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71.
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Abdul Aziz Ali Dhrubajyoti Gogoi Amrita K. Chaliha Alak K. Buragohain Priyanka Trivedi Prakash J. Saikia Praveen S. Gehlot Arvind Kumar Vinita Chaturvedi Diganta Sarma 《Bioorganic & medicinal chemistry letters》2017,27(16):3698-3703
A library of seventeen novel 1,2,3-triazole derivatives were efficiently synthesized in excellent yields by the popular ‘click chemistry’ approach and evaluated in vitro for their anti-tubercular activity against Mycobacterium tuberculosis H37Ra (ATCC 25177 strain). Among the series, six compounds exhibited significant activity with minimum inhibitory concentration (MIC) values ranging from 3.12 to 0.78 μg/mL and along with no significant cytotoxicity against MBMDMQs (mouse bone marrow derived macrophages). Molecular docking of the target compounds into the active site of DprE1 (Decaprenylphosphoryl-β-d-ribose-2′-epimerase) enzyme revealed noteworthy information on the plausible binding interactions. 相似文献
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Cadmium induces a heterogeneous and caspase-dependent apoptotic response in <Emphasis Type="Italic">Saccharomyces cerevisiae</Emphasis> 总被引:1,自引:0,他引:1
Nargund AM Avery SV Houghton JE 《Apoptosis : an international journal on programmed cell death》2008,13(6):811-821
The toxic metal cadmium is linked to a series of degenerative disorders in humans, in which Cd-induced programmed cell death
(apoptosis) may play a role. The yeast, Saccharomyces cerevisiae, provides a valuable model for elucidating apoptosis mechanisms, and this study extends that capability to Cd-induced apoptosis.
We demonstrate that S. cerevisiae undergoes a glucose-dependent, programmed cell death in response to low cadmium concentrations, which is initiated within
the first hour of Cd exposure. The response was associated with induction of the yeast caspase, Yca1p, and was abolished in
a yca1Δ mutant. Cadmium-dependent apoptosis was also suppressed in a gsh1Δ mutant, indicating a requirement for glutathione. Other apoptotic markers, including sub-G1 DNA fragmentation and hyper-polarization of mitochondrial membranes, were also evident among Cd-exposed cells. These responses
were not distributed uniformly throughout the cell population, but were restricted to a subset of cells. This apoptotic subpopulation
also exhibited markedly elevated levels of intracellular reactive oxygen species (ROS). The heightened ROS levels alone were
not sufficient to induce apoptosis. These findings highlight several new perspectives to the mechanism of Cd-dependent apoptosis
and its phenotypic heterogeneity, while opening up future analyses to the power of the yeast model system. 相似文献
76.
Sean D. Hooper Iain J. Anderson Amrita Pati Daniel Dalevi Konstantinos Mavromatis Nikos C. Kyrpides 《Nucleic acids research》2009,37(7):2096-2104
In order to simplify and meaningfully categorize large sets of protein sequence data, it is commonplace to cluster proteins based on the similarity of those sequences. However, it quickly becomes clear that the sequence flexibility allowed a given protein varies significantly among different protein families. The degree to which sequences are conserved not only differs for each protein family, but also is affected by the phylogenetic divergence of the source organisms. Clustering techniques that use similarity thresholds for protein families do not always allow for these variations and thus cannot be confidently used for applications such as automated annotation and phylogenetic profiling. In this work, we applied a spectral bipartitioning technique to all proteins from 53 archaeal genomes. Comparisons between different taxonomic levels allowed us to study the effects of phylogenetic distances on cluster structure. Likewise, by associating functional annotations and phenotypic metadata with each protein, we could compare our protein similarity clusters with both protein function and associated phenotype. Our clusters can be analyzed graphically and interactively online. 相似文献
77.
