| ammonia permeability of the aquaglyceroporins from plasmodium falciparum, toxoplasma gondii and trypansoma brucei. | plasmodium falciparum uses amino acids from haemoglobin degradation mainly for protein biosynthesis. glutamine, however, is mostly oxidized to 2-oxoglutarate to restore nad(p)h + h+. in this process two molecules of ammonia are released. we determined an ammonia production of 9 mmol h(-1) per litre of infected red blood cells in the early trophozoite stage. external application of ammonia yielded a cytotoxic ic50 concentration of 2.8 mm. as plasmodia cannot metabolize ammonia it must be exported ... | 2006 | 16889642 |
| antiprotozoal activities of new bis-chlorophenyl derivatives of bicyclic octanes and aza-nonanes. | the in vitro activity of newly synthesized bis-(chlorophenyl)-azabicyclo[3.2.2]nonanes and bis-(chlorophenyl)-bicyclo[2.2.2]octanes against plasmodium falciparum k(1) (resistant to chloroquine and pyrimethamine) and trypanosoma brucei rhodesiense was investigated. especially the bis-(chlorophenyl)-azabicyclo[3.2.2]nonanes exhibit promising antitrypanosomal activity and were tested in vivo against trypanosoma brucei brucei featuring moderate activities. | 2006 | 16889962 |
| inhibitors of casein kinase 1 block the growth of leishmania major promastigotes in vitro. | casein kinase 1 (ck1) is a family of multifunctional ser/thr protein kinases that are ubiquitous in eukaryotic cells. recent studies have demonstrated the existence of, and role for, ck1 in protozoan parasites such as leishmania, plasmodium and trypanosoma. the value of protein kinases as potential drug targets in protozoa is evidenced by the successful exploitation of cyclic guanosine monophosphate-dependent protein kinase (pkg) with selective tri-substituted pyrrole and imidazopyridine inhibit ... | 2006 | 16890941 |
| molecular dipstick test for diagnosis of sleeping sickness. | human african trypanosomiasis (hat) or sleeping sickness is a neglected disease that affects poor rural populations across sub-saharan africa. confirmation of diagnosis is based on detection of parasites in either blood or lymph by microscopy. here we present the development and the first-phase evaluation of a simple and rapid test (hat-pcr-oc [human african trypanosomiasis-pcr-oligochromatography]) for detection of amplified trypanosoma brucei dna. pcr products are visualized on a dipstick thro ... | 2006 | 16891507 |
| characterization and developmentally regulated localization of the mitochondrial carrier protein homologue mcp6 from trypanosoma brucei. | proteins of the mitochondrial carrier family (mcf) are located mainly in the inner mitochondrial membrane and mediate the transport of a large range of metabolic intermediates. the genome of trypanosoma brucei harbors 29 genes encoding different mcf proteins. we describe here the characterization of mcp6, a novel t. brucei mcf protein. sequence comparison and phylogenetic reconstruction revealed that mcp6 is closely related to different mitochondrial adp/atp and calcium-dependent solute carriers ... | 2006 | 16896205 |
| sorting signals required for trafficking of the cysteine-rich acidic repetitive transmembrane protein in trypanosoma brucei. | in trypanosomatids, endocytosis and exocytosis are restricted to the flagellar pocket (fp). the cysteine-rich acidic repetitive transmembrane (cram) protein is located at the fp of trypanosoma brucei and potentially functions as a receptor or an essential component for lipoprotein uptake. we characterized sorting determinants involved in efficient trafficking of cram to and from the fp of t. brucei. previous studies indicated the presence of signals in the cram c terminus, specific for its local ... | 2006 | 16896208 |
| in vitro generation of human high-density-lipoprotein-resistant trypanosoma brucei brucei. | the host range of african trypanosomes is influenced by innate protective molecules in the blood of primates. a subfraction of human high-density lipoprotein (hdl) containing apolipoprotein a-i, apolipoprotein l-i, and haptoglobin-related protein is toxic to trypanosoma brucei brucei but not the human sleeping sickness parasite trypanosoma brucei rhodesiense. it is thought that t. b. rhodesiense evolved from a t. b. brucei-like ancestor and expresses a defense protein that ablates the antitrypan ... | 2006 | 16896212 |
| hemizygous subtelomeres of an african trypanosome chromosome may account for over 75% of chromosome length. | african trypanosomes are parasitic protozoa that infect a wide range of mammals, including humans. these parasites remain extracellular in the mammalian bloodstream, where antigenic variation allows them to survive the immune response. the trypanosoma brucei nuclear genome sequence has been published recently. however, the significant chromosome size polymorphism observed among strains and subspecies of t. brucei, where total dna content may vary up to 30%, necessitates a comparative study to de ... | 2006 | 16899654 |
| switching trypanosome coats: what's in the wardrobe? | the african trypanosome trypanosoma brucei is best known for its extraordinarily sophisticated antigenic variation of a protective variant surface glycoprotein (vsg) coat. t. brucei has >1000 vsg genes and pseudogenes, of which one is transcribed at a time from one of multiple telomeric vsg expression sites. switching the active vsg gene can involve dna rearrangements replacing the old vsg with a new one, or alternatively transcriptional control. the astonishing revelation from the t. brucei gen ... | 2006 | 16908087 |
| roles for the trypanosoma brucei p2 transporter in db75 uptake and resistance. | a novel trypanocide, 2,5-bis(4-amidinophenyl)furan (db75), in its prodrug amidoxime-derivative form, 2,5-bis(4-amidinophenyl)furan-bis-o-methylamidoxime (db289), is in trials as the first orally administered drug for human african trypanosomiasis. db75 is a diamidine. resistance to some diamidines correlates to loss of uptake via the p2 aminopurine transporter. we show here that uptake of db75 into trypanosoma brucei also occurs principally via the p2 transporter. uptake of tritiated db75 occurr ... | 2006 | 16912218 |
| selenium metabolism in trypanosoma: characterization of selenoproteomes and identification of a kinetoplastida-specific selenoprotein. | proteins containing the 21st amino acid selenocysteine (sec) are present in the three domains of life. however, within lower eukaryotes, particularly parasitic protists, the dependence on the trace element selenium is variable as many organisms lost the ability to utilize sec. herein, we analyzed the genomes of trypanosoma and leishmania for the presence of genes coding for sec-containing proteins. the selenoproteomes of these flagellated protozoa have three selenoproteins, including distant hom ... | 2006 | 16914442 |
| rnai interference of xpo1 and sm genes and their effect on the spliced leader rna in trypanosoma brucei. | in trypanosomes, trans-splicing is a major essential rna-processing mechanism that involves the addition of a spliced leader sequence to all mrnas from a small rna species, known as the spliced leader rna (sl rna). sl rna maturation is poorly understood and it is not clear where assembly with sm proteins takes place. in this study, we followed the localization of the sl rna during knockdown of sm proteins and xpo1, which in metazoa functions in transport of mrna and u snrnas from the nucleus to ... | 2006 | 16916550 |
