Browsing by Author "Singh A."
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Item Effect of arsenate substitution on phosphate repository of cell: A computational study(Royal Society Publishing, 2018) Singh A.; Giri K.The structural analogy with phosphate derives arsenate into various metabolic processes associated with phosphate inside the organisms. But it is difficult to evaluate the effect of arsenate substitution on the stability of individual biological phosphate species, which span from a simpler monoester form like pyrophosphate to a more complex phosphodiester variant like DNA. In this study, we have classified the physiological phosphate esters into three different classes on the basis of their structural differences. This classification has helped us to present a concise theoretical study on the kinetic stability of phosphate analogue species of arsenate against hydrolysis. All the calculations have been carried out using QM/MM methods of our Own N-layer Integrated molecular Orbital molecular Mechanics (ONIOM). For quantum mechanical region, we have used M06-2X density functional with 6-31+G(2d,2p) basis set and for molecular mechanics we have used the AMBER force field. The calculated rate constants for hydrolysis show that none of the phosphate analogue species of arsenate has a reasonable stability against hydrolysis.Item Insights into the Molecular Mechanism of Arsenic Phytoremediation(Springer New York LLC, 2019) Thakur S.; Choudhary S.; Majeed A.; Singh A.; Bhardwaj P.Arsenic (As) is a widespread carcinogenic pollutant. Phytoremediation is the most suited technology for alleviating the As contamination of soil. In this review, we have discussed the uptake mechanism and the associated transporters for different As species. Glutathione, phytochelatins, metallothionins, and secondary metabolites play important role in As detoxification and enhancing tolerance. The roles of MAPK signaling and calcium signaling are highlighted in the perception of As stress along with phytohormones signaling in stress tolerance. Furthermore, transcription factors involved in regulation of gene expression under As stress are discussed. High-throughput sequencing has reduced the time duration and enhanced the knowledge regarding understanding the molecular mechanism of phytoremediation. The role of CRISPR/Cas9 and synthetic genes in context to phytoremediation is discussed. We have provided a holistic understanding of the present knowledge about phytoremediation in the context of mechanisms of the As uptake and tolerance. A complete understanding of the phytoremediation process is essential for As-risk mitigation and will help in augmenting its efficiency and true potential.Item RNAseq-based phylogenetic reconstruction of Taxaceae and Cephalotaxaceae(Blackwell Publishing Inc., 2019) Majeed A.; Singh A.; Choudhary S.; Bhardwaj P.Taxaceae and Cephalotaxaceae are the two economically important conifer families. Over the years there has been much controversy over the issue of merging these families. The position of Amentotaxus and Torreya is also ambiguous. Some authors consider them closer to Taxaceae while others deemed them to fit within Cephalotaxaceae. Still, others prefer to raise them to their own tribe. Different morphological, anatomical, embryological and phylogenetic evidence supports one or the other view, making the precise delineation between them unresolved. Here we used an RNAseq-based approach to obtain orthologous genes across the selected species to reconstruct a more robust phylogeny of these families. A total of 233.123 million raw reads were de novo assembled to generate nine different transcript assemblies for the corresponding species. Of the 940 191 assembled transcripts across nine species, we generated 409 734 unigenes, which were clustered into orthologous groups. A total of 331 single-copy complete orthologous groups were selected for phylogenetic analysis. Maximum-likelihood, maximum-parsimony and Bayesian phylogenetic trees showed a sister relationship between Taxaceae and Cephalotaxaceae. Our analysis supports their distinctiveness at the family level and also shows that Amentotaxus and Torreya fit within Cephalotaxaceae.Item Steering the antitumor drug discovery campaign towards structurally diverse indolines(Academic Press Inc., 2020) Thakur A.; Singh A.; Kaur N.; Ojha R.; Nepali K.Indoline framework is often perpended as a privileged heterocycle present in medicinally valuable compounds of natural and synthetic origin. This review article presents the rational approaches/strategies employed for the design of anticancer indolines along with the structure activity relationship and mechanistic insights revealed in the in-vitro and in-vivo assays. The chemist has always been fascinated towards the indoline ring for the construction of antitumor scaffolds owing to its versatility as evidenced by its existence in scaffolds inducing antiproliferative effects via diverse mechanisms. To the delight of medicinal chemist, the applicability of indoline has also been expanded towards the design of dual inhibitors (multitargeting anticancer agents) as well as PROTACS. Overall, it can be concluded that indoline moiety is a magic bullet and the scaffolds containing this ring are foraying towards detailed preclinical and clinical stage investigations by leaps and bounds.