Publications
| Title | Abstract | Year(sorted ascending) Filter | PMID Filter |
|---|
| antiplasmodial and antitrypanosomal activity of new esters and ethers of 4-dialkylaminobicyclo[2.2.2]octan-2-ols. | only three drugs are available for the treatment of east african trypanosomiasis. patients suffer from painful application, severe side effects and increasing resistance against these drugs. malaria tropica kills more than 2 million people every year mainly due to growing drug resistance. 4-dialkylaminobicyclo[2.2.2]octan-2-ols and some of their esters have shown activity against both the causative organisms, trypanosoma brucei rhodesiense and plasmodium falciparum. ethers and new esters with ma ... | 2006 | 16713699 |
| basal body and flagellum mutants reveal a rotational constraint of the central pair microtubules in the axonemes of trypanosomes. | productive beating of eukaryotic flagella and cilia requires a strict regulation of axonemal dynein activation. fundamental to any description of axonemal beating is an understanding of the significance of the central pair microtubules and the degree to which central pair rotation has a role. however, for the majority of organisms, it is unclear whether the central pair actually rotates. using an extra-axonemal structure as a fixed reference, we analysed the orientation of the central pair in af ... | 2006 | 16720646 |
| effects of polyamines on two strains of trypanosoma brucei in infected rats and in vitro culture. | we studied the effects of polyamines, which are necessary for proliferation and antioxidation in trypanosoma brucei gambiense wellcome strain (ws) and trypanosoma brucei brucei iltat 1.4 strain (il). no difference was found in activity of ornithine decarboxylase (odc), a key enzyme in polyamine synthesis in trypanosomes, in both strains maintained in vitro; higher (p < 0.05) odc values were found in il in vivo. however, ws in vivo exhibited higher proliferation rates with higher spermidine conte ... | 2006 | 16729674 |
| efficacy of dipalmitoylphosphatidylcholine liposome against african trypanosomes. | we demonstrate here that dipalmitoylphosphatidylcholine (dppc) liposome has an antitrypanosomal effect, especially against the bloodstream forms (bsfs) of african trypanosomes (trypanosoma congolense, t. brucei rhodesiense, and t. brucei brucei). the dppc liposome significantly decreased the in vitro percentage of viable and motile bsf african trypanosomes but only marginally reduced the percentage of viable and motile procyclic form (pcf) of trypanosomes. the dppc liposome absorption was much m ... | 2006 | 16729700 |
| purification of an eight subunit rna polymerase i complex in trypanosoma brucei. | trypanosoma brucei harbors a unique multifunctional rna polymerase (pol) i which transcribes, in addition to ribosomal rna genes, the gene units encoding the major cell surface antigens variant surface glycoprotein and procyclin. in consequence, this rna pol i is recruited to three structurally different types of promoters and sequestered to two distinct nuclear locations, namely the nucleolus and the expression site body. this versatility may require parasite-specific protein-protein interactio ... | 2006 | 16730080 |
| the effect of down-regulation of mitochondrial rna-binding proteins mrp1 and mrp2 on respiratory complexes in procyclic trypanosoma brucei. | mrp1 and mrp2 are multifunctional mitochondrial rna-binding proteins with a regulatory role in rna editing and putative role(s) in rna processing in trypanosoma brucei. silencing of mrp1 and/or mrp2 by rna interference affected the assembly and functionality of respiratory complexes. the absence of several subunits of complexes i, iii and iv resulted in their disintegration and subsequent decrease of specific activities and also caused a significant decrease of membrane potential. the overall re ... | 2006 | 16730807 |
| evaluation of the anti-trypanosomal activity of tyropeptin a. | the natural compound tyropeptin a, a new peptidyl aldehyde proteasome inhibitor, was tested for its trypanocidal activity in vitro using culture-adapted bloodstream forms of trypanosoma brucei. the concentrations of tyropeptin a required to reduce the growth rate by 50 % and to kill all cells were 10 and 100 times lower for bloodstream-form trypanosomes than for human leukaemia hl-60 cells, respectively. enzymatic analysis showed that the trypsin-like activity of the trypanosome proteasome and t ... | 2006 | 16732530 |
| expression site silencing and life-cycle progression appear normal in argonaute1-deficient trypanosoma brucei. | 2006 | 16735068 | |
| effect of isometamidium chloride treatment on susceptibility of tsetse flies (diptera: glossinidae) to trypanosome infections. | experiments were conducted to determine the effect of a single isometamidium chloride treatment of teneral tsetse flies, glossina morsitans morsitans westwood (diptera: glossinidae), on the subsequent susceptibility to an infection with trypanosoma congolense or trypanosoma brucei brucei. flies were offered a first bloodmeal on sterile gamma-irradiated defibrinated bovine blood that contained either 10 or 100 microg ofisometamidium chloride/ml. treated flies were subsequently infected with t. co ... | 2006 | 16739416 |
| trypanosoma brucei glycosomal abc transporters: identification and membrane targeting. | trypanosomes contain unique peroxisome-like organelles designated glycosomes which sequester enzymes involved in a variety of metabolic processes including glycolysis. we identified three abc transporters associated with the glycosomal membrane of trypanosoma brucei. they were designated gat1-3 for glycosomal abc transporters. these polypeptides are so-called half-abc transporters containing only one transmembrane domain and a single nucleotide-binding domain, like their homologues of mammalian ... | 2006 | 16754359 |
| high-resolution complex of papain with remnants of a cysteine protease inhibitor derived from trypanosoma brucei. | attempts to cocrystallize the cysteine protease papain derived from the latex of carica papaya with an inhibitor of cysteine proteases (icp) from trypanosoma brucei were unsuccessful. however, crystals of papain that diffracted to higher resolution, 1.5 a, than other crystals of this archetypal cysteine protease were obtained, so the analysis was continued. surprisingly, the substrate-binding cleft was occupied by two short peptide fragments which have been assigned as remnants of icp. compariso ... | 2006 | 16754967 |
| molecular characterization of trypanosoma brucei p-type h+-atpases. | previous studies in trypanosoma brucei have shown that intracellular ph homeostasis is affected by inhibitors of h+-atpases, suggesting a major role for these pumps in this process (vander-heyden, n., wong, j., and docampo, r., (2000) biochem. j. 346, 53-62). here, we report the cloning and sequencing of three genes (tbha1, tbha2, and tbha3) present in the genome of t. brucei that encode proteins with homology to fungal and plant p-type proton-pumping atpases. northern and western blot analyses ... | 2006 | 16757482 |
