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Shubhandra Tripathi Akhil Kumar B. Sathish Kumar Arvind S. Negi 《Journal of biomolecular structure & dynamics》2016,34(6):1232-1240
Microtubule stabilizers provide an important mode of treatment via mitotic cell arrest of cancer cells. Recently, we reported two novel neolignans derivatives Cmp10 and Cmp19 showing anticancer activity and working as microtubule stabilizers at micromolar concentrations. In this study, we have explored the binding site, mode of binding, and stabilization by two novel microtubule stabilizers Cmp10 and Cmp19 using in silico molecular docking, molecular dynamics (MD) simulation, and binding free energy calculations. Molecular docking studies were performed to explore the β-tubulin binding site of Cmp10 and Cmp19. Further, MD simulations were used to probe the β-tubulin stabilization mechanism by Cmp10 and Cmp19. Binding affinity was also compared for Cmp10 and Cmp19 using binding free energy calculations. Our docking results revealed that both the compounds bind at Ptxl binding site in β-tubulin. MD simulation studies showed that Cmp10 and Cmp19 binding stabilizes M-loop (Phe272-Val288) residues of β-tubulin and prevent its dynamics, leading to a better packing between α and β subunits from adjacent tubulin dimers. In addition, His229, Ser280 and Gln281, and Arg278, Thr276, and Ser232 were found to be the key amino acid residues forming H-bonds with Cmp10 and Cmp19, respectively. Consequently, binding free energy calculations indicated that Cmp10 (?113.655 kJ/mol) had better binding compared to Cmp19 (?95.216 kJ/mol). This study provides useful insight for better understanding of the binding mechanism of Cmp10 and Cmp19 and will be helpful in designing novel microtubule stabilizers. 相似文献
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The effect ofl-ascorbic acid on the biosynthesis of aflatoxin inAspergillus parasiticus was studied. Ascorbic acid at lower concentrations did not inhibit the growth of fungus but markedly induced aflatoxin biosynthesis. At a concentration of 1000 ppm of ascorbic acid, 4.8-fold higher levels of aflatoxin were detected. Copper did not enhance the induction of toxin synthesis by ascorbic acid when added to the growth medium. Ascorbic acid at 1000 ppm was also found to induce aflatoxin synthesis in resting mycelia. Chloroform (1% vol/vol) was found to induce aflatoxin synthesis under similar conditions. Ascorbic acid in the presence of ferrous ion can cause lipid peroxidation, which in turn is responsible for the induction of aflatoxin synthesis. During the induction of aflatoxin synthesis by ascorbic acid, the uptake of carbon source (acetate) was not affected. This observation suggests that on ascorbic acid treatment a precursor or an intermediate of aflatoxin biosynthesis is synthesized in vivo and is responsible for the higher levels of toxin without increasing the uptake of acetate. 相似文献
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R. Kapila M. S. Negi P. This M. Delseny P. S. Srivastava M. Lakshmikumaran 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1996,93(7):1123-1129
The 459-bp HindIII (pBN-4) and the 1732-bp Eco RI (pBNE8) fragments from the Brassica nigra genome were cloned and shown to be members of a dispersed repeat family. Of the three major diploid Brassica species, the repeat pBN-4 was found to be highly specific for the B. nigra genome. The family also hybridized to Sinapis arvensis showing that B. nigra had a closer relationship with the S. arvensis genome than with B. oleracea or B. campestris. The clone pBNE8 showed homology to a number of tRNA species indicating that this family of repeats may have originated from a tRNA sequence. The species-specific 459-bp repeat pBN-4 was localized on the B. nigra chromosomes using monosomic addition lines. In addition to the localization of pBN-4, the chromosomal distribution of two other species-specific repeats, pBN34 and pBNBH35 (reported earlier), was studied. The dispersed repeats pBN-4 and pBNBH35 were found to be present on all of the chromosomes, whereas the tandem repeat pBN34 was localized on two chromosomes. 相似文献
