A mRNA were also accessible to oligos by RNase H assay. Site GUC491 was optimally accessible followed by GUC1907, GUC334, and GUC2642 sites. Ribozymes were produced against all these sites and tested for their in vitro transcript cleavage potentials where RZ491 showed the maximum cleavage rate. Therefore, this ribozyme (RZ491) was chemically synthesized albeit with modifications so as to make it resistant against ribonuclease attack. The modified ribozyme retained its cleavage potential and was able to inhibit the P. falciparum parasite growth up to 49.54% and 74.77% at 20 and 30 microM ribozyme concentrations, respectively, as compared to the untreated culture. However, up to 20% and 24.32% parasite growth inhibition was observed at the same ribozyme concentrations of 20 and 30 microM when compared with control ribozyme-treated cultures. This ribozyme as well as other targets identified here can be investigated further to develop the effective chemotherapeutic agents against malaria.
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PMID:Ribozyme cleavage of Plasmodium falciparum gyrase A gene transcript affects the parasite growth. 1852 2

The malaria parasite Plasmodium and other apicomplexans such as Toxoplasma evolved from photosynthetic organisms and contain an essential, remnant plastid termed the apicoplast. Transcription of the apicoplast genome is polycistronic with extensive RNA processing. Yet little is known about the mechanism of apicoplast RNA processing. In plants, chloroplast RNA processing is controlled by multiple pentatricopeptide repeat (PPR) proteins. Here, we identify the single apicoplast PPR protein, PPR1. We show that the protein is essential and that it binds to RNA motifs corresponding with previously characterized processing sites. Additionally, PPR1 shields RNA transcripts from ribonuclease degradation. This is the first characterization of a PPR protein from a nonphotosynthetic plastid.
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PMID:An essential pentatricopeptide repeat protein in the apicomplexan remnant chloroplast. 3145 37