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)

We report the isolation and sequencing of genomic clones encompassing the entire alpha-tubulin II gene from the human malaria parasite Plasmodium falciparum. This gene is closely related to, but significant different from the alpha-tubulin I gene that we have described previously. These two genes represent the entire complement of alpha-tubulin sequences in this organism and are expressed in a stage-specific manner. The alpha-II gene is present as a single copy and encodes a tubulin molecule with a predicted length of 450 amino acid residues (49.7 kDa). Like the alpha-I gene, it contains two introns, which are in identical positions to those of alpha-I, but are about one-third smaller. The deduced alpha-II protein is very similar to alpha-tubulin I (94.2% amino acid identity), except for notable differences across residues 40-45. In addition, unlike the great majority of alpha-tubulin genes (including alpha-I), alpha-II does not encode a terminal tyrosine residue. Using pulsed field gel electrophoresis we demonstrate that the two alpha-tubulin genes, together with the single beta-tubulin gene, are unlinked, all residing on different chromosomes. We assign alpha-I to chromosome 9, alpha-II to chromosome 4 and beta-tubulin to chromosome 10.
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PMID:The tubulin genes of the human malaria parasite Plasmodium falciparum, their chromosomal location and sequence analysis of the alpha-tubulin II gene. 209 Sep 47

Malaria parasites switch to sexual development after a period of vegetative growth in the host's erythrocytes. This switch, vital for parasite transmission to mosquitoes, is little understood at the genetic level. Likely candidates for developmental control are the alpha- and beta-tubulin subunits required for microtubule assembly. We report here that the transcription of the alpha- and beta-tubulin genes in Plasmodium falciparum show a radically different pattern of transcription in the sexual and sexual phases of parasite growth. Our studies lead to the conclusion that three transcripts of the beta-tubulin gene differ by sequences in their 5'- or 3'-untranslated regions.
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PMID:Expression of alpha and beta tubulin genes during the asexual and sexual blood stages of Plasmodium falciparum. 209 Sep 48

As a step towards identifying exploitable differences between host and parasite at the molecular level, we have isolated and sequenced genomic clones encompassing an entire alpha-tubulin gene (designated alpha-tubulin I) from the human malaria parasite, Plasmodium falciparum. The gene, which contains two introns, encodes a product with a predicted length of 453 amino acid residues (50.3 kD). The protein sequence shows a high degree of homology to other alpha-tubulins, particularly that of the coccidian parasite, Toxoplasma gondii (94%), whose gene carries introns in identical positions. Only one copy of the alpha-tubulin I gene itself was found, although a second gene designated alpha-II was also identified which is closely related but which differs at both the nucleotide and amino acid sequence levels. The alpha-I and beta-tubulin genes were found to reside on different chromosomes.
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PMID:Isolation of alpha-tubulin genes from the human malaria parasite, Plasmodium falciparum: sequence analysis of alpha-tubulin. 269 1

We describe the isolation and characterization of a gene for beta-tubulin from the malaria parasite, Plasmodium falciparum. This organism appears to contain a single gene encoding beta-tubulin. A single transcript from this gene can be detected in the total RNA of the parasite's asexual blood stages. The complete sequence for the gene has been elucidated. It has two introns, one of which has a position identical to that of a related parasite, Toxoplasma gondii. The gene shows the usual preference for codons with A or T in the third position. The predicted amino acid sequence is compared with that of T. gondii and the human host. Further comparisons between these and fungal sequences of beta-tubulins resistant to benomyl, a drug binding this protein, highlight differences that could be exploited in the development of parasite-specific antitubulin drugs.
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PMID:Cloning of a beta-tubulin gene from Plasmodium falciparum. 269 2

Microtubules are cytoskeletal polymers containing repeating alpha/beta-tubulin heterodimers and are found in all eukaryotes including the malaria parasite Plasmodium falciparum. Diverse cellular functions such as chromosomal segregation, organelle transport and the determination of cell shape and motility are all dependent on microtubules. This essential role played by tubulin in cells is reflected in the effective use of anti-microtubule agents as fungicides, herbicides, anti-parasitic and anti-cancer agents. Plasmodium falciparum microtubules have been proposed as a potential antimalarial drug target and knowledge of their molecular composition and cellular architecture in blood-stage parasites is required to substantiate this premise. We report here that: (i) the two alpha-tubulin isotypes, alphaI- and alphaII-tubulin, are produced in both asexual and sexual blood-stage parasites, contrary to the previous report that alphaII-tubulin was specific to male gametocytes; (ii) tubulin production is highly stage-dependent in asexual parasites, reaching its maximum level in schizonts and segmenters and (iii) there is evidence of post-translational polyglutamylation of tubulin. The glutamylation of P. falciparum tubulins is the first reported post-translational modification of tubulin in this organism and was found only in the microtubule-organising centres and post-mitotic microtubular structures, suggesting possible roles for this modification in spindle pole body formation and merozoite biogenesis. Taken together, these findings form the basis for a better biological appreciation of P. falciparum microtubules and for the correct deployment of purified tubulins in the evaluation of microtubule inhibitors as potential antimalarial drugs.
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PMID:Isotype expression, post-translational modification and stage-dependent production of tubulins in erythrocytic Plasmodium falciparum. 1797 43

Loop-mediated isothermal amplification (LAMP) is a novel method that rapidly amplifies target DNA with high specificity under isothermal conditions. It has been applied as a diagnostic tool for several infectious diseases, including viral, bacterial, and parasitic diseases. In the present study, we developed a LAMP method for the molecular diagnosis of Plasmodium knowlesi infection (PkLAMP) and evaluated its sensitivity, specificity, and clinical applicability. We designed three sets of PkLAMP primers for the species-specific beta-tubulin gene. The primer sets for PkLAMP specifically amplified the autologous DNA extracts of P. knowlesi, and the sensitivity of the test was 100-fold that of single-PCR assay. These results indicate that our PkLAMP method can be used to efficiently distinguish between P. knowlesi and other malaria parasites. To evaluate the feasibility of using in vivo materials, comparisons of PkLAMP and the conventional nested PCR (nPCR) method and microscopic examination were made with blood samples from two experimentally infected monkeys. These studies showed that P. knowlesi infection can be identified much earlier with PkLAMP than with nPCR and microscopy. Moreover, the detection performance of PkLAMP using whole blood as the template was identical to that of PkLAMP when genomic DNA extracts were used. These results suggest that the PkLAMP method is a promising tool for molecular diagnosis of P. knowlesi infection in areas of endemicity.
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PMID:Evaluation of a loop-mediated isothermal amplification method as a tool for diagnosis of infection by the zoonotic simian malaria parasite Plasmodium knowlesi. 2044 68