| complete cap 4 formation is not required for viability in trypanosoma brucei. | in kinetoplastids spliced leader (sl) rna is trans-spliced onto the 5' ends of all nuclear mrnas, providing a universal exon with a unique cap. mature sl contains an m(7)g cap, ribose 2'-o methylations on the first four nucleotides, and base methylations on nucleotides 1 and 4 (aacu). this structure is referred to as cap 4. mutagenized sl rnas that exhibit reduced cap 4 are trans-spliced, but these mrnas do not associate with polysomes, suggesting a direct role in translation for cap 4, the prim ... | 2006 | 16757738 |
| dna binding affinity of bisguanidine and bis(2-aminoimidazoline) derivatives with in vivo antitrypanosomal activity. | a new antitrypanosomal hit compound that cures an acute (stib 900) mouse model of trypanosoma brucei rhodesiense trypanosomiasis is described. this bis(2-aminoimidazolinium) dicationic compound proved to be an excellent dna minor groove binder, suggesting a possible mechanism for its trypanocidal activity. from these studies, the 4,4'-diaminodiphenylamine skeleton emerged as a good scaffold for antitrypanosomal drugs. | 2006 | 16759117 |
| arginine methylation regulates mitochondrial gene expression in trypanosoma brucei through multiple effector proteins. | arginine methylation is a post-translational modification that impacts gene expression in both the cytoplasm and nucleus. here, we demonstrate that arginine methylation also affects mitochondrial gene expression in the protozoan parasite, trypanosoma brucei. down-regulation of the major trypanosome type i protein arginine methyltransferase, tbprmt1, leads to destabilization of specific mitochondrial mrnas. we provide evidence that some of these effects are mediated by the mitochondrial rna-bindi ... | 2006 | 16775306 |
| a post-assembly structural modification to the lumen of flagellar microtubule doublets. | 2006 | 16781996 | |
| telomerase-independent stabilization of short telomeres in trypanosoma brucei. | in cancer cells and germ cells, shortening of chromosome ends is prevented by telomerase. telomerase-deficient cells have a replicative life span, after which they enter senescence. senescent cells can give rise to survivors that maintain chromosome ends through recombination-based amplification of telomeric or subtelomeric repeats. we found that in trypanosoma brucei, critically short telomeres are stable in the absence of telomerase. telomere stabilization ensured genomic integrity and could h ... | 2006 | 16782879 |
| discovery of trypanocidal compounds by whole cell hts of trypanosoma brucei. | chemotherapy against human african trypanosomiasis relies on four drugs that cause frequent and occasionally severe side-effects. because human african trypanosomiasis is a disease of poor people in africa, the traditional market-driven pathways to drug development are not available. one potentially rapid and cost-effective approach to identifying and developing new trypanocidal drugs would be high throughput-screening of existing drugs already approved for other uses, as well as clinical candid ... | 2006 | 16784460 |
| determination of dihedral psi angles in large proteins by combining nh(n)/c(alpha)h(alpha) dipole/dipole cross-correlation and chemical shifts. | we propose a strategy based on the combination of experimental nh(n)/c(alpha)h(alpha) dipole/dipole cross-correlated relaxation rates and chemical shift analysis for the determination of psi torsion angles in proteins. the method allows the determination of a dihedral angle that is not easily accessible by nuclear magnetic resonance (nmr). the measurement of dihedral angle restraints can be used for structure calculation, which is known to improve the quality of nmr structures. the method is of ... | 2006 | 16786593 |
| ablation of the single dynamin of t. brucei blocks mitochondrial fission and endocytosis and leads to a precise cytokinesis arrest. | mitochondrial fission is mediated by dynamin-like proteins (dlps). trypanosoma brucei contains a single dlp, which is the only member of the dynamin superfamily. we have previously shown that expression of the human proapoptotic bax in t. brucei induces extensive mitochondrial fragmentation. here we report that baxinduced mitochondrial fission is abolished in cell lines lacking functional dlp suggesting that the protein is also required for mitochondrial division during the cell cycle. furthermo ... | 2006 | 16787942 |
| [new strategy in development of antibiotics: gpi biosynthesis as a target]. | 2006 | 16805320 | |
| the mitochondrial fad-dependent glycerol-3-phosphate dehydrogenase of trypanosomatidae and the glycosomal redox balance of insect stages of trypanosoma brucei and leishmania spp. | the genes for the mitochondrial fad-dependent glycerol-3-phosphate dehydrogenase were identified in trypanosoma brucei and leishmania major genomes. we have expressed the l. major gene in saccharomyces cerevisiae and confirmed the subcellular localization and activity of the produced enzyme. using cultured t. brucei procyclic and leishmania mexicana promastigote cells with a permeabilized plasma membrane and containing intact glycosomes, it was shown that dihydroxyacetone phosphate is converted ... | 2006 | 16806528 |
| analysis of neutral glycosphingolipids from trypanosoma brucei. | neutral glycosphingolipids (gsls) were isolated from trypanosoma brucei and analyzed by thin-layer chromatography (tlc), tlc/secondary ion mass spectrometry (tlc/sims), and liposome immune lysis assay (lila). three species of neutral gsls, designated as n-1, -2, and -3 were separated on tlc. n-1 gsl migrated very close to glucosylceramide (glccer) and n-2 gsl showed the same mobility as lactosylceramide (laccer). on the other hand, the mobility of n-3 gsl on the tlc plate was slower than globote ... | 2006 | 16806714 |
| aziridine-2,3-dicarboxylate inhibitors targeting the major cysteine protease of trypanosoma brucei as lead trypanocidal agents. | the protozoan parasite trypanosoma brucei causes human african trypanosomiasis, which is fatal if left untreated. due to the toxicity of currently used drugs and emerging drug resistance, there is an urgent need for novel therapies. the major trypanosome papain-like cysteine protease expressed by the parasite (e.g., rhodesain in t. b. rhodesiense) is considered an important target for the development of new trypanocidal drugs. series of aziridine-2,3-dicarboxylate-based cysteine protease inhibit ... | 2006 | 16516467 |
| the effect of tao expression on pcd-like phenomenon development and drug resistance in trypanosoma brucei. | drug resistance in trypanosoma brucei causes severe problems for people and domestic animals, but molecular mechanisms of the resistance are not well known. programmed cell death (pcd) is a fundamental process in both multicellular and unicellular organisms, and it is speculated to be one of the important factors contributing to the emergence of drug resistance. we have previously reported that the expression of tao appears to play a role in the inhibition of the pcd-like phenomenon development ... | 2006 | 16516538 |
| 2'-o-methylation of position 2 of the trypanosome spliced leader cap 4 is mediated by a 48 kda protein related to vaccinia virus vp39. | 2006 | 16516986 | |
| cell biology: when the tail wags the dog. | 2006 | 16525450 | |