| selective di- or trimethylation of histone h3 lysine 76 by two dot1 homologs is important for cell cycle regulation in trypanosoma brucei. | dot1 is an evolutionarily conserved histone h3 lysine 79 (h3k79) methyltransferase. k79 methylation is associated with transcriptional activation, meiotic checkpoint control, and dna double-strand break (dsb) responses. trypanosoma brucei has two homologs, dot1a and dot1b, which are responsible for dimethylation and trimethylation of h3k76, respectively (k76 in t. brucei is synonymous to k79 in other organisms). k76 dimethylation is only detectable during mitosis, whereas trimethylation occurs t ... | 2006 | 16916638 |
| trypanosome alternative oxidase: from molecule to function. | trypanosome alternative oxidase (tao) is the cytochrome-independent terminal oxidase of the mitochondrial electron transport chain. tao is a diiron protein that transfers electrons from ubiquinol to oxygen, reducing the oxygen to water. the mammalian bloodstream forms of trypanosoma brucei depend solely on tao for respiration. the inhibition of tao by salicylhydroxamic acid (sham) or ascofuranone is trypanocidal. tao is present at a reduced level in the procyclic form of t. brucei, where it is e ... | 2006 | 16920028 |
| adaptations in the lipid metabolism of the protozoan parasite trypanosoma brucei. | trypanosomes are unicellular parasites and like all decent parasites, they try to obtain from the host as much material as possible, including lipids. however, the needs of a parasite are not always the same as those of the host, and therefore, mostly, some biosynthetic work still has to be done by the parasite itself. very often at least modifications of the lipid components that are acquired from the host have to be made. furthermore, next to the lipids trypanosoma brucei indeed obtains from t ... | 2006 | 16920110 |
| avant garde fatty acid synthesis by trypanosomes. | in this issue of cell, lee et al. (2006) report that the parasite trypanosoma brucei synthesizes fatty acids in an unconventional way. t. brucei and two other trypanosomes use enzymes called elongases to synthesize myristate, a fourteen carbon (c14) fatty acid essential for pathogenesis. this is an unexpected finding as these enzymes were thought only to elongate already long (c16 or c18) acyl chains. | 2006 | 16923380 |
| fatty acid synthesis by elongases in trypanosomes. | all eukaryotic and prokaryotic organisms are thought to synthesize fatty acids using a type i or type ii synthase. in addition, eukaryotes extend pre-existing long chain fatty acids using microsomal elongases (elos). we have found that trypanosoma brucei, a eukaryotic human parasite that causes sleeping sickness, uses three elongases instead of type i or type ii synthases for the synthesis of nearly all its fatty acids. trypanosomes encounter diverse environments during their life cycle with dif ... | 2006 | 16923389 |
| crystal structures of t. brucei mrp1/mrp2 guide-rna binding complex reveal rna matchmaking mechanism. | the mitochondrial rna binding proteins mrp1 and mrp2 form a heteromeric complex that functions in kinetoplastid rna editing. in this process, mrp1/mrp2 serves as a matchmaker by binding to guide rnas and facilitating their hybridization with cognate preedited mrnas. to understand the mechanism by which this complex performs rna matchmaking, we determined structures of trypanosoma brucei apomrp1/mrp2 and an mrp1/mrp2-grna complex. the structures show that mrp1/mrp2 is a heterotetramer and, despit ... | 2006 | 16923390 |
| the procyclin-associated genes of trypanosoma brucei are not essential for cyclical transmission by tsetse. | ep and gpeet procyclins are the major surface glycoproteins of trypanosoma brucei in the midgut of tsetse flies (glossina spp.). the procyclin genes are located at the beginning of polycistronic transcription units and are followed by at least one procyclin-associated gene (pag). the ep/pag1 locus on one copy of chromosome x begins with the three genes ep1, ep2 and pag1; the end of this unit has not been characterized previously. the ep/pag2 locus on the other copy of chromosome x contains the s ... | 2006 | 16930740 |
| combined contribution of tbat1 and tbmrpa to drug resistance in trypanosoma brucei. | | 2006 | 16935360 |
| aberrant receptor-mediated endocytosis of schistosoma mansoni glycoproteins on host lipoproteins. | bilharzia is one of the major parasitic infections affecting the public health and socioeconomic circumstances in (sub) tropical areas. its causative agents are schistosomes. since these worms remain in their host for decades, they have developed mechanisms to evade or resist the immune system. like several other parasites, their surface membranes are coated with a protective layer of glycoproteins that are anchored by a lipid modification. | 2006 | 16942390 |
| parasitology: peculiar lipid production. | | 2006 | 16943828 |
| trypanosoma brucei udp-galactose-4'-epimerase in ternary complex with nad+ and the substrate analogue udp-4-deoxy-4-fluoro-alpha-d-galactose. | the structure of the nad-dependent oxidoreductase udp-galactose-4'-epimerase from trypanosoma brucei in complex with cofactor and the substrate analogue udp-4-deoxy-4-fluoro-alpha-d-galactose has been determined using diffraction data to 2.7 a resolution. despite the high level of sequence and structure conservation between the trypanosomatid enzyme and those from humans, yeast and bacteria, the binding of the 4-fluoro-alpha-d-galactose moiety is distinct from previously reported structures. of ... | 2006 | 16946458 |
| the invariant surface glycoprotein isg75 gene family consists of two main groups in the trypanozoon subgenus. | in trypanosoma brucei brucei, an invariant surface glycoprotein of molecular weight 75 kda (isg75) is uniformly distributed over the surface of a trypanosome and is specific for bloodstream-form parasites. for the other taxa of the trypanozoon subgenus no data about this surface molecule are available. therefore, we investigated the isg75 in the genomes of several pathogenic trypanozoon by southern blot, pcr and rt-pcr and sequence analysis. this study reveals that (i) all members of the trypano ... | 2006 | 16948872 |
| okadaic acid overcomes the blocked cell cycle caused by depleting cdc2-related kinases in trypanosoma brucei. | mitosis and cytokinesis are highly coordinated in eukaryotic cells. but procyclic-form trypanosoma brucei under g1 or mitotic arrest is still capable of dividing, resulting in anucleate daughter cells (zoids). okadaic acid (oka), an inhibitor of protein phosphatases pp1 and pp2a, is known to inhibit kinetoplast replication and cell division yielding multinucleate cells with single kinetoplasts. however, when oka was applied to cells arrested in g1 or g2/m phase via rnai knockdown of specific cdc ... | 2006 | 16949574 |
| synthesis of oxysterols and nitrogenous sterols with antileishmanial and trypanocidal activities. | two sterol families have been synthesized: the first one is nitrogenous sterols containing amino, n-hydroxyimino or cyano group and the second one is oxysterols such as ketosterol and hydroxysterols. these compounds were then evaluated in vitro against leishmania donovani promastigotes and trypanosoma brucei brucei trypomastigotes. the most active compounds against l. donovani promastigotes were 7beta-aminomethylcholesterol and 7alpha,beta-aminocholesterol (ic50 in a range from 1 to 3 microm, pe ... | 2006 | 16949702 |