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The responses of seedlings of three fast growing tree species,Eucalyptus hybrid(E. camaldulensis × E. teriticornis), Casuarina equisetifolia andMelia azedarach, to different levels of soil moisture in controlled glasshouse conditions were compared. The survival percentage, height of plants, number of leaves per plant, number of branches, fresh mass and dry mass of roots, stems, branches and leaves decreased in the three species with increasing water stress. Stomatal frequency and length of stomata inEucalyptus andMelia also decreased with increasing water stress. However, no significant difference was obtained in the width of stomata and the ratio of number of open stomata to total number of stomata per unit area. The leaf thickness decreased, but the thickness of palisade parenchyma increased with increasing water stress inEucalyptus hybrid andCasuarina. Leaf thickness ofMelia did not show any significant variation due to water stress. 相似文献
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Keratinolytic proteinase produced by Candida albicans 总被引:11,自引:0,他引:11
Candida albicans was cultivated in various media that contained human stratum corneum, human scalp hair or keratin powder (cow's hoof) as a nitrogen source. Production of a keratinolytic proteinase (KPase) was observed when C. albicans was incubated in the medium containing stratum corneum. However, there was no production of a KPase that could digest human stratum corneum in the medium containing hair or keratin powder. alpha-fibrous protein extracted from human stratum corneum was digested by the KPase. The pH optimum of the enzyme was 4.0 and enzyme activity was inhibited by pepstatin A and chymostatin. The KPase, a kind of carboxyl proteinase, may be important for C. albicans to enable it to play a pathogenic role in vivo. 相似文献
8.
Geetanjali Negi Anurag Sharma Manorama Dey Garvita Dhanawat Nagma Parveen 《Biophysical reviews》2022,14(5):1109
Attachment to and fusion with cell membranes are two major steps in the replication cycle of many human viruses. We focus on these steps for three enveloped viruses, i.e., HIV-1, IAVs, and SARS-CoV-2. Viral spike proteins drive the membrane attachment and fusion of these viruses. Dynamic interactions between the spike proteins and membrane receptors trigger their specific attachment to the plasma membrane of host cells. A single virion on cell membranes can engage in binding with multiple receptors of the same or different types. Such dynamic and multivalent binding of these viruses result in an optimal attachment strength which in turn leads to their cellular entry and membrane fusion. The latter process is driven by conformational changes of the spike proteins which are also class I fusion proteins, providing the energetics of membrane tethering, bending, and fusion. These viruses exploit cellular and membrane factors in regulating the conformation changes and membrane processes. Herein, we describe the major structural and functional features of spike proteins of the enveloped viruses including highlights on their structural dynamics. The review delves into some of the case studies in the literature discussing the findings on multivalent binding, membrane hemifusion, and fusion of these viruses. The focus is on applications of biophysical tools with an emphasis on single-particle methods for evaluating mechanisms of these processes at the molecular and cellular levels. 相似文献
9.
Chavan SS Huerta PT Robbiati S Valdes-Ferrer S Ochani M Dancho M Frankfurt M Volpe BT Tracey KJ Diamond B 《Molecular medicine (Cambridge, Mass.)》2012,18(9):930-937
Severe sepsis, a syndrome that complicates infection and injury, affects 750,000 annually in the United States. The acute mortality rate is approximately 30%, but, strikingly, sepsis survivors have a significant disability burden: up to 25% of survivors are cognitively and physically impaired. To investigate the mechanisms underlying persistent cognitive impairment in sepsis survivors, here we developed a murine model of severe sepsis survivors following cecal ligation and puncture (CLP) to study cognitive impairments. We observed that serum levels of high mobility group box 1 (HMGB1), a critical mediator of acute sepsis pathophysiology, are increased in sepsis survivors. Significantly, these levels remain elevated for at least 4 wks after CLP. Sepsis survivors develop significant, persistent impairments in learning and memory, and anatomic changes in the hippocampus associated with a loss of synaptic plasticity. Administration of neutralizing anti-HMGB1 antibody to survivors, beginning 1 wk after onset of peritonitis, significantly improved memory impairments and brain pathology. Administration of recombinant HMGB1 to na?ve mice recapitulated the memory impairments. Together, these findings indicate that elevated HMGB1 levels mediate cognitive decline in sepsis survivors, and suggest that it may be possible to prevent or reverse cognitive impairments in sepsis survivors by administration of anti-HMGB1 antibodies. 相似文献
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