| flagellar motility is required for the viability of the bloodstream trypanosome. | the 9 + 2 microtubule axoneme of flagella and cilia represents one of the most iconic structures built by eukaryotic cells and organisms. both unity and diversity are present among cilia and flagella on the evolutionary as well as the developmental scale. some cilia are motile, whereas others function as sensory organelles and can variously possess 9 + 2 and 9 + 0 axonemes and other associated structures. how such unity and diversity are reflected in molecular repertoires is unclear. the flagell ... | 2006 | 16525475 |
| a proteomic analysis of arsenical drug resistance in trypanosoma brucei. | we have undertaken 2-de and ms to identify proteins associated with arsenical drug resistance in trypanosoma brucei. this parasite causes sleeping sickness in humans, and arsenical drug resistance is a significant potential problem. comparative analysis of approximately 2000 spots resolved by 2-de in the soluble proteomes of drug-sensitive and drug-resistant isogenic lines of t. brucei identified a protein spot whose absence associated with resistance to the arsenical drug, cymelarsan. ms matche ... | 2006 | 16526094 |
| bacterial home from home. | 2006 | 16528802 | |
| enthalpy versus entropy-driven binding of bisphosphonates to farnesyl diphosphate synthase. | we report the results of an itc (isothermal titration calorimetry) investigation of the binding of six bisphosphonates to the enzyme farnesyl diphosphate synthase (fpps; ec 2.5.1.10) from trypanosoma brucei. the bisphosphonates investigated were zoledronate, risedronate, ibandronate, pamidronate, 2-phenyl-1-hydroxyethane-1,1-bisphosphonate, and 1-(2,2-bisphosphonoethyl)-3-iodo pyridinium. at ph = 7.4, both risedronate and the phenylethane bisphosphonate bind in an enthalpy-driven manner (deltah ... | 2006 | 16536518 |
| antitrypanosomal activity of 5'-deoxy-5'-(iodomethylene)adenosine and related 6-n-cyclopropyladenosine analogues. | treatment of the 6-n-cyclopropyl-2',3'-di-o-isopropylideneadenosine 5'-aldehyde with sulfone-stabilized phosphonate or fluorophosphonate reagents followed by stannyldesulfonylations and subsequent iodo- or protiodestannylation gave 6-n-cyclopropyl-5'-deoxy-5'-(iodomethylene)adenosine 8b or its 5'-fluoromethylene analogue 11. treatment of the 5'-aldehyde with hydroxylamine or dibromomethylene- or cyanomethylene-stabilized wittig reagents and deprotections gave the oxime 4b, 5'-cyanomethylene 5b, ... | 2006 | 16539398 |
| rapid identification of isometamidium-resistant stocks of trypanosoma b. brucei by pcr-rflp. | analyses were made on the adenosine transporter-1 gene in trypanosoma brucei (tbat1), encoding a p2-like nucleoside transporter, from t. brucei brucei field stocks to investigate a possible link between the presence of mutations in this gene and isometamidium resistance. we have analysed the gene from 11 isometamidium-sensitive field stocks isolated from cattle in uganda, two sensitive reference clones and two resistant reference clones. a sequence alignment showed that the isometamidium-sensiti ... | 2006 | 16541260 |
| in silico prediction of the glycosomal enzymes of leishmania major and trypanosomes. | in total, 37080 protein sequences of the three trypanosomatids leishmania major, trypanosoma brucei and trypanosoma cruzi, were used to predict the trypanosomatid glycosomal proteome. all protein sequences were analyzed for the presence of either a c-terminal (pts1) or an n-terminal (pts2) peroxisomal targeting sequence. for l. major 191 potential pts1-containing proteins and 68 potential pts2-containing proteins with homologues in t. brucei and t. cruzi were identified. about 50% of them were h ... | 2006 | 16546274 |
| trypanosoma cruzi mitochondrial maxicircles display species- and strain-specific variation and a conserved element in the non-coding region. | the mitochondrial dna of kinetoplastid flagellates is distinctive in the eukaryotic world due to its massive size, complex form and large sequence content. comprised of catenated maxicircles that contain rrna and protein-coding genes and thousands of heterogeneous minicircles encoding small guide rnas, the kinetoplast network has evolved along with an extreme form of mrna processing in the form of uridine insertion and deletion rna editing. many maxicircle-encoded mrnas cannot be translated with ... | 2006 | 16553959 |
| a tfiib-like protein is indispensable for spliced leader rna gene transcription in trypanosoma brucei. | the lack of general class ii transcription factors was a hallmark of the genomic sequences of the human parasites trypanosoma brucei, trypanosoma cruzi and leishmania major. however, the recent identification of tfiia as part of a protein complex essential for rna polymerase ii-mediated transcription of slrna genes, which encode the trans splicing-specific spliced leader rna, suggests that trypanosomatids assemble a highly divergent set of these factors at the slrna promoter. here we report the ... | 2006 | 16554554 |
| antitrypanosomal compounds from the leaf essential oil of strychnos spinosa. | the composition of the essential oil obtained by hydrodistillation of the leaves of strychnos spinosa (loganiaceae) was analysed by gc-fid and gc-ms. out of twenty-two compounds identified in the oil, the main constituents were palmitic acid (34.3%), linalool (16.0%), and (e)-phytol (6.7%). since the leaves of this plant are used in african traditional medicine to treat african trypanosomiasis, we evaluated the in vitro activity of the essential oil as well as of 15 of its components on trypanos ... | 2006 | 16557466 |
| a divergent transcription factor tfiib in trypanosomes is required for rna polymerase ii-dependent spliced leader rna transcription and cell viability. | transcription by rna polymerase ii in trypanosomes deviates from the standard eukaryotic paradigm. genes are transcribed polycistronically and subsequently cleaved into functional mrnas, requiring trans splicing of a capped 39-nucleotide leader rna derived from a short transcript, the spliced leader (sl) rna. the only identified trypanosome rna polymerase ii promoter is that of the sl rna gene. we have previously shown that transcription of sl rna requires divergent trypanosome homologs of rna p ... | 2006 | 16467470 |
| the rack1 homologue from trypanosoma brucei is required for the onset and progression of cytokinesis. | the receptor for activated c kinase 1 (rack1) is a conserved scaffold protein that helps regulate a range of cell activities including cell growth, shape, and protein translation. we report that a homologue of rack1 is required for cytokinesis in pathogenic trypanosoma brucei. the protein, referred to as track, is comprised of wd repeat elements and can complement cpc2 null mutants of schizosaccharomyces pombe. track is expressed throughout the trypanosome life cycle and is distributed predomina ... | 2006 | 16469736 |
| phosphatidylinositol synthesis is essential in bloodstream form trypanosoma brucei. | pi (phosphatidylinositol) is a ubiquitous eukaryotic phospholipid which serves as a precursor for messenger molecules and gpi (glycosylphosphatidylinositol) anchors. pi is synthesized either de novo or by head group exchange by a pis (pi synthase). the synthesis of gpi anchors has previously been validated both genetically and chemically as a drug target in trypanosoma brucei, the causative parasite of african sleeping sickness. however, nothing is known about the synthesis of pi in this organis ... | 2006 | 16475982 |
