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41.
Cassera MB Gozzo FC D'Alexandri FL Merino EF del Portillo HA Peres VJ Almeida IC Eberlin MN Wunderlich G Wiesner J Jomaa H Kimura EA Katzin AM 《The Journal of biological chemistry》2004,279(50):51749-51759
Two genes encoding the enzymes 1-deoxy-D-xylulose-5-phosphate synthase and 1-deoxy-D-xylulose-5-phosphate reductoisomerase have been recently identified, suggesting that isoprenoid biosynthesis in Plasmodium falciparum depends on the methylerythritol phosphate (MEP) pathway, and that fosmidomycin could inhibit the activity of 1-deoxy-D-xylulose-5-phosphate reductoisomerase. The metabolite 1-deoxy-D-xylulose-5-phosphate is not only an intermediate of the MEP pathway for the biosynthesis of isopentenyl diphosphate but is also involved in the biosynthesis of thiamin (vitamin B1) and pyridoxal (vitamin B6) in plants and many microorganisms. Herein we report the first isolation and characterization of most downstream intermediates of the MEP pathway in the three intraerythrocytic stages of P. falciparum. These include, 1-deoxy-D-xylulose-5-phosphate, 2-C-methyl-D-erythritol-4-phosphate, 4-(cytidine-5-diphospho)-2-C-methyl-D-erythritol, 4-(cytidine-5-diphospho)-2-C-methyl-D-erythritol-2-phosphate, and 2-C-methyl-D-erythritol-2,4-cyclodiphosphate. These intermediates were purified by HPLC and structurally characterized via biochemical and electrospray mass spectrometric analyses. We have also investigated the effect of fosmidomycin on the biosynthesis of each intermediate of this pathway and isoprenoid biosynthesis (dolichols and ubiquinones). For the first time, therefore, it is demonstrated that the MEP pathway is functionally active in all intraerythrocytic forms of P. falciparum, and de novo biosynthesis of pyridoxal in a protozoan is reported. Its absence in the human host makes both pathways very attractive as potential new targets for antimalarial drug development. 相似文献
42.
Distribution and conservation of mobile elements in the genus Drosophila 总被引:13,自引:1,他引:12
Essentially nothing is known of the origin, mode of transmission, and
evolution of mobile elements within the genus Drosophila. To better
understand the evolutionary history of these mobile elements, we examined
the distribution and conservation of homologues to the P, I, gypsy, copia,
and F elements in 34 Drosophila species from three subgenera. Probes
specific for each element were prepared from D. melanogaster and hybridized
to genomic DNA. Filters were washed under conditions of increasing
stringency to estimate the similarity between D. melanogaster sequences and
their homologues in other species. The I element homologues show the most
limited distribution of all elements tested, being restricted to the
melanogaster species group. The P elements are found in many members of the
subgenus Sophophora but, with the notable exception of D. nasuta, are not
found in the other two subgenera. Copia-, gypsy-, and F-element homologues
are widespread in the genus, but their similarity to the D. melanogaster
probe differs markedly between species. The distribution of copia and P
elements and the conservation of the gypsy and P elements is inconsistent
with a model that postulates a single ancient origin for each type of
element followed by mating-dependent transmission. The data can be
explained by horizontal transmission of mobile elements between
reproductively isolated species.
相似文献
43.
Sheran HW Law Rudolf SS Wu Patrick KS Ng Richard MK Yu Richard YC Kong 《BMC molecular biology》2006,7(1):15-13
Background
Hypoxia-inducible factors (HIFs) are involved in adaptive and survival responses to hypoxic stress in mammals. In fish, very little is known about the functions of HIFs. 相似文献44.
Yan Boucher Camilla L Nesbø Michael J Joss Andrew Robinson Bridget C Mabbutt Michael R Gillings WFord Doolittle HW Stokes 《BMC evolutionary biology》2006,6(1):3-14
Background
Integrons are genetic elements capable of the acquisition, rearrangement and expression of genes contained in gene cassettes. Gene cassettes generally consist of a promoterless gene associated with a recombination site known as a 59-base element (59-be). Multiple insertion events can lead to the assembly of large integron-associated cassette arrays. The most striking examples are found in Vibrio, where such cassette arrays are widespread and can range from 30 kb to 150 kb. Besides those found in completely sequenced genomes, no such array has yet been recovered in its entirety. We describe an approach to systematically isolate, sequence and annotate large integron gene cassette arrays from bacterial strains. 相似文献45.