| sexual reproduction and the evolution of microbial pathogens. | three common systemic human fungal pathogens--cryptococcus neoformans, candida albicans and aspergillus fumigatus--have retained all the machinery to engage in sexual reproduction, and yet their populations are often clonal with limited evidence for recombination. striking parallels have emerged with four protozoan parasites that infect humans: toxoplasma gondii, trypanosoma brucei, trypanosoma cruzi and plasmodium falciparum. limiting sexual reproduction appears to be a common virulence strateg ... | 2006 | 16950098 |
| trypanosome ift mutants provide insight into the motor location for mobility of the flagella connector and flagellar membrane formation. | the flagella connector (fc) of procyclic trypanosomes is a mobile, transmembrane junction important in providing cytotactic morphogenetic information to the daughter cell. quantitative analyses of fc positioning along the old flagellum, involving direct observations and use of the mpm2 anti-phosphoprotein monoclonal reveals a ;stop point' is reached on the old flagellum which correlates well with the initiation of basal body migration and kinetoplast segregation. this demonstrates further comple ... | 2006 | 16954145 |
| tsetse fly saliva accelerates the onset of trypanosoma brucei infection in a mouse model associated with a reduced host inflammatory response. | tsetse flies (glossina sp.) are the vectors that transmit african trypanosomes, protozoan parasites that cause human sleeping sickness and veterinary infections in the african continent. these blood-feeding dipteran insects deposit saliva at the feeding site that enables the blood-feeding process. here we demonstrate that tsetse fly saliva also accelerates the onset of a trypanosoma brucei infection. this effect was associated with a reduced inflammatory reaction at the site of infection initiat ... | 2006 | 16954393 |
| procyclic trypanosoma brucei expresses separate sialidase and trans-sialidase enzymes on its surface membrane. | the procyclic stage of trypanosoma brucei in the insect vector expresses a surface-bound trans-sialidase (tbts) that transfers sialic acid from glycoconjugates in the environment to glycosylphosphatidylinositol-anchored proteins on its surface membrane. rna interference against tbts abolished trans-sialidase activity in procyclic cells but did not diminish sialidase activity, suggesting the presence of a separate sialidase enzyme for hydrolyzing sialic acid. a search of the t. brucei genome sequ ... | 2006 | 16956887 |
| biochemical characterization of trypanosoma brucei rna polymerase ii. | in trypanosoma brucei, transcription by rna polymerase ii accounts for the expression of the spliced leader (sl) rna and most protein coding mrnas. to understand the regulation of rna polymerase ii transcription in these parasites, we have purified a transcriptionally active enzyme through affinity chromatography of its essential subunit, rpb4. the enzyme preparation is active in both promoter-independent and promoter-dependent in vitro transcription assays. importantly, the enzyme is sensitive ... | 2006 | 16962183 |
| identification of novel inhibitors of udp-glc 4'-epimerase, a validated drug target for african sleeping sickness. | novel inhibitors of trypanosoma brucei and mammalian udp-glc 4'-epimerase were identified by screening a small library of natural products and commercially available drug-like molecules. the inhibitors possess low micromolar potency against the t. brucei and human enzymes in vitro, display a degree of selectivity between the two enzymes, and are cytotoxic to cultured t. brucei and mammalian cells. | 2006 | 16962325 |
| reconstitution of full-round uridine-deletion rna editing with three recombinant proteins. | uridine (u)-insertion/deletion rna editing in trypanosome mitochondria involves an initial cleavage of the preedited mrna at specific sites determined by the annealing of partially complementary guide rnas. an involvement of two rnase iii-containing core editing complex (l-complex) proteins, mp90 (krepb1) and mp61 (krepb3) in, respectively, u-deletion and u-insertion editing, has been suggested, but these putative enzymes have not been characterized or expressed in active form. recombinant mp90 ... | 2006 | 16963561 |
| chromosome-wide analysis of gene function by rna interference in the african trypanosome. | trypanosomatids of the order kinetoplastida are major contributors to global disease and morbidity, and understanding their basic biology coupled with the development of new drug targets represents a critical need. additionally, trypanosomes are among the more accessible divergent eukaryote experimental systems. the genome of trypanosoma brucei contains 8,131 predicted open reading frames (orfs), of which over half have no known homologues beyond the kinetoplastida and a substantial number of ot ... | 2006 | 16963636 |
| structure and reactivity of trypanosoma brucei pteridine reductase: inhibition by the archetypal antifolate methotrexate. | the protozoan trypanosoma brucei has a functional pteridine reductase (tbptr1), an nadph-dependent short-chain reductase that participates in the salvage of pterins, which are essential for parasite growth. ptr1 displays broad-spectrum activity with pterins and folates, provides a metabolic bypass for inhibition of the trypanosomatid dihydrofolate reductase and therefore compromises the use of antifolates for treatment of trypanosomiasis. catalytic properties of recombinant tbptr1 and inhibition ... | 2006 | 16968221 |
| sm core variation in spliceosomal small nuclear ribonucleoproteins from trypanosoma brucei. | messenger rna processing in trypanosomes by cis and trans splicing requires spliceosomal small nuclear ribonucleoproteins (snrnps) u1, u2, u4/u6, and u5, as well as the spliced leader (sl) rnp. as in other eukaryotes, these rnps share a core structure of seven sm polypeptides. here, we report that the identity of the sm protein constituents varies between spliceosomal snrnps: specifically, two of the canonical sm proteins, smb and smd3, are replaced in the u2 snrnp by two novel, u2 snrnp-specifi ... | 2006 | 16977313 |
| the pathogenesis of anaemia in goats experimentally infected with trypanosoma congolense or trypanosoma brucei: use of the myeloid:erythroid ratio. | the present study examined the development of anaemia in small east african goats experimentally infected with trypanosoma congolense or trypanosoma brucei. experimental goats received a primary trypanosome challenge on day 0, treated with diminazene aceturate on day 49 and received a secondary trypanosome challenge on day 77 of the 136-day experiment. both primary and secondary challenges were characterised by reduced peripheral erythrocyte counts, fall in packed cell volume (pcv), hypohaemoglo ... | 2007 | 16982150 |
| toward a rational design of selective multi-trypanosomatid inhibitors: a computational docking study. | compound v7, a benzothiazole which was recently found as selective inhibitor of trypanosomal tims, was docked into tims from trypanosoma cruzi, trypanosoma brucei, entamoeba histolytica, plasmodium falciparum, yeast, and human. structural analyses revealed the importance of the accessibility to the two aromatic clusters located at the dimer's interface for the selective inhibition of trypanosomal tims. thus, it was found that different accessibilities of the protein interface of tims plays an im ... | 2006 | 16997551 |