| characterization and selective inhibition of myristoyl-coa:protein n-myristoyltransferase from trypanosoma brucei and leishmania major. | the eukaryotic enzyme nmt (myristoyl-coa:protein n-myristoyltransferase) has been characterized in a range of species from saccharomyces cerevisiae to homo sapiens. nmt is essential for viability in a number of human pathogens, including the fungi candida albicans and cryptococcus neoformans, and the parasitic protozoa leishmania major and trypanosoma brucei. we have purified the leishmania and t. brucei nmts as active recombinant proteins and carried out kinetic analyses with their essential fa ... | 2006 | 16480339 |
| structural differences in triosephosphate isomerase from different species and discovery of a multitrypanosomatid inhibitor. | we examined the interfaces of homodimeric triosephosphate isomerase (tim) from eight different species. the crystal structures of the enzymes showed that a portion of the interface is markedly similar in tims from trypanosoma cruzi (tctim), trypanosoma brucei, and leishmania mexicana and significantly different from that of tims from human, yeast, chicken, plasmodium falciparum, and entamoeba histolytica. since this interfacial region is central in the stability of tctim, we hypothesized that it ... | 2006 | 16489748 |
| t. brucei rna editing: action of the u-insertional tutase within a u-deletion cycle. | trypanosome rna editing is massive post-transcriptional u-insertion and u-deletion, which generates mature mrna coding regions through cycles of endonuclease, terminal u transferase (tutase) or 3'-u-exo, and ligase action. both types of editing are thought to be catalyzed by distinct sets of proteins of a multiprotein complex, and no enzymatic activity of wild-type editing complex had been shown to function in both forms of editing. by examining the individual steps of the u-deletion cycle using ... | 2006 | 16495238 |
| bloodstream form trypanosoma brucei depend upon multiple metacaspases associated with rab11-positive endosomes. | trypanosoma brucei possesses five metacaspase genes. of these, mca2 and mca3 are expressed only in the mammalian bloodstream form of the parasite, whereas mca5 is expressed also in the insect procyclic form. triple rnai analysis showed mca2, mca3 and mca5 to be essential in the bloodstream form, with parasites accumulating pre-cytokinesis. nevertheless, triple null mutants (deltamca2/3deltamca5) could be isolated after sequential gene deletion. thereafter, deltamca2/3deltamca5 mutants were found ... | 2006 | 16507595 |
| selective irreversible inhibition of fructose 1,6-bisphosphate aldolase from trypanosoma brucei. | an irreversible competitive inhibitor hydroxynaphthaldehyde phosphate was synthesized that is highly selective against the glycolytic enzyme fructose 1,6-bisphosphate aldolase from trypanosoma brucei (causative agent of sleeping sickness). inhibition involves schiff base formation by the inhibitor aldehyde with lys116 followed by reaction of the resultant schiff base with a second residue. molecular simulations indicate significantly greater molecular geometries conducive for nucleophilic attack ... | 2006 | 16509566 |
| removal or maintenance of inositol-linked acyl chain in glycosylphosphatidylinositol is critical in trypanosome life cycle. | the protozoan parasite trypanosoma brucei is coated by glycosylphosphatidylinositol (gpi)-anchored proteins. during gpi biosynthesis, inositol in phosphatidylinositol becomes acylated. inositol is deacylated prior to attachment to variant surface glycoproteins in the bloodstream form, whereas it remains acylated in procyclins in the procyclic form. we have cloned a t. brucei gpi inositol deacylase (gpideac2). in accordance with the acylation/deacylation profile, the level of gpideac2 mrna was 6- ... | 2006 | 16510441 |
| functional characterisation of the iron superoxide dismutase gene repertoire in trypanosoma brucei. | superoxide dismutases (sod) are a family of antioxidant enzymes that function by removing superoxide anions from the cellular environment. here, we show that the african trypanosome, trypanosoma brucei, expresses four sod isoforms, three of which we have validated biochemically as iron dependent, a feature normally associated with prokaryotic sods. localisation studies reveal that two of the enzymes are found predominantly in a parasite-specific organelle, the glycosome (tbsodb1 and tbsodb2), wh ... | 2006 | 16413403 |
| the presence of four iron-containing superoxide dismutase isozymes in trypanosomatidae: characterization, subcellular localization, and phylogenetic origin in trypanosoma brucei. | metalloenzymes such as the superoxide dismutases (sods) form part of a defense mechanism that helps protect obligate and facultative aerobic organisms from oxygen toxicity and damage. here, we report the presence in the trypanosomatid genomes of four sod genes: soda, sodb1, sodb2, and a newly identified sodc. all four genes of trypanosoma brucei have been cloned (tbsods), sequenced, and overexpressed in escherichia coli and shown to encode active dimeric fesod isozymes. homology modeling of the ... | 2006 | 16413404 |
| mechanistic analysis of a multiple product sterol methyltransferase implicated in ergosterol biosynthesis in trypanosoma brucei. | sterol methyltransferase (smt) plays a key role in sterol biosynthesis in different pathogenic organisms by setting the pattern of the side chain structure of the final product. this catalyst, absent in humans, provides critical pathway-specific enzymatic steps in the production of ergosterol in fungi or phytosterols in plants. the new smt gene was isolated from trypanosoma brucei genomic dna and cloned into an escherichia coli expression system. the recombinant smt was purified to homogeneity t ... | 2006 | 16414960 |
| bioactive properties of plant species ingested by chimpanzees (pan troglodytes schweinfurthii) in the kibale national park, uganda. | we measured the biological activities of a selected sample (84 crude extracts) of 24 species eaten by wild chimpanzees (pan troglodytes schweinfurthii) in the kibale national park, western uganda, to assess their potential chemotherapeutic values. antibacterial, antimalarial, and/or antileishmania activities were observed in some crude extracts, and five of these extracts showed a significant cytotoxicity against human tumor cells. active compounds isolated from three plant parts occasionally in ... | 2006 | 16419122 |
| gene transcription in trypanosomes. | trypanosoma brucei and the other members of the trypanosomatid family of parasitic protozoa, contain an unusual rna polymerase ii enzyme, uncoordinated mrna 5' capping and transcription initiation events, and most likely contain an abridged set of transcription factors. pre-mrna start sites remain elusive. in addition, two important life cycle stage-specific mrnas are transcribed by rna polymerase i. this review interprets these unusual transcription traits in the context of parasite biology. | 2006 | 16427709 |
| characterization of a trypanosoma brucei rna cap (guanine n-7) methyltransferase. | the m7gpppn cap structure of eukaryotic mrna is formed by the sequential action of rna triphosphatase, guanylyltransferase, and (guanine n-7) methyltransferase. in trypanosomatid protozoa, the m7gpppn is further modified by seven methylation steps within the first four transcribed nucleosides to form the cap 4 structure. the rna triphosphatase and guanylyltransferase components have been characterized in trypanosoma brucei. here we describe the identification and characterization of a t. brucei ... | 2006 | 16431985 |