Clum A Tindall BJ Sikorski J Ivanova N Mavrommatis K Lucas S Glavina T Del Rio Nolan M Chen F Tice H Pitluck S Cheng JF Chertkov O Brettin T Han C Detter JC Kuske C Bruce D Goodwin L Ovchinikova G Pati A Mikhailova N Chen A Palaniappan K Land M Hauser L Chang YJ Jeffries CD Chain P Rohde M Göker M Bristow J Eisen JA Markowitz V Hugenholtz P Kyrpides NC Klenk HP Lapidus A 《Standards in genomic sciences》2009,1(3):308-316
Pirellula staleyi Schlesner and Hirsch 1987 is the type species of the genus Pirellula of the family Planctomycetaceae. Members of this pear- or teardrop-shaped bacterium show a clearly visible pointed attachment pole and can be distinguished from other Planctomycetes by a lack of true stalks. Strains closely related to the species have been isolated from fresh and brackish water, as well as from hypersaline lakes. Here we describe the features of this organism, together with the complete genome sequence and annotation. This is the first completed genome sequence of the order Planctomyces and only the second sequence from the phylum Planctobacteria/Planctomycetes. The 6,196,199 bp long genome with its 4773 protein-coding and 49 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project. 相似文献
78.
Pati A Sikorski J Nolan M Lapidus A Copeland A Glavina Del Rio T Lucas S Chen F Tice H Pitluck S Cheng JF Chertkov O Brettin T Han C Detter JC Kuske C Bruce D Goodwin L Chain P D'haeseleer P Chen A Palaniappan K Ivanova N Mavromatis K Mikhailova N Rohde M Tindall BJ Göker M Bristow J Eisen JA Markowitz V Hugenholtz P Kyrpides NC Klenk HP 《Standards in genomic sciences》2009,1(2):141-149
Saccharomonospora viridis (Schuurmans et al. 1956) Nonomurea and Ohara 1971 is the type species of the genus Saccharomonospora which belongs to the family Pseudonocardiaceae. S. viridis is of interest because it is a Gram-negative organism classified among the usually Gram-positive actinomycetes. Members of the species are frequently found in hot compost and hay, and its spores can cause farmer's lung disease, bagassosis, and humidifier fever. Strains of the species S. viridis have been found to metabolize the xenobiotic pentachlorophenol (PCP). The strain described in this study has been isolated from peat-bog in Ireland. Here we describe the features of this organism, together with the complete genome sequence, and annotation. This is the first complete genome sequence of the family Pseudonocardiaceae, and the 4,308,349 bp long single replicon genome with its 3906 protein-coding and 64 RNA genes is part of the Genomic Encyclopedia of Bacteria and Archaea project. 相似文献
79.
Labutti K Pukall R Steenblock K Glavina Del Rio T Tice H Copeland A Cheng JF Lucas S Chen F Nolan M Bruce D Goodwin L Pitluck S Ivanova N Mavromatis K Ovchinnikova G Pati A Chen A Palaniappan K Land M Hauser L Chang YJ Jeffries CD Chain P Saunders E Brettin T Detter JC Han C Göker M Bristow J Eisen JA Markowitz V Hugenholtz P Kyrpides NC Klenk HP Lapidus A 《Standards in genomic sciences》2009,1(2):159-165
Anaerococcus prevotii (Foubert and Douglas 1948) Ezaki et al. 2001 is the type species of the genus, and is of phylogenetic interest because of its arguable assignment to the provisionally arranged family 'Peptostreptococcaceae'. A. prevotii is an obligate anaerobic coccus, usually arranged in clumps or tetrads. The strain, whose genome is described here, was originally isolated from human plasma; other strains of the species were also isolated from clinical specimen. Here we describe the features of this organism, together with the complete genome sequence and annotation. This is the first completed genome sequence of a member of the genus. Next to Finegoldia magna, A. prevotii is only the second species from the family 'Peptostreptococcaceae' for which a complete genome sequence is described. The 1,998,633 bp long genome (chromosome and one plasmid) with its 1852 protein-coding and 61 RNA genes is a part of the Genomic Encyclopedia of Bacteria and Archaea project. 相似文献
80.