| blood-brain barrier traversal by african trypanosomes requires calcium signaling induced by parasite cysteine protease. | in this study we investigated why bloodstream forms of trypanosoma brucei gambiense cross human brain microvascular endothelial cells (bmecs), a human blood-brain barrier (bbb) model system, at much greater efficiency than do t. b. brucei. after noting that t. b. gambiense displayed higher levels of cathepsin l-like cysteine proteases, we investigated whether these enzymes contribute to parasite crossing. first, we found that t. b. gambiense crossing of human bmecs was abrogated by n-methylpiper ... | 2006 | 16998589 |
| using fragment cocktail crystallography to assist inhibitor design of trypanosoma brucei nucleoside 2-deoxyribosyltransferase. | the 1.8 a resolution de novo structure of nucleoside 2-deoxyribosyltransferase (ec 2.4.2.6) from trypanosoma brucei (tbndrt) has been determined by sada phasing in an unliganded state and several ligand-bound states. this enzyme is important in the salvage pathway of nucleoside recycling. to identify novel lead compounds, we exploited "fragment cocktail soaks". out of 304 compounds tried in 31 cocktails, four compounds could be identified crystallographically in the active site. in addition, we ... | 2006 | 17004709 |
| alternative editing of cytochrome c oxidase iii mrna in trypanosome mitochondria generates protein diversity. | trypanosomes use rna editing to produce most functional mitochondrial messenger rna. precise insertion and deletion of hundreds of uridines is necessary to make full-length cytochrome c oxidase iii (coxiii) mrna. we show that coxiii mrna can be alternatively edited by a mechanism using an alternative guide rna to make a stable mrna. this alternatively edited mrna is translated to produce a unique protein that fractionates with mitochondrial membranes and colocalizes with mitochondrial proteins i ... | 2006 | 17008930 |
| evidence for a sliding-resistance at the tip of the trypanosome flagellum. | motility in trypanosomes is achieved through the undulating behaviour of a single "9 + 2" flagellum; normally the flagellar waves begin at the flagellar tip and propagate towards the base. for flagella in general, however, propagation is from base-to-tip and it is believed that bend formation, and sustained regular oscillation, depend upon a localised resistance to inter-doublet sliding - which is normally conferred by structures at the flagellar base, typically the basal body. we therefore pred ... | 2006 | 17009329 |
| post-transcriptional control of nuclear-encoded cytochrome oxidase subunits in trypanosoma brucei: evidence for genome-wide conservation of life-cycle stage-specific regulatory elements. | trypanosomes represent an excellent model for the post-transcriptional regulation of gene expression because their genome is organized into polycistronic transcription units. however, few signals governing developmental stage-specific expression have been identified, with there being no compelling evidence for widespread conservation of regulatory motifs. as a tool to search for common regulatory sequences we have used the nuclear-encoded components of the cytochrome oxidase (cox) complex of the ... | 2006 | 17012283 |
| vector competence of glossina palpalis gambiensis for trypanosoma brucei s.l. and genetic diversity of the symbiont sodalis glossinidius. | tsetse flies transmit african trypanosomes, responsible for sleeping sickness in humans and nagana in animals. this disease affects many people with considerable impact on public health and economy in sub-saharan africa, whereas trypanosomes' resistance to drugs is rising. the symbiont sodalis glossinidius is considered to play a role in the ability of the fly to acquire trypanosomes. different species of glossina were shown to harbor genetically distinct populations of s. glossinidius. we there ... | 2007 | 17012373 |
| the thiol-based redox networks of pathogens: unexploited targets in the search for new drugs. | hydroperoxide metabolism in diverse pathogens is reviewed under consideration of involved enzymes as potential drug targets. the common denominator of the peroxidase systems of trypanosoma, leishmania, plasmodium, and mycobacterium species is the use of nad(p)h to reduce hydroperoxides including peroxynitrite via a flavin-containing disulfide reductase, a thioredoxin (trx)-related protein and a peroxidase that operates with thiol catalysis. in plasmodium falciparum, thioredoxin- and glutathione ... | 2006 | 17012768 |
| identification of a tryptophan-like epitope borne by the variable surface glycoprotein (vsg) of african trypanosomes. | antibodies (ab) directed against a tryptophan-like epitope (we) were previously detected in patients with human african trypanosomiasis (hat). we investigated whether or not these ab resulted from immunization against trypanosome antigen(s) expressing a we. by western blotting, we identified an antigen having an apparent molecular weight ranging from 60 to 65 kda, recognized by purified rabbit anti-we ab. this antigen, present in trypomastigote forms, was absent in procyclic forms and trypanosom ... | 2007 | 17014849 |
| programmed cell death in african trypanosomes. | until recently it had generally been assumed that apoptosis and other forms of programmed cell death evolved during evolution of the metazoans to regulate growth and development in these multicellular organisms. however, recent research is adding strength to the original phenotypic observations described almost a decade ago which indicated that some parasitic protozoa may have evolved a cell death pathway analogous to the process described as apoptosis in metazoa. here we explore the implication ... | 2006 | 17018168 |
| metabolic functions of glycosomes in trypanosomatids. | protozoan kinetoplastida, including the pathogenic trypanosomatids of the genera trypanosoma and leishmania, compartmentalize several important metabolic systems in their peroxisomes which are designated glycosomes. the enzymatic content of these organelles may vary considerably during the life-cycle of most trypanosomatid parasites which often are transmitted between their mammalian hosts by insects. the glycosomes of the trypanosoma brucei form living in the mammalian bloodstream display the h ... | 2006 | 17023066 |
| cofactor-independent phosphoglycerate mutase is an essential gene in procyclic form trypanosoma brucei. | glycolysis and gluconeogenesis are, in part, driven by the interconversion of 3- and 2-phosphoglycerate (3-pg and 2-pg) which is performed by phosphoglycerate mutases (pgams) which can be cofactor dependant (dpgam) or cofactor independent (ipgam). the african trypanosome, trypanosoma brucei, possesses the ipgam form which is thought to play an important role in glycolysis. here, we report on the use of rna interference to down-regulate the t. brucei ipgam in procyclic form t. brucei and evaluati ... | 2007 | 17024352 |