| an aurora kinase homologue is involved in regulating both mitosis and cytokinesis in trypanosoma brucei. | the chromosomal passenger protein aurora kinases have been implicated in regulating chromosome segregation and cell division. three aurora kinase homologues were identified (tbauk1, -2 and -3) in the trypanosome genomic data base, and their expressions in the procyclic form of trypanosoma brucei were knocked down individually by using the rna interference technique. only a knockdown of tbauk1 arrested the cells in g(2)/m phase with each cell showing an extended posterior end, two kinetoplasts, a ... | 2006 | 16436376 |
| isoflavonoids and other compounds from psorothamnus arborescens with antiprotozoal activities. | bioactivity-guided fractionation of the root extract of psorothamnus arborescens yielded the new isoflavone 5,7,3',4'-tetrahydroxy-2'-(3,3-dimethylallyl)isoflavone (1a) and the new 2-arylbenzofuran 2-(2'-hydroxy-4',5'-methylenedioxyphenyl)-6-methoxybenzofuran-3-carbaldehyde (2), together with seven known compounds, including three isoflavones, fremontin (3a), glycyrrhisoflavone (4a), and calycosin (5), two pterocarpans, maackiain (6) and 4-hydroxymaackiain (7), one triterpene, oleanolic acid (8) ... | 2006 | 16441066 |
| 3d qsar on a library of heterocyclic diamidine derivatives with antiparasitic activity. | african trypanosomes, trypanosoma brucei rhodesiense (tbr) and trypanosoma brucei gambiense (tbg), affect hundreds of thousands of lives in tropical regions of the world. the toxicity of the diamidine pentamidine, an effective drug against tbg, necessitates the design of better drugs. an orally effective prodrug of the diamidine, furamidine (db75), presently scheduled for phase iii clinical trials, has excellent activity against tbg with toxicity lower than that of pentamidine. as part of an eff ... | 2006 | 16442293 |
| prostaglandin-induced programmed cell death in trypanosoma brucei involves oxidative stress. | recently, we reported the induction of a programmed cell death (pcd) in bloodstream forms of trypanosoma brucei by prostaglandin d(2) (pgd(2)). as this prostanoid is readily metabolized in the presence of albumin, we were prompted to investigate if pgd(2) metabolites rather than pgd(2) itself are responsible for the observed pcd. in fact, j series metabolites, especially pgj(2) and delta(12)pgj(2), were able to induce pcd more efficiently than pgd(2). however, the stable pgd(2) analog 17phenyl-t ... | 2006 | 16456581 |
| trypanocidal activity of methylene blue. evidence for in vitro efficacy and in vivo failure. | human african trypanosomiasis remains a difficult health problem to treat because of the few compounds available nowadays and their toxicity. the disease also affects animals and is therefore responsible for economic difficulties and zoonotic risks. there is an urgent need to develop new drugs for treatment of african trypanosomiasis. methylene blue is a safe and easy-to-use drug employed in human therapy. it is also known to have antimalarial activity. in this study, methylene blue trypanocidal ... | 2006 | 16340192 |
| the role of trypanosoma brucei mrpa in melarsoprol susceptibility. | we previously showed that over-expression of trypanosoma brucei mrpa, a member of the multidrug resistance protein family in t. brucei, reproducibly resulted in resistance to the anti-trypanosomal drug melarsoprol in vitro. mrpa is predicted to mediate efflux of melarsoprol as a conjugate with trypanothione, a glutathione-spermidine conjugate which is the major small thiol in trypanosomes. here, we show that depletion of mrpa by rna interference resulted in moderate hypersensitivity to both mela ... | 2006 | 16343658 |
| the ornithine decarboxylase gene of trypanosoma brucei: evidence for horizontal gene transfer from a vertebrate source. | kinetoplastid protozoans in the family trypanosomatidae are parasites, many of them responsible for serious diseases in humans and domestic animals. ornithine decarboxlyase (odc), a protein at the core of polyamine metabolism, is a potential target for therapies to overcome these diseases. eukaryotic phylogenies were constructed from full-length genes for odc to determine the origin of odc in the kinetoplastid protozoans. the odc genes from trypanosoma brucei and two other african trypanosomes, ... | 2006 | 16344004 |
| biosynthesis and uptake of thiamine (vitamin b1) in bloodstream form trypanosoma brucei brucei and interference of the vitamin with melarsen oxide activity. | bloodstream forms of trypanosoma brucei brucei were cultivated in the presence and absence of thiamine (vitamin b1) and pyridoxine (vitamin b6). the vitamins do not change growth behaviour, indicating that trypanosoma brucei is prototrophic for the two vitamins even though in silico no bona-fide thiamine-biosynthetic genes could be identified in the t. brucei genome. intracellularly, thiamine is mainly present in its diphosphate form. we were unable to detect significant uptake of [3h]thiamine a ... | 2006 | 16375907 |
| doubts about trypanosoma equiperdum strains classed as trypanosoma brucei or trypanosoma evansi. | 2006 | 16377246 | |
| identification and characterization of three peroxins--pex6, pex10 and pex12--involved in glycosome biogenesis in trypanosoma brucei. | protozoan kinetoplastida such as the pathogenic trypanosomes compartmentalize several important metabolic systems, including the glycolytic pathway, in peroxisome-like organelles designated glycosomes. genes for three proteins involved in glycosome biogenesis of trypanosoma brucei were identified. a preliminary analysis of these proteins, the peroxins pex6, pex10 and pex12, was performed. cellular depletion of these peroxins by rna interference affected growth of both mammalian bloodstream-form ... | 2006 | 16388862 |
| a diminazene-resistant strain of trypanosoma brucei brucei isolated from a dog is cross-resistant to pentamidine in experimentally infected albino rats. | trypanosomosis is a major cause of mortality for dogs in nigeria and treatment with diminazene aceturate has steadily become less effective, either as a result of low quality of the locally available diminazene preparations or of drug resistance. to investigate these alternatives, samples of locally obtained drugs were analysed for diminazene aceturate content and a strain of trypanosoma brucei brucei was isolated from a diminazene-refractory dog in nsukka, south-eastern nigeria, and used to inf ... | 2006 | 16393361 |
| multiple effects of the lectin-inhibitory sugars d-glucosamine and n-acetyl-glucosamine on tsetse-trypanosome interactions. | we are studying early events in the establishment of trypanosoma brucei in the tsetse midgut using fluorescent trypanosomes to increase visibility. feeding flies with the lectin-inhibitory sugars d-glucosamine (glcn) or n-acetyl-glucosamine (glcnac) has previously been shown to enhance fly susceptibility to infection with trypanosomes and, as expected, we found that both sugars increased midgut infection rates of glossina morsitans morsitans with t. brucei. however, glcnac did not show the inhib ... | 2006 | 16393366 |