Lixin Mi Nanqin Gan Amrita Cheema Sivanesan Dakshanamurthy Xiantao Wang David C. H. Yang Fung-Lung Chung 《The Journal of biological chemistry》2009,284(25):17039-17051
Although it is conceivable that cancer preventive isothiocyanates (ITCs), a family of compounds in cruciferous vegetables, induce cell cycle arrest and apoptosis through a mechanism involving oxidative stress, our study shows that binding to cellular proteins correlates with their potencies of apoptosis induction. More recently, we showed that ITCs bind selectively to tubulins. The differential binding affinities toward tubulin among benzyl isothiocyanate, phenethyl isothiocyanate, and sulforaphane correlate well with their potencies of inducing tubulin conformation changes, microtubule depolymerization, and eventual cell cycle arrest and apoptosis in human lung cancer A549 cells. These results support that tubulin binding by ITCs is an early event for cell growth inhibition. Here we demonstrate that ITCs can selectively induce degradation of both α- and β-tubulins in a variety of human cancer cell lines in a dose- and time-dependent manner. The onset of degradation, a rapid and irreversible process, is initiated by tubulin aggregation, and the degradation is proteasome-dependent. Results indicate that the degradation is triggered by ITC binding to tubulin and is irrelevant to oxidative stress. This is the first report that tubulin, a stable and abundant cytoskeleton protein required for cell cycle progression, can be selectively degraded by a small molecule.Microtubules as a major cytoskeleton component in all eukaryotic cells play essential roles such as maintenance of cell polarity, intracellular traffic, organization, and cell motility (1–4). During cell division, the microtubule-formed mitotic spindle ensures the replicated chromosomes separate evenly at the end of the mitotic phase to the two daughter cells (1). It is because of its essential roles in cell growth that microtubules become a valid target for the development of anti-microtubule drugs against the rapidly growing cancer cells (2), as interference of microtubule dynamics arrests cell cycle progression and induces apoptosis (3). Therefore, microtubules have been considered one of the best targets to date for cancer chemotherapy (4).Isothiocyanates (ITCs)3 are among the best studied chemopreventive small molecules (5). The three most studied ITCs, including benzyl-ITC (BITC; abundant in garden cress), phenethyl-ITC (PEITC; in watercress), and sulforaphane (SFN; in broccoli sprouts), have been shown to induce apoptosis and cell cycle arrest (5–8). Although it is believed that oxidative stress plays a role in cell cycle arrest and apoptosis induced by ITCs (6–12), we found that binding to proteins is a predominant intracellular chemical reaction of ITCs, and their protein binding affinities correlate well with inhibition of cell proliferation and induction of apoptosis (13). Recently, we identified tubulin, the microtubule constituent, as an in vivo target of ITCs by two-dimensional gel electrophoresis and mass spectrometry (14). The growth inhibition of human non-small lung cancer A549 cells by ITCs followed the order of BITC > PEITC > SFN. The same order of potency was seen in their binding affinities toward tubulin, induction of its conformational changes, and inhibition of its polymerization. The study provides the first evidence of an in vivo ITC-tubulin binding adduct, indicating that direct modification of cysteines in tubulin by ITCs, rather than oxidative stress, may trigger cell cycle arrest and apoptosis.Here we report an unexpected novel finding that tubulin is selectively degraded in a variety of human cancer cells treated with ITCs. We provide evidence that the degradation is initiated by its binding with ITCs and mediated by the ubiquitin-proteasome pathway. Tubulin has long been viewed as a stable and abundant protein, and its levels in cells are tightly regulated (15). In the literature, the only studies on cellular tubulin level change are related to “the auto-regulation theory,” i.e. when microtubules collapse, the presence of a massive amount of tubulin monomers would selectively destabilize tubulin mRNA and subsequently decrease tubulin protein synthesis (16–18). To our knowledge, there is no report on tubulin degradation as a result of treatment with any agents. Our studies provide strong evidence that supports tubulin as a target of ITCs for cell growth inhibition, pointing to a new mechanism for the anti-microtubule or anti-mitosis effects of ITCs through covalent binding to tubulin and presenting a platform to study protein stability by modification with small molecules. 相似文献