| functional characterization of a 48 kda trypanosoma brucei cap 2 rna methyltransferase. | kinetoplastid mrnas possess a unique hypermethylated cap 4 structure derived from the standard m7gpppn cap structure, with 2'-o methylations on the first four ribose sugars and additional base methylations on the first adenine and the fourth uracil. while the enzymes responsible for m7gpppn cap 0 formations has been characterized in trypanosoma brucei, the mechanism of cap 4 methylation and the role of the hypermethylated structure remain unclear. here, we describe the characterization of a 48 k ... | 2006 | 17028101 |
| activity of a second trypanosoma brucei hexokinase is controlled by an 18-amino-acid c-terminal tail. | trypanosoma brucei expresses two hexokinases that are 98% identical, namely, tbhk1 and tbhk2. homozygous null tbhk2-/- procyclic-form parasites exhibit an increased doubling time, a change in cell morphology, and, surprisingly, a twofold increase in cellular hexokinase activity. recombinant tbhk1 enzymatic activity is similar to that of other hexokinases, with apparent km values for glucose and atp of 0.09 +/- 0.02 mm and 0.28 +/- 0.1 mm, respectively. the k(cat) value for tbhk1 is 2.9 x 10(4) m ... | 2006 | 17028241 |
| gpi-anchored proteins and free gpi glycolipids of procyclic form trypanosoma brucei are nonessential for growth, are required for colonization of the tsetse fly, and are not the only components of the surface coat. | the procyclic form of trypanosoma brucei exists in the midgut of the tsetse fly. the current model of its surface glycocalyx is an array of rod-like procyclin glycoproteins with glycosylphosphatidylinositol (gpi) anchors carrying sialylated poly-n-acetyllactosamine side chains interspersed with smaller sialylated poly-n-acetyllactosamine-containing free gpi glycolipids. mutants for tbgpi12, deficient in the second step of gpi biosynthesis, were devoid of cell surface procyclins and poly-n-acetyl ... | 2006 | 17035628 |
| depletion of the thioredoxin homologue tryparedoxin impairs antioxidative defence in african trypanosomes. | in trypanosomes, the thioredoxin-type protein txn (tryparedoxin) is a multi-purpose oxidoreductase that is involved in the detoxification of hydroperoxides, the synthesis of dna precursors and the replication of the kinetoplastid dna. african trypanosomes possess two isoforms that are localized in the cytosol and in the mitochondrion of the parasites respectively. here we report on the biological significance of the ctxn (cytosolic txn) of trypanosoma brucei for hydroperoxide detoxification. dep ... | 2007 | 17040206 |
| protein tyrosine phosphatase tbptp1: a molecular switch controlling life cycle differentiation in trypanosomes. | differentiation in african trypanosomes (trypanosoma brucei) entails passage between a mammalian host, where parasites exist as a proliferative slender form or a g0-arrested stumpy form, and the tsetse fly. stumpy forms arise at the peak of each parasitaemia and are committed to differentiation to procyclic forms that inhabit the tsetse midgut. we have identified a protein tyrosine phosphatase (tbptp1) that inhibits trypanosome differentiation. consistent with a tyrosine phosphatase, recombinant ... | 2006 | 17043136 |
| identification and stage-specific association with the translational apparatus of tbzfp3, a ccch protein that promotes trypanosome life-cycle development. | the post-transcriptional control of gene expression is becoming increasingly important in the understanding of regulated events in eukaryotic cells. the parasitic kinetoplastids have a unique reliance on such processes, because their genome is organized into polycistronic transcription units in which adjacent genes are not coordinately regulated. indeed, the number of rna-binding proteins predicted to be encoded in the genome of kinetoplastids is unusually large, invoking the presence of unique ... | 2006 | 17043361 |
| evolution of tubulin gene arrays in trypanosomatid parasites: genomic restructuring in leishmania. | alpha- and beta-tubulin are fundamental components of the eukaryotic cytoskeleton and cell division machinery. while overall tubulin expression is carefully controlled, most eukaryotes express multiple tubulin genes in specific regulatory or developmental contexts. the genomes of the human parasites trypanosoma brucei and leishmania major reveal that these unicellular kinetoplastids possess arrays of tandem-duplicated tubulin genes, but with differences in organisation. while l. major possesses ... | 2006 | 17044946 |
| on the significance of host antibody response to the trypanosoma brucei transferrin receptor during chronic infection. | the transferrin (tf) receptor of trypanosoma brucei (tbtfr) is encoded by two expression-site-associated genes, esag6 and esag7. there are around 20 different expression sites containing different copies of these genes that encode tbtfrs with quite distinct affinities for tf of various hosts. it was proposed that t. brucei has developed multiple expression sites encoding different tbtfrs to ensure sufficient iron uptake in the presence of antibodies competing for binding to tf. here it is shown ... | 2006 | 17045507 |
| functional analysis of trypanosoma brucei puf1. | the genomes of trypanosoma brucei, leishmania major and trypanosoma cruzi each encode 10 proteins with puf domains. puf domain proteins from yeast and metazoa have been shown to bind rna and to regulate mrna stability and translation. phylogenetic analysis suggested that the puf proteins were duplicated and diverged early in evolution, and that most puf proteins were lost during the evolution of mammals. depletion of any of the first nine t. brucei puf protein mrnas by rna interference had no ef ... | 2006 | 17052765 |
| an unusual dicer-like1 protein fuels the rna interference pathway in trypanosoma brucei. | rna interference (rnai) is an evolutionarily conserved gene-silencing pathway that is triggered by double-stranded rna (dsrna). central to this pathway are two ribonucleases: dicer, a multidomain rnase iii family enzyme that initiates rnai by generating small interfering rnas (sirnas), and argonaute or slicer, an rnase h signature enzyme that affects cleavage of mrna. previous studies in the early diverging protozoan trypanosoma brucei have established a key role for argonaute 1 in rnai. however ... | 2006 | 17053086 |
| consequences of telomere shortening at an active vsg expression site in telomerase-deficient trypanosoma brucei. | trypanosoma brucei evades the host immune response by sequential expression of a large family of variant surface glycoproteins (vsg) from one of approximately 20 subtelomeric expression sites (es). vsg transcription is monoallelic, and little is known about the regulation of antigenic switching. to explore whether telomere length could affect antigenic switching, we created a telomerase-deficient cell line, in which telomeres shortened at a rate of 3 to 6 bp at each cell division. upon reaching ... | 2006 | 17071826 |
| roles of a trypanosoma brucei 5'->3' exoribonuclease homolog in mrna degradation. | the genome of the kinetoplastid parasite trypanosoma brucei encodes four homologs of the saccharomyces cerevisiae 5'-->3' exoribonucleases xrn1p and xrn2p/rat1p, xrna, xrnb, xrnc, and xrnd. in s. cerevisiae, xrn1p is a cytosolic enzyme involved in degradation of mrna, whereas xrn2p is involved in rna processing in the nucleus. trypanosome xrnd was found in the nucleus, xrnb and xrnc were found in the cytoplasm, and xrna appeared to be in both compartments. xrnd and xrna were essential for parasi ... | 2006 | 17077271 |