| atp synthase is responsible for maintaining mitochondrial membrane potential in bloodstream form trypanosoma brucei. | the mitochondrion of trypanosoma brucei bloodstream form maintains a membrane potential, although it lacks cytochromes and several krebs cycle enzymes. at this stage, the atp synthase is present at reduced, although significant, levels. to test whether the atp synthase at this stage is important for maintaining the mitochondrial membrane potential, we used rna interference (rnai) to knock down the levels of the atp synthase by targeting the f1-atpase alpha and beta subunits. rnai-induced cells g ... | 2006 | 16400167 |
| dissociation of cytokinesis initiation from mitotic control in a eukaryote. | cytokinesis is initiated only after mitotic exit in eukaryotes. however, in the insect (procyclic) form of an ancient protist, trypanosoma brucei, a blockade at the g2/m checkpoint results in an enrichment of anucleate cells (zoids), suggesting separated regulations between mitosis and cytokinesis (x. tu and c. c. wang, j. biol. chem. 279:20519-20528, 2004). polo-like kinases (plks) are known to play critical roles in controlling both mitosis and cytokinesis. a single plk homologue in t. brucei, ... | 2006 | 16400171 |
| serum resistance-associated protein blocks lysosomal targeting of trypanosome lytic factor in trypanosoma brucei. | trypanosoma brucei brucei is the causative agent of nagana in cattle and can infect a wide range of mammals but is unable to infect humans because it is susceptible to the innate cytotoxic activity of normal human serum. a minor subfraction of human high-density lipoprotein (hdl) containing apolipoprotein a-i (apoa-i), apolipoprotein l-i (apol-i), and haptoglobin-related protein (hpr) provides this innate protection against t. b. brucei infection. this hdl subfraction, called trypanosome lytic f ... | 2006 | 16400175 |
| tbgpi16 is an essential component of gpi transamidase in trypanosoma brucei. | glycosylphosphatidylinositol (gpi) is widely used by eukaryotic cell surface proteins for membrane attachment. de novo synthesized gpi precursors are attached to proteins post-translationally by the enzyme complex, gpi transamidase. tbgpi16, a component of the trypanosome transamidase, shares similarity with human pig-t. here, we show that tbgpi16 is the orthologue of pig-t and an essential component of gpi transamidase by creating a tbgpi16 knockout. tbgpi16 forms a disulfide-linked complex wit ... | 2006 | 16405969 |
| evaluation of medicinal plants from mali for their in vitro and in vivo trypanocidal activity. | water, methanol and dichloromethane extracts prepared from various parts of 40 medicinal plant species from mali were investigated for their trypanocidal activity against trypanosoma brucei brucei. of a total of 165 extracts tested in vitro in the low inoculation long incubation test (lilit), 24 extracts showed a high trypanocidal activity. using the long-term viability assay (ltva) for corroboration of the results of the 24 extracts, it was found that 15 samples had minimum inhibitory concentra ... | 2006 | 16188409 |
| new fluorescence markers to distinguish co-infecting trypanosoma brucei strains in experimental multiple infections. | multiple-genotype infections are increasingly recognized as important factors in disease evolution, parasite transmission dynamics, and the evolution of drug resistance. however, the distinction of co-infecting parasite genotypes and the tracking of their dynamics have been difficult with traditional methods based on various genotyping techniques, leaving most questions unaddressed. here we report new fluorescence markers of various colours that are inserted into the genome of trypanosoma brucei ... | 2006 | 16212925 |
| analysis of spliceosomal complexes in trypanosoma brucei and silencing of two splicing factors prp31 and prp43. | in trypanosomatids all mrnas undergo trans-splicing, whereas cis-splicing is restricted to a few transcripts. trans-splicing is mechanistically similar to cis-splicing, however, little is known about the trans-splicing machinery and its underlying mechanism. in this study, we examined the involvement of splicing factors in cis- and trans-splicing by rna interference (rnai). two factors (prp31 and prp43) were found to be essential for both pathways, suggesting that splicing factors are shared by ... | 2006 | 16219373 |
| distinct genes encode type ii topoisomerases for the nucleus and mitochondrion in the protozoan parasite trypanosoma brucei. | topoisomerases are essential for orderly nucleic acid metabolism and cell survival and are proven targets for clinically useful antimicrobial and anticancer drugs. interest in the topologically intricate mitochondrial dna (kinetoplast or kdna) of trypanosoma brucei brucei and related kinetoplastid protozoan parasites has led to many reports of type ii topoisomerases that participate in kdna metabolism (we term the t. brucei brucei gene tbtop2mt). we have now identified and characterized two new ... | 2006 | 16316982 |
| the malate dehydrogenase isoforms from trypanosoma brucei: subcellular localization and differential expression in bloodstream and procyclic forms. | trypanosoma brucei procyclic forms possess three different malate dehydrogenase isozymes that could be separated by hydrophobic interaction chromatography and were recognized as the mitochondrial, glycosomal and cytosolic malate dehydrogenase isozymes. the latter is the only malate dehydrogenase expressed in the bloodstream forms, thus confirming that the expression of malate dehydrogenase isozymes is regulated during the t. brucei life cycle. to achieve further biochemical characterization, the ... | 2006 | 16321390 |
| ubiquitination of plasma membrane ectophosphatase in bloodstream forms of trypanosoma brucei. | bloodstream forms of trypanosoma brucei contain plasma-membrane-integral acidic ectophosphatase. here, it is shown by n-terminal sequencing that the ectophosphatase found in ricin-binding material was modified by ubiquitin. three different ubiquitinated species corresponding to single, double and triple ubiquitinated forms of the enzyme were identified. immunofluorescence studies with live bloodstream-form parasites showed that the ectophosphatase was localized in the flagellar pocket-the sole s ... | 2006 | 16308729 |
| synthesis and antiprotozoal activity of some new synthetic substituted quinoxalines. | a series of 29 new quinoxalines was synthesized and evaluated in vitro against several parasites (leishmania donovani, trypanosoma brucei brucei, and trichomonas vaginalis). several of them displayed interesting activities, and particularly four quinoxaline amides showed in vitro antileishmanial properties (ic50 less than 20 microm). | 2006 | 16309903 |
| biphasic decay of guide rnas in trypanosoma brucei. | guide rnas (grnas) are short mitochondrially encoded rnas that contain the information for editing of messenger rnas in trypanosoma brucei. although a great deal of work has focused on the utilization of grnas in editing, little is known about the turnover of grnas. in this report, we utilized in organello pulse chase and in vitro rna decay experiments to directly examine grna turnover. we found that grnas are degraded by a biphasic mechanism. in the first step of decay, 3' grna sequences encomp ... | 2006 | 16310873 |