YjeQ is a protein broadly conserved in bacteria containing an N-terminal oligonucleotide/oligosaccharide fold (OB-fold) domain, a central GTPase domain, and a C-terminal zinc-finger domain. YjeQ binds tightly and stoichiometrically to the 30S subunit, which stimulates its GTPase activity by 160-fold. Despite growing evidence for the involvement of the YjeQ protein in bacterial 30S subunit assembly, the specific function and mechanism of this protein remain unclear. Here, we report the costructure of YjeQ with the 30S subunit obtained by cryo-electron microscopy. The costructure revealed that YjeQ interacts simultaneously with helix 44, the head and the platform of the 30S subunit. This binding location of YjeQ in the 30S subunit suggests a chaperone role in processing of the 3' end of the rRNA as well as in mediating the correct orientation of the main domains of the 30S subunit. In addition, the YjeQ binding site partially overlaps with the interaction site of initiation factors 2 and 3, and upon binding, YjeQ covers three inter-subunit bridges that are important for the association of the 30S and 50S subunits. Hence, our structure suggests that YjeQ may assist in ribosome maturation by preventing premature formation of the translation initiation complex and association with the 50S subunit. Together, these results support a role for YjeQ in the late stages of 30S maturation. 相似文献
46.
Da-Chuan Cheng Christian Billich Shing-Hong Liu Horst Brunner Yi-Chen Qiu Yu-Lin Shen Hans Jürgen Brambs Arno Schmidt-Trucksäss Uwe HW Schütz 《Biomedical engineering online》2011,10(1):26
Background
Systematic aerobe training has positive effects on the compliance of dedicated arterial walls. The adaptations of the arterial structure and function are associated with the blood flow-induced changes of the wall shear stress which induced vascular remodelling via nitric oxide delivered from the endothelial cell. In order to assess functional changes of the common carotid artery over time in these processes, a precise measurement technique is necessary. Before this study, a reliable, precise, and quick method to perform this work is not present. 相似文献47.
Baumeister S Wiesner J Reichenberg A Hintz M Bietz S Harb OS Roos DS Kordes M Friesen J Matuschewski K Lingelbach K Jomaa H Seeber F 《PloS one》2011,6(5):e19334
Background
Highly charged compounds typically suffer from low membrane permeability and thus are generally regarded as sub-optimal drug candidates. Nonetheless, the highly charged drug fosmidomycin and its more active methyl-derivative have proven parasiticidal activity against erythrocytic stages of the malaria parasite Plasmodium falciparum. Both compounds target the isoprenoid biosynthesis pathway present in bacteria and plastid-bearing organisms, like apicomplexan parasites. Surprisingly, the compounds are inactive against a range of apicomplexans replicating in nucleated cells, including Toxoplasma gondii. FR900098Methodology/Principal Findings
Since non-infected erythrocytes are impermeable for FR90098, we hypothesized that these drugs are taken up only by erythrocytes infected with Plasmodium. We provide evidence that radiolabeled accumulates in theses cells as a consequence of parasite-induced new properties of the host cell, which coincide with an increased permeability of the erythrocyte membrane. Babesia divergens, a related parasite that also infects human erythrocytes and is also known to induce an increase in membrane permeability, displays a similar susceptibility and uptake behavior with regard to the drug. In contrast, Toxoplasma gondii-infected cells do apparently not take up the compounds, and the drugs are inactive against the liver stages of Plasmodium berghei, a mouse malaria parasite. FR900098Conclusions/Significance
Our findings provide an explanation for the observed differences in activity of fosmidomycin and against different Apicomplexa. These results have important implications for future screens aimed at finding new and safe molecular entities active against P. falciparum and related parasites. Our data provide further evidence that parasite-induced new permeability pathways may be exploited as routes for drug delivery. FR900098相似文献48.
Mohammed Yagoub Jomaa Muhammed Altaf Saeed Ahmad Gaurav Bhatia Jatinder Singh Saleh Altuwaijri Anvarhusein A. Isab 《Biometals》2017,30(5):787-795
Seven new platinum(II) complexes (1–7) of triethylphosphine (Et3P) and thiones (L) with general formula, cis-[Pt(Et3P)2(L)2]Cl2 were prepared and characterized by elemental analysis, FTIR and NMR (1H, 13C & 31P) measurements. The analytical and spectroscopic data suggested the formation of the desired complexes. The complexes were tested for in vitro cytotoxicity against four cell lines: Hela (human cervical adenocarcinoma), MCF-7 (human breast carcinoma), A549 (human lung carcinoma), and HTC15 (human colon carcinoma). The anticancer activity values of compounds 1–6 are much better than cisplatin and carboplatin as indicated by their IC50 values. 相似文献
49.
Wiesner J Mitsch A Jomaa H Schlitzer M 《Bioorganic & medicinal chemistry letters》2003,13(13):2159-2161
In a previous report, we have provided evidence that novel anti-malarial compounds based on 2,5-diaminobenzophenone farnesyltransferase inhibitors might benefit from the presence of a polar moiety at the para position of the terminal phenyl of the arylfurylacryloyl partial structure. Here, we demonstrate that different moieties with hydrogen bond acceptor properties lead to equipotent or even improved anti-malarial activity in comparison to the nitro group described before. 相似文献
50.