| galactose starvation in a bloodstream form trypanosoma brucei udp-glucose 4'-epimerase conditional null mutant. | galactose metabolism is essential for the survival of trypanosoma brucei, the etiological agent of african sleeping sickness. t. brucei hexose transporters are unable to transport galactose, which is instead obtained through the epimerization of udp-glucose to udp-galactose catalyzed by udp-glucose 4'-epimerase (gale). here, we have characterized the phenotype of a bloodstream form t. brucei gale conditional null mutant under nonpermissive conditions that induced galactose starvation. cellular l ... | 2006 | 17093269 |
| experimental african trypanosomiasis: lack of effective cd1d-restricted antigen presentation. | balb/c mice are highly susceptible to african trypanosomiasis, whereas c57bl/6 mice are relatively resistant. other investigators have reported that the synthesis of igg antibodies to purified membrane form of variant surface glycoprotein (mfvsg) of trypanosoma brucei is cd1 restricted. in this study, we examine the role of the cd1d/nkt cell pathway in susceptibility and resistance of mice to infection by african trypanosomes. administration of anti-cd1d antibodies to trypanosoma congolense-infe ... | 2006 | 17096643 |
| characterization of protein kinase ck2 from trypanosoma brucei. | ck2 is a ubiquitous but enigmatic kinase. the difficulty in assigning a role to ck2 centers on the fact that, to date, no biologically relevant modulator of its function has been identified. one common theme revolves around a constellation of known substrates involved in growth control, compatible with its concentration in the nucleus and nucleolus. we had previously described the identification of two catalytic subunits of ck2 in trypanosoma brucei and characterized one of them. here we report ... | 2007 | 17097160 |
| in trypanosoma brucei rna editing, tbmp18 (band vii) is critical for editosome integrity and for both insertional and deletional cleavages. | in trypanosome rna editing, uridylate (u) residues are inserted and deleted at numerous sites within mitochondrial pre-mrnas by an approximately 20s protein complex that catalyzes cycles of cleavage, u addition/u removal, and ligation. we used rna interference to deplete tbmp18 (band vii), the last unexamined major protein of our purified editing complex, showing it is essential. tbmp18 is critical for the u-deletional and u-insertional cleavages and for integrity of the approximately 20s editin ... | 2007 | 17101787 |
| identification of novel snrna-specific sm proteins that bind selectively to u2 and u4 snrnas in trypanosoma brucei. | in eukaryotes the seven sm core proteins bind to u1, u2, u4, and u5 snrnas. in trypanosoma brucei, sm proteins have been implicated in binding both spliced leader (sl) and u snrnas. in this study, we examined the function of these sm proteins using rnai silencing and protein purification. rnai silencing of each of the seven sm genes resulted in accumulation of sl rna as well as reduction of several u snrnas. interestingly, u2 was unaffected by the loss of smb, and both u2 and u4 snrnas were unaf ... | 2007 | 17105994 |
| interstrain sequence comparison, transcript map and clonal genomic rearrangement of a 28 kb locus on chromosome 9 of trypanosoma brucei. | | 2007 | 17112605 |
| mitochondrial fragmentation in apoptosis. | mitochondrial outer membrane permeabilization (momp) is associated with most pro-apoptotic stimuli. momp results in the release of cytochrome c from the mitochondria into the cytosol, triggering caspase activation and subsequent apoptosis. several theories explaining the mechanisms of momp have been proposed, one of which suggests that momp relies on the activation of the molecular machinery involved in fission, resulting in mitochondrial fragmentation. by contrast, several recent studies sugges ... | 2007 | 17116393 |
| the subcellular localisation of trypanosome rrp6 and its association with the exosome. | the exosome, a complex of 3'-exoribonucleases and associated proteins, is involved in the degradation of eukaryotic mrnas in the cytoplasm, and has rna processing and quality control functions in the nucleus. in yeast, the nuclear exosome differs from the cytoplasmic one in that it contains an additional non-essential component, rrp6p. in contrast, a small proportion of human rrp6 has been shown to localise to the cytoplasm as well. when we purified the trypanosoma brucei exosome from cytosolic ... | 2007 | 17118470 |
| kiss: the kinetoplastid rna editing sequence search tool. | kinetoplastid mitochondrial mrna editing is a post-transcriptional process of uridine insertion and deletion. editing is mediated by small rna molecules termed guide rnas (grnas). most grnas are encoded by numerous small circular dna minicircles, while the protein coding mitochondrial genes are encoded on a separate, larger genome called the maxicircle. in order to provide a workbench for the analysis of rna editing in kinetoplastids and a well-annotated set of guide rnas for trypanosoma brucei, ... | 2007 | 17123956 |
| novel inhibitors of the trypanosome alternative oxidase inhibit trypanosoma brucei brucei growth and respiration. | african trypanosomiasis is a deadly disease for which few chemotherapeutic options are available. the causative agents, trypanosoma brucei rhodesiense and t. b. gambiense, utilize a non-cytochrome, alternative oxidase (aox) for their cellular respiration. the absence of this enzyme in mammalian cells makes it a logical target for therapeutic agents. we designed three novel compounds, acb41, acd15, and acd16, and investigated their effects on trypanosome alternative oxidase (tao) enzymatic activi ... | 2006 | 17126803 |
| cholesterol import fails to prevent catalyst-based inhibition of ergosterol synthesis and cell proliferation of trypanosoma brucei. | trypanosoma brucei (tb) cultured in rat blood, bovine serum, or lipid-depleted serum generated distinct differences in cholesterol availability. whereas cell proliferation of the parasite was relatively unaffected by cholesterol availability, the ratios of cellular ergostenols to cholesterol varied from close to unity to 3 orders of magnitude different with cholesterol as the major sterol (>99%) of bloodstream form cells. in the procyclic form cultured with lipid-depleted serum, 15 sterols at 52 ... | 2007 | 17127773 |
| targeting of toxic compounds to the trypanosome's interior. | drugs can be targeted into african trypanosomes by exploiting carrier proteins at the surface of these parasites. this has been clearly demonstrated in the case of the melamine-based arsenical and the diamidine classes of drug that are already in use in the treatment of human african trypanosomiasis. these drugs can enter via an aminopurine transporter, termed p2, encoded by the tbat1 gene. other toxic compounds have also been designed to enter via this transporter. some of these compounds enter ... | 2006 | 17134653 |
| genetic exchange in trypanosoma brucei: evidence for mating prior to metacyclic stage development. | | 2007 | 17134768 |
| structure of the glycosylphosphatidylinositol anchor of the trypanosoma brucei transferrin receptor. | | 2007 | 17140675 |
| a 10 base-pair sequence within domain iii of the gpeet procyclin promoter is essential for the autonomous replication of a plasmid in procyclic trypanosoma brucei. | | 2007 | 17140676 |