| repression of polymerase i-mediated gene expression at trypanosoma brucei telomeres. | the african trypanosome, trypanosoma brucei, is a flagellated pathogenic protozoan that branched early from the eukaryotic lineage. unusually, it uses rna polymerase i (pol i) for mono-telomeric expression of variant surface glycoprotein (vsg) genes in bloodstream-form cells. many other subtelomeric vsg genes are reversibly repressed, but no repressive dna sequence has been identified in any trypanosomatid. here, we show that artificially seeded de novo telomeres repress pol i-dependent gene exp ... | 2006 | 16311518 |
| the viper elements of trypanosomes constitute a novel group of tyrosine recombinase-enconding retrotransposons. | viper was initially characterized as a 2326bp ltr-like retroelement associated to sire, a short interspersed repetitive element specific of trypanosoma cruzi. it carried a single orf that coded for a putative reverse transcriptase-rnase h protein, suggesting that it could be a truncated copy of a longer retroelement. herein we report the identification and characterization of a complete 4480bp long viper in the t. cruzi genome. the complete viper harbored three non-overlapped domains encoding fo ... | 2006 | 16297462 |
| a vector series for rapid pcr-mediated c-terminal in situ tagging of trypanosoma brucei genes. | 2006 | 16269191 | |
| c to u editing stimulates a to i editing in the anticodon loop of a cytoplasmic threonyl trna in trypanosoma brucei. | editing of trnas is widespread in nature and either changes the decoding properties or restores the folding of a trna. unlike the phylogenetically disperse adenosine (a) to inosine (i) editing, cytosine (c) to uridine (u) editing has only been previously described in organellar trnas. we have shown that cytoplasmic trna(thr)(agu) undergoes two distinct editing events in the anticodon loop: c to u and a to i. in vivo, every inosine-containing trna(thr) is also c to u edited at position 32. in vit ... | 2006 | 16269406 |
| a protein related to the vaccinia virus cap-specific methyltransferase vp39 is involved in cap 4 modification in trypanosoma brucei. | the spliced-leader (sl) rna plays a key role in the biogenesis of mrna in trypanosomes by providing the m(7)g-capped sl sequence to the 5' end of every mrna. the cap structure of the sl rna is unique in eukaryotes with 4 nucleotides after the cap carrying a total of seven methyl groups and by convention is referred to as "cap 4". although the enzymatic machinery for cap addition has been characterized in several organisms, including trypanosoma brucei, the identification of methyltransferases de ... | 2006 | 16301606 |
| visualisation and analysis of proteomic data from the procyclic form of trypanosoma brucei. | we have undertaken a large scale study of the proteins expressed in the procyclic form of the parasite trypanosoma brucei, which causes african sleeping sickness, using 2-de and ms. the complete data set encompasses over 2000 identifications, of which 770 are distinct proteins. we have discovered that multiple protein isoforms appear to be common in t. brucei, as most proteins have been matched to more than one gel spot. we have developed visualisation software to investigate the differences bet ... | 2006 | 16302277 |
| time-dependent inhibitors of trypanothione reductase: analogues of the spermidine alkaloid lunarine and related natural products. | the macrocyclic spermidine alkaloid lunarine 1 from lunaria biennis is a competitive, time-dependent inhibitor of the protozoan oxidoreductase trypanothione reductase (tryr), a promising target in drug design against tropical parasitic diseases. various molecules related to 1 and the alkaloid itself have been synthesized in racemic form and evaluated against tryr in order to determine the key features of 1 that are associated with time-dependent inhibition. kinetic data are consistent with an in ... | 2006 | 16303308 |
| chemotherapeutic efficacy of ascofuranone in trypanosoma vivax-infected mice without glycerol. | ascofuranone, an antibiotic isolated from ascochyta visiae, showed trypanocidal activity in trypanosoma vivax-infected mice. a single dose of 50 mg/kg ascofuranone effectively cured the mice without the help of glycerol. repeated administrations of this drug further enhanced its chemotherapeutic effect. after two, three, and four consecutive days treatment, the doses needed to cure the infection decreased to 25, 12, and 6 mg/kg, so that the total doses administered were 50, 36 and 24 mg/kg, resp ... | 2006 | 16288933 |
| trypanosoma brucei dmc1 does not act in dna recombination, repair or antigenic variation in bloodstream stage cells. | homologous recombination acts in the repair of cellular dna damage and can generate genetic variation. some of this variation provides a discrete purpose in the cell, although it can also be genome-wide and contribute to longer-term natural selection. in trypanosoma brucei, a eukaryotic parasite responsible for sleeping sickness disease in sub-saharan africa, homologous recombination acts to catalyse antigenic variation, an immune evasion strategy involving switches in variant surface glycoprote ... | 2006 | 16289356 |
| pyroglutamyl peptidase type i from trypanosoma brucei: a new virulence factor from african trypanosomes that de-blocks regulatory peptides in the plasma of infected hosts. | peptidases of parasitic protozoans are emerging as novel virulence factors and therapeutic targets in parasitic infections. a trypanosome-derived aminopeptidase that exclusively hydrolysed substrates with glp (pyroglutamic acid) in p1 was purified 9248-fold from the plasma of rats infected with trypanosoma brucei brucei. the enzyme responsible was cloned from a t. brucei brucei genomic dna library and identified as type i pgp (pyroglutamyl peptidase), belonging to the c15 family of cysteine pept ... | 2006 | 16248854 |
| evolution of non-ltr retrotransposons in the trypanosomatid genomes: leishmania major has lost the active elements. | the ingi and l1tc non-ltr retrotransposons--which constitute the ingi clade--are abundant in the genome of the trypanosomatid species trypanosoma brucei and trypanosoma cruzi, respectively. the corresponding retroelements, however, are not present in the genome of a closely related trypanosomatid, leishmania major. to study the evolution of non-ltr retrotransposons in trypanosomatids, we have analyzed all ingi/l1tc elements and highly degenerate ingi/l1tc-related sequences identified in the rece ... | 2006 | 16257065 |
| role of p38 in replication of trypanosoma brucei kinetoplast dna. | trypanosomes have an unusual mitochondrial genome, called kinetoplast dna, that is a giant network containing thousands of interlocked minicircles. during kinetoplast dna synthesis, minicircles are released from the network for replication as theta-structures, and then the free minicircle progeny reattach to the network. we report that a mitochondrial protein, which we term p38, functions in kinetoplast dna replication. rna interference (rnai) of p38 resulted in loss of kinetoplast dna and accum ... | 2006 | 16809774 |
