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  • 1
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: The elongation step of protein synthesis involves binding of aminoacyl-tRNA to the ribosomal A site, formation of a peptide bond and translocation of the newly formed peptidyl-tRNA to the P site. The nucleotide exchange factor EF-1β plays a major role in the regulation of this process by regenerating a GTP-bound EF-1α necessary for each elongation cycle. EF-1β has been shown to be phosphorylated and its phosphorylation is critical for optimal activity. We have previously identified a serine/threonine protein phosphatase 2C (PP2C) from the human malaria parasite Plasmodium falciparum. In the current work, we performed Far-Western analysis to identify PfPP2C substrates. Several components of the translation and transcription machinery were identified, including translation elongation factor 1-beta (PfEF-1β). PfEF-1β is efficiently phosphorylated by protein kinase C and this phosphorylation results in a 400% increase in its nucleotide exchange activity. PKC-phosphorylated PfEF-1β is readily and selectively dephosphorylated by recombinant and native PfPP2C, which downregulates the nucleotide exchange activity to its basal level. The identification of a translation elongation component as substrate for PP2C suggests an important regulatory function for this enzyme and suggests that it may be a good target for drug design in the fight against malaria.
    Type of Medium: Electronic Resource
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  • 2
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    Annual Review of Biochemistry 71 (2002), S. 275-305 
    ISSN: 0066-4154
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Chemistry and Pharmacology , Biology
    Notes: Abstract Proteases from a variety of protozoan parasites have been characterized at the molecular and cellular levels, and the many roles that proteases play in these organisms are coming into focus. Central roles have been proposed for proteases in diverse processes such as host cell invasion and egress, encystation, excystation, catabolism of host proteins, differentiation, cell cycle progression, cytoadherence, and both stimulation and evasion of host immune responses. Detailed structural and functional characterization of parasite proteases has led to novel insights into the workings of these fascinating catalytic machines. The possibility of developing selective inhibitors of key proteases of pathogenic parasites into novel chemotherapeutic strategies is being vigorously explored.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1365-2958
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Biology , Medicine
    Notes: Plasmodium falciparum is a protozoan parasite responsible for the most severe forms of human malaria. All the clinical symptoms and pathological changes seen during human infection are caused by the asexual blood stages of Plasmodium. Within host red blood cells, the parasite undergoes enormous developmental changes during its maturation. In order to analyse the expression of genes during intraerythrocytic development, DNA microarrays were constructed and probed with stage-specific cDNA. Developmental upregulation of specific mRNAs was found to cluster into functional groups and revealed a co-ordinated programme of gene expression. Those involved in protein synthesis (ribosomal proteins, translation factors) peaked early in development, followed by those involved in metabolism, most dramatically glycolysis genes. Adhesion/invasion genes were turned on later in the maturation process. At the end of intraerythrocytic development (late schizogony), there was a general shut-off of gene expression, although a small set of genes, including a number of protein kinases, were turned on at this stage. Nearly all genes showed some regulation over the course of development. A handful of genes remained constant and should be useful for normalizing mRNA levels between stages. These data will facilitate functional analysis of the P. falciparum genome and will help to identify genes with a critical role in parasite progression and multiplication in the human host.
    Type of Medium: Electronic Resource
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  • 4
    ISSN: 1476-4687
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics
    Notes: [Auszug] The parasitic nematode Ascaris lumbricoides infects one billion people worldwide. Its perienteric fluid contains an octameric haemoglobin that binds oxygen nearly 25,000 times more tightly than does human haemoglobin. Despite numerous investigations, the biological function of this ...
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  • 5
    ISSN: 1432-1432
    Keywords: Alleles ; Evolution ; Gene conversion ; Introns ; Nematode
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Abstract Globin genes from theCaenorhabditis speciesbriggsae andremanei were identified and compared with a previously describedC. elegans globin gene. The encoded globins share between 86% and 93% amino acid identity, with most of the changes in or just before the putative B helix.C. remanei was found to have two globin alleles,Crg1-1 andCrgl-2. The coding sequence for each is interrupted by a single intron in the same position. The exons of the two genes are only 1 % divergent at the nucleotide level and encode identical polypeptides. In contrast, intron sequence divergence is 16% and numerous insertions and deletions have significantly altered the size and content of both introns. Genetic crosses show thatCrg1-1 andCrgl-2 segregate as alleles. Homozygous lines for each allele were constructed and northern analysis confirmed the expression of both alleles. These data reveal an unusual situation wherein two alleles encoding identical proteins have diverged much more rapidly in their introns than the silent sites of their coding sequences, suggesting multiple gene conversion events.
    Type of Medium: Electronic Resource
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  • 6
    Electronic Resource
    Electronic Resource
    New York, NY : Wiley-Blackwell
    BioEssays 17 (1995), S. 177-182 
    ISSN: 0265-9247
    Keywords: Life and Medical Sciences ; Cell & Developmental Biology
    Source: Wiley InterScience Backfile Collection 1832-2000
    Topics: Biology , Medicine
    Notes: The parasitic nematode Ascaris lives in the low-oxygen intestinal folds of over one billion people world-wwide. The worm has an octameric hemoglobin that binds oxygen four orders of magnitude more tightly than does human hemogobin. Our studies have focused on elucidating the molecular mechanism of oxygen avidity, the basis of multimerization and the function of this remarkable molecule. We now believe that we understand a fair amount about the molecular interactions that result in enhanced avidity, have some preliminary ideas on octamer formation, and have some hypotheses about possible function. Along the way we have stumbled into the disciplines of intron evolution, sterol biosynthesis and oxygen-regulated gene expression.
    Additional Material: 3 Ill.
    Type of Medium: Electronic Resource
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