| trypanosoma brucei brucei: biochemical characterization of ecto-nucleoside triphosphate diphosphohydrolase activities. | in this work we describe the ability of living cells of trypanosoma brucei brucei to hydrolyze extracellular atp. in these intact parasites there was a low level of atp hydrolysis in the absence of any divalent metal (4.72+/-0.51 nmol pi x 10(-7) cells x h(-1)). the atp hydrolysis was stimulated by mgcl(2) and the mg-dependent ecto-atpase activity was 27.15+/-2.91 nmol pi x 10(-7) cells x h(-1). this stimulatory activity was also observed when mgcl(2) was replaced by mncl(2). cacl(2) and zncl(2) ... | 2007 | 17141762 |
| in vitro antiprotozoal activities and cytotoxicity of some selected cameroonian medicinal plants. | eight extracts from seven selected cameroonian medicinal plants, traditionally used to treat malaria and other protozoal diseases, were tested in vitro for their antiprotozoal activities against plasmodium falciparum k1 chloroquine-resistant strain, leishmania donovani, trypanosoma cruzi and trypanosoma brucei rhodesiense, protozoa responsible for malaria, visceral leishmaniasis, chagas disease and african trypanosomiasis, respectively. the most active extract against plasmodium falciparum k1 st ... | 2007 | 17141994 |
| hydrolysis products of camp analogs cause transformation of trypanosoma brucei from slender to stumpy-like forms. | african sleeping sickness is a disease caused by trypanosoma brucei. t. brucei proliferate rapidly in the mammalian bloodstream as long, slender forms, but at higher population densities they transform into nondividing, short, stumpy forms. this is thought to be a mechanism adopted by t. brucei to establish a stable host-parasite relationship and to allow a transition into the insect stage of its life cycle. earlier studies have suggested a role for camp in mediating this transformation. in this ... | 2006 | 17142316 |
| deletion of the trypanosoma brucei superoxide dismutase gene sodb1 increases sensitivity to nifurtimox and benznidazole. | it has been more than 25 years since it was first reported that nifurtimox and benznidazole promote superoxide production in trypanosomes. however, there has been no direct evidence of an association between the drug-induced free radicals and trypanocidal activity. here, we identify a superoxide dismutase required to protect trypanosoma brucei from drug-generated superoxide. | 2007 | 17145786 |
| bisphosphonate inhibition of phosphoglycerate kinase: quantitative structure-activity relationship and pharmacophore modeling investigation. | we report the results of a three-dimensional quantitative structure-activity relationship (3d-qsar) and pharmacophore modeling investigation of the interaction of the enzyme 3-phosphoglycerate kinase (pgk) with aryl and alkyl bisphosphonates. for the human enzyme, the ic50 values are predicted within a factor of 2 over the 240x experimental range in activity, while for the yeast enzyme, binding of the more flexible alkyl bisphosphonates is predicted within a factor of approximately 4 (over a 250 ... | 2006 | 17154500 |
| substrate determinants for rna editing and editing complex interactions at a site for full-round u insertion. | multisubunit rna editing complexes catalyze uridylate insertion/deletion rna editing directed by complementary guide rnas (grnas). editing in trypanosome mitochondria is transcript-specific and developmentally controlled, but the molecular mechanisms of substrate specificity remain unknown. here we used a minimal a6 pre-mrna/grna substrate to define functional determinants for full-round insertion and editing complex interactions at the editing site 2 (es2). editing begins with pre-mrna cleavage ... | 2007 | 17158098 |
| telomere structure and function in trypanosomes: a proposal. | telomeres are specialized dna-protein complexes that stabilize chromosome ends, protecting them from nucleolytic degradation and illegitimate recombination. telomeres form a heterochromatic structure that can suppress the transcription of adjacent genes. these structures might have additional roles in trypanosoma brucei, as the major surface antigens of this parasite are expressed during its infectious stages from subtelomeric loci. we propose that the telomere protein complexes of trypanosomes ... | 2007 | 17160000 |
| mitochondrial fatty acid synthesis in trypanosoma brucei. | whereas other organisms utilize type i or type ii synthases to make fatty acids, trypanosomatid parasites such as trypanosoma brucei are unique in their use of a microsomal elongase pathway (elo) for de novo fatty acid synthesis (fas). because of the unusual lipid metabolism of the trypanosome, it was important to study a second fas pathway predicted by the genome to be a type ii synthase. we localized this pathway to the mitochondrion, and rna interference (rnai) or genomic deletion of acyl car ... | 2007 | 17166831 |
| the trypanosoma brucei camp phosphodiesterases tbrpdeb1 and tbrpdeb2: flagellar enzymes that are essential for parasite virulence. | cyclic nucleotide specific phosphodiesterases (pdes) are pivotal regulators of cellular signaling. they are also important drug targets. besides catalytic activity and substrate specificity, their subcellular localization and interaction with other cell components are also functionally important. in contrast to the mammalian pdes, the significance of pdes in protozoal pathogens remains mostly unknown. the genome of trypanosoma brucei, the causative agent of human sleeping sickness, codes for fiv ... | 2007 | 17167070 |
| kinetoplastid ppef phosphatases: dual acylated proteins expressed in the endomembrane system of leishmania. | bioinformatic analyses have been used to identify potential downstream targets of the essential enzyme n-myristoyl transferase in the tritryp species, leishmania major, trypanosoma brucei and trypanosoma cruzi. these database searches predict approximately 60 putative n-myristoylated proteins with high confidence, including both previously characterised and novel molecules. one of the latter is an n-myristoylated protein phosphatase which has high sequence similarity to the protein phosphatase w ... | 2007 | 17169445 |
| trypanosoma brucei arf1 plays a central role in endocytosis and golgi-lysosome trafficking. | the adp ribosylation factor (arf)1 orthologue in the divergent eukaryote trypanosoma brucei (tb) shares characteristics with both arf1 and arf6 and has a vital role in intracellular protein trafficking. tbarf1 is golgi localized in trypanosomes but associates with the plasma membrane when expressed in human cells. depletion of tbarf1 by rna interference causes a major decrease in endocytosis, which correlates with rab5 dissociation from early endosomes. although the golgi remains intact, parasit ... | 2007 | 17182848 |
| molecular interactions underlying the unusually high adenosine affinity of a novel trypanosoma brucei nucleoside transporter. | trypanosoma brucei encodes a relatively high number of genes of the equilibrative nucleoside transporter (ent) family. we report here the cloning and in-depth characterization of one t. brucei brucei ent member, tbnt9/at-d. this transporter was expressed in saccharomyces cerevisiae and displayed a uniquely high affinity for adenosine (km = 0.068 +/- 0.013 microm), as well as broader selectivity for other purine nucleosides in the low micromolar range, but was not inhibited by nucleobases or pyri ... | 2007 | 17185380 |