| the glycosylphosphatidylinositol (gpi) biosynthetic pathway of bloodstream-form trypanosoma brucei is dependent on the de novo synthesis of inositol. | in bloodstream-form trypanosoma brucei (the causative agent of african sleeping sickness) the glycosylphosphatidylinositol (gpi) anchor biosynthetic pathway has been validated genetically and chemically as a drug target. the conundrum that gpi anchors could not be in vivo labelled with [3h]-inositol led us to hypothesize that de novo synthesis was responsible for supplying myo-inositol for phosphatidylinositol (pi) destined for gpi synthesis. the rate-limiting step of the de novo synthesis is th ... | 2006 | 16824097 |
| tbvps34, the trypanosome orthologue of vps34, is required for golgi complex segregation. | phosphoinositides are important regulators of numerous cellular functions. the yeast class iii phosphatidylinositol 3-kinase vps34p, and its human orthologue hvps34, are implicated in control of several key pathways, including endosome to lysosome transport, retrograde endosome to golgi traffic, multivesicular body formation, and autophagy. we have identified the vps34p orthologue in the african trypanosome, tbvps34. knockdown of tbvps34 expression by rna interference induces a severe growth def ... | 2006 | 16835237 |
| changing roles of aurora-b kinase in two life cycle stages of trypanosoma brucei. | aurora-b kinase is a chromosomal passenger protein essential for chromosome segregation and cytokinesis. in the procyclic form of trypanosoma brucei, depletion of an aurora-b kinase homologue tbauk1 inhibited spindle formation, mitosis, cytokinesis, and organelle replication without altering cell morphology. in the present study, an rna interference knockdown of tbauk1 or overexpression of inactive mutant tbauk1-k58r in the bloodstream form also resulted in defects in spindle formation, chromoso ... | 2006 | 16835447 |
| a mitogen-activated protein kinase controls differentiation of bloodstream forms of trypanosoma brucei. | african trypanosomes undergo differentiation in order to adapt to the mammalian host and the tsetse fly vector. to characterize the role of a mitogen-activated protein (map) kinase homologue, tbmapk5, in the differentiation of trypanosoma brucei, we constructed a knockout in procyclic (insect) forms from a differentiation-competent (pleomorphic) stock. two independent knockout clones proliferated normally in culture and were not essential for other life cycle stages in the fly. they were also ab ... | 2006 | 16835456 |
| identification of pentatricopeptide repeat proteins in trypanosoma brucei. | a new class of organellar proteins, characterized by pentatricopeptide repeat (ppr) motifs, has been identified in plants. these proteins contain multiple 35-amino acid repeats that are proposed to form a super helix capable of binding a strand of rna. all ppr proteins characterized to date appear to be involved in rna processing pathways in organelles. twenty-three ppr proteins have been identified in trypanosoma brucei and database research indicates that most of these proteins are predicted t ... | 2006 | 16837079 |
| the function of apolipoproteins l. | the function of the proteins of the apolipoprotein l (apol) family is largely unknown. these proteins are classically thought to be involved in lipid transport and metabolism, mainly due to the initial discovery that a secreted member of the family, apol-i, is associated with high-density lipoprotein particles. however, the other members of the family are believed to be intracellular. the recent unravelling of the mechanism by which apol-i kills african trypanosomes, as well as the increasing ev ... | 2006 | 16847577 |
| fumarate is an essential intermediary metabolite produced by the procyclic trypanosoma brucei. | the procyclic stage of trypanosoma brucei, a parasitic protist responsible for sleeping sickness in humans, converts most of the consumed glucose into excreted succinate, by succinic fermentation. succinate is produced by the glycosomal and mitochondrial nadh-dependent fumarate reductases, which are not essential for parasite viability. to further explore the role of the succinic fermentation pathways, we studied the trypanosome fumarases, the enzymes providing fumarate to fumarate reductases. t ... | 2006 | 16857679 |
| preferential interaction of a 25kda protein with an a6 pre-mrna substrate for rna editing in trypanosoma brucei. | mitochondrial gene expression in kinetoplastids is controlled after transcription, potentially at the levels of rna maturation, stability and translation. among these processes, rna editing by u-insertion/deletion catalysed by multi-subunit editing complexes is best characterised at the molecular level. nevertheless, mitochondrial rna metabolism overall remains poorly understood, including the potential regulatory factors that may interact with the relevant catalytic molecular machines and/or rn ... | 2006 | 16860325 |
| new azasterols against trypanosoma brucei: role of 24-sterol methyltransferase in inhibitor action. | a series of azasterol derivatives, designed as potential inhibitors of the delta(24)-sterol methyltransferase enzyme (24-smt), were synthesized and evaluated for their activities against parasitic protozoa. values in the nanomolar range were obtained for 50% effective dose against the trypanosoma brucei subsp. rhodesiense bloodstream form cultured in vitro. in order to investigate the mode of action, trypanosoma brucei subsp. brucei 24-smt was cloned and overexpressed and compounds were assayed ... | 2006 | 16870747 |
| expression, purification and preliminary crystallographic analysis of oligopeptidase b from trypanosoma brucei. | african sleeping sickness, also called trypanosomiasis, is a significant cause of morbidity and mortality in sub-saharan africa. peptidases from trypanosoma brucei, the causative agent, include the serine peptidase oligopeptidase b, a documented virulence factor and therapeutic target. determination of the three-dimensional structure of oligopeptidase b is desirable to facilitate the development of novel inhibitors. oligopeptidase b was overexpressed in escherichia coli as an n-terminally hexahi ... | 2006 | 16880564 |
| knock-downs of iron-sulfur cluster assembly proteins iscs and iscu down-regulate the active mitochondrion of procyclic trypanosoma brucei. | transformation of the metabolically down-regulated mitochondrion of the mammalian bloodstream stage of trypanosoma brucei to the atp-producing mitochondrion of the insect procyclic stage is accompanied by the de novo synthesis of citric acid cycle enzymes and components of the respiratory chain. because these metabolic pathways contain multiple iron-sulfur (fes) proteins, their synthesis, including the formation of fes clusters, is required. however, nothing is known about fes cluster biogenesis ... | 2006 | 16882667 |
| conserved and specific functions of axoneme components in trypanosome motility. | the trypanosoma brucei flagellum is unusual as it is attached along the cell body and contains, in addition to an apparently conventional axoneme, a structure called the paraflagellar rod, which is essential for cell motility. here, we investigated flagellum behaviour in normal and mutant trypanosome cell lines where expression of genes encoding various axoneme proteins (pf16, pf20, dnai1, lc2) had been silenced by rnai. first, we show that the propulsive wave (normally used for forward motility ... | 2006 | 16882690 |