| regulated expression of glycosomal phosphoglycerate kinase in trypanosoma brucei. | in trypanosoma brucei, the pgkb and pgkc genes-encoding phosphoglycerate kinase are co-transcribed as part of a polycistronic rna. pgkb mrna and the cytosolic pgkb protein are much more abundant in the procyclic life-cycle stage than in bloodstream forms, whereas pgkc mrna and glycosomal pgkc protein are specific to bloodstream forms. we here show that a sequence between nucleotides 558 and 779 in the 3'-untranslated region of the pgkc mrna causes low expression of the chloramphenicol acetyltran ... | 2007 | 17187872 |
| characterization of glycosomal ring finger proteins of trypanosomatids. | the glycosomes of trypanosomatids are essential organelles that are evolutionarily related to peroxisomes of other eukaryotes. the peroxisomal ring proteins-pex2, pex10 and pex12-comprise a network of integral membrane proteins that function in the matrix protein import cycle. here, we describe pex10 and pex12 in trypanosoma brucei, leishmania major, and trypanosoma cruzi. we expressed gfp fusions of each t. brucei coding region in procyclic form t. brucei, where they localized to glycosomes and ... | 2007 | 17188680 |
| utp-bound and apo structures of a minimal rna uridylyltransferase. | 3'-uridylylation of rna is emerging as a phylogenetically widespread phenomenon involved in processing events as diverse as uridine insertion/deletion rna editing in mitochondria of trypanosomes and small nuclear rna (snrna) maturation in humans. this reaction is catalyzed by terminal uridylyltransferases (tutases), which are template-independent rna nucleotidyltransferases that specifically recognize utp and belong to a large enzyme superfamily typified by dna polymerase beta. multiple tutases, ... | 2007 | 17189640 |
| human trypanosoma evansi infection linked to a lack of apolipoprotein l-i. | humans have innate immunity against trypanosoma brucei brucei that is known to involve apolipoprotein l-i (apol1). recently, a case of t. evansi infection in a human was identified in india. we investigated whether the apol1 pathway was involved in this occurrence. the serum of the infected patient was found to have no trypanolytic activity, and the finding was linked to the lack of apol1, which was due to frameshift mutations in both apol1 alleles. trypanolytic activity was restored by the addi ... | 2006 | 17192540 |
| evidence for u-tail stabilization of grna/mrna interactions in kinetoplastid rna editing. | the most dramatic example of rna editing is found in the mitochondria of trypanosomes. in these organisms, u-insertions/deletions can create mrnas that are twice as large as the gene that encodes them. guide rnas (grnas) that are complementary to short stretches of the mature message direct the precise placements of the u residues. the binding of grna to mrna is a fundamental step in rna editing and understanding the relative importance of the elements that confer affinity and specificity on thi ... | 2004 | 17194935 |
| metabolic control analysis to identify optimal drug targets. | this chapter describes the basic principles of metabolic control analysis (mca) which is a quantitative methodology to evaluate the importance and relative contribution of individual metabolic steps in the overall functioning of a particular system. the control on the flux through a metabolic pathway or subsystem can be quantified by the control coefficients of the individual enzymes or components which reflects the extent to which the component is rate-limiting. the perturbation of an individua ... | 2007 | 17195475 |
| mechanism of translation based on intersubunit complementarities of ribosomal rnas and trnas. | a universal rule is found about nucleotide sequence complementarities between the regions 2653-2666 in the gtpase-binding site of 23s rrna and 1064-1077 of 16s rrna as well as between the region 1103-1107 of 16s rrna and guucg (or guuca) of trnas. this rule holds for all species in the living kingdoms except for two protista mitochondrial rrnas of trypanosoma brucei and plasmodium falciparum. we found that quite similar relationships for the two species hold under the assumption presented in the ... | 2007 | 17196221 |
| three dimensional structure and implications for the catalytic mechanism of 6-phosphogluconolactonase from trypanosoma brucei. | enzymes from the pentose phosphate pathway (ppp) are potential drug targets for the development of new drugs against trypanosoma brucei, the causative agent of african sleeping disease: for instance, the 6-phosphogluconate dehydrogenase is currently studied actively for such purposes. structural and functional studies are necessary to better characterize the associated enzymes and compare them to their human homologues, in order to undertake structure-based drug design studies on such targets. i ... | 2007 | 17196981 |
| high-throughput screening affords novel and selective trypanothione reductase inhibitors with anti-trypanosomal activity. | trypanothione reductase (tr), an enzyme that buffers oxidative stress in trypanosomatid parasites, was screened against commercial libraries containing approximately 134,500 compounds. after secondary screening, four chemotypes were identified as screening positives with selectivity for tr over human glutathione reductase. thirteen compounds from these four chemotypes were purchased, and their in vitro activity against tr and trypanosoma brucei is described. | 2007 | 17197182 |
| the effect of starvation on the susceptibility of teneral and non-teneral tsetse flies to trypanosome infection. | transmission of vector-borne diseases depends largely on the ability of the insect vector to become infected with the parasite. in tsetse flies, newly emerged or teneral flies are considered the most likely to develop a mature, infective trypanosome infection. this was confirmed during experimental infections where laboratory-reared glossina morsitans morsitans westwood (diptera: glossinidae) were infected with trypanosoma congolense or t. brucei brucei. the ability of mature adult tsetse flies ... | 2006 | 17199750 |
| the first crystal structure of phosphofructokinase from a eukaryote: trypanosoma brucei. | the crystal structure of the atp-dependent phosphofructokinase (pfk) from trypanosoma brucei provides the first detailed description of a eukaryotic pfk, and enables comparisons to be made with the crystal structures of bacterial atp-dependent and ppi-dependent pfks. the structure reveals that two insertions (the 17-20 and 329-348 loops) that are characteristic of trypanosomatid pfks, but absent from bacterial and mammalian atp-dependent pfks, are located within and adjacent to the active site, ... | 2007 | 17207816 |
| nuclear repositioning of the vsg promoter during developmental silencing in trypanosoma brucei. | interphase nuclear repositioning of chromosomes has been implicated in the epigenetic regulation of rna polymerase (pol) ii transcription. however, little is known about the nuclear position-dependent regulation of rna pol i-transcribed loci. trypanosoma brucei is an excellent model system to address this question because its two main surface protein genes, procyclin and variant surface glycoprotein (vsg), are transcribed by pol i and undergo distinct transcriptional activation or downregulation ... | 2007 | 17210949 |