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971.
Rishi Kishore Vishwakarma Krunal Arvind Patel Prashant Sonawane Somesh Singh Ruby Uma Kumari Dinesh Chandra Agrawal Bashir Mohammad Khan 《Bioinformation》2012,8(22):1075-1081
Farnesyl pyrophosphate synthase (FPS; EC 2.5.1.10) is a key enzyme in isoprenoid biosynthetic pathway and provides precursors
for the biosynthesis of various pharmaceutically important metabolites. It catalyzes head to tail condensation of two isopentenyl
pyrophosphate molecules with dimethylallyl pyrophosphate to form C15 compound farnesyl pyrophosphate. Recent studies have
confirmed FPS as a molecular target of bisphosphonates for drug development against bone diseases as well as pathogens.
Although large numbers of FPSs from different sources are known, very few protein structures have been reported till date. In the
present study, FPS gene from medicinal plant Bacopa monniera (BmFPS) was characterized by comparative modeling and docking.
Multiple sequence alignment showed two highly conserved aspartate rich motifs FARM and SARM (DDXXD). The 3-D model of
BmFPS was generated based on structurally resolved FPS crystal information of Gallus gallus. The generated models were validated
by various bioinformatics tools and the final model contained only α-helices and coils. Further, docking studies of modeled BmFPS
with substrates and inhibitors were performed to understand the protein ligand interactions. The two Asp residues from FARM
(Asp100 and Asp104) as well as Asp171, Lys197 and Lys262 were found to be important for catalytic activity. Interaction of
nitrogen containing bisphosphonates (risedronate, alendronate, zoledronate and pamidronate) with modeled BmFPS showed
competitive inhibition; where, apart from Asp (100, 104 and 171), Thr175 played an important role. The results presented here
could be useful for designing of mutants for isoprenoid biosynthetic pathway engineering well as more effective drugs against
osteoporosis and human pathogens.
Abbreviations
IPP - Isopentenyl Pyrophosphate, DMAPP - Dimethylallyl Pyrophosphate, GPP - Geranyl Pyrophosphate, FPP - FPPFarnesyl Pyrophosphate, DOPE - Discrete Optimized Protein Energy, BmFPS - Bacopa monniera Farnesyl Pyrophosphate Synthase, RMSD - Root Mean square Deviation, OPLS-AA - Optimized Potentials for Liquid Simulations- All Atom, FARM - First Aspartate Rich Motif, SARM - Second Aspartate Rich Motif. 相似文献972.
973.
Overcompensation of plants in response to herbivory and the by-product benefits of mutualism 总被引:6,自引:0,他引:6
Agrawal AA 《Trends in plant science》2000,5(7):309-313
Plants that overcompensate for herbivory are relatively healthier when damaged. In this mutualistic association, the herbivore benefits from the plant, and the plant benefits from the herbivore's actions. As long as the benefit to the plant outweighs the costs imposed by browsing herbivores, this interaction should remain stable. Many apparently parasitic associations can be mutually beneficial under some environmental conditions. 相似文献
974.
QSAR Study on tadpole narcosis 总被引:1,自引:0,他引:1
Agrawal VK Chaturvedi S Abraham MH Khadikar PV 《Bioorganic & medicinal chemistry》2003,11(20):4523-4533
975.
976.
Medicinal chemistry and therapeutic potential of CpG DNA 总被引:9,自引:0,他引:9
The observation that oligodeoxynucleotides containing CpG dinucleotides (CpG DNA) exhibit several immunological effects has led to their use as therapeutic agents and adjuvants for various diseases. Several CpG DNA drug candidates are currently being evaluated, either as monotherapies or as adjuvants (with vaccines, antibodies, antigens and allergens), in preclinical and clinical trials against cancers, viral and bacterial infections, allergies and asthma. Knowledge gained from studies of the medicinal chemistry of CpG DNA has provided a basis for designing a second generation of CpG DNA agents with desirable cytokine-inducing and potent immunomodulatory activity. This article reviews recent progress in understanding the effects of CpG DNA, the medicinal chemistry of CpG DNA, and its possible therapeutic applications. 相似文献
977.
P Balasubramanian JC Lang KR Jatana B Miller E Ozer M Old DE Schuller A Agrawal TN Teknos TA Summers MB Lustberg M Zborowski JJ Chalmers 《PloS one》2012,7(7):e42048
Epithelial to mesenchymal transition (EMT) has been hypothesized as a mechanism by which cells change phenotype during carcinogenesis, as well as tumor metastasis. Whether EMT is involved in cancer metastasis has a specific, practical impact on the field of circulating tumor cells (CTCs). Since the generally accepted definition of a CTC includes the expression of epithelial surface markers, such as EpCAM, if a cancer cell loses its epithelial surface markers (which is suggested in EMT), it will not be separated and/or identified as a CTC. We have developed, and previously reported on the use of, a purely negative enrichment technology enriching for CTCs in the blood of squamous cell carcinoma of the head and neck (SCCHN). This methodology does not depend on the expression of surface epithelial markers. Using this technology, our initial data on SCCHN patient blood indicates that the presence of CTCs correlates with worse disease-free survival. Since our enrichment is not dependent on epithelial markers, we have initiated investigation of the presence of mesenchymal markers in these CTC cells to include analysis of: vimentin, epidermal growth factor receptor, N-cadherin, and CD44. With the aid of confocal microscopy, we have demonstrated not only presumed CTCs that express and/or contain: a nucleus, cytokeratins, vimentin, and either EGFR, CD44, or N-cadherin, but also cells that contain all of the aforementioned proteins except cytokeratins, suggesting that the cells have undergone the EMT process. We suggest that our negative depletion enrichment methodology provides a more objective approach in identifying and evaluating CTCs, as opposed to positive selection approaches, as it is not subjective to a selection bias and can be tailored to accommodate a variety of cytoplasmic and surface markers which can be evaluated to identify a multitude of phenotypic patterns within CTCs from individual patients, including so-called EMT as presented here. 相似文献
978.
979.
980.
Vinay Shankar Veena Thekkeettil Gaurav Sharma Veena Agrawal 《In vitro cellular & developmental biology. Plant》2012,48(1):113-119
To evaluate the role of exogenous application of a phytochelating agent glutathione in increasing resistance against different
heavy metals stress, nodal explants excised from 28-day-old in vitro seedlings of Spilanthes calva L. were cultured on Murashige and Skoog’s medium supplemented with 10 μM benzyl adenine and five different concentrations
(1, 5, 50, 100, or 200 mg/l) of four heavy metals: As2O3, CuSO4, ZnSO4, or Pb(NO3)2. Data were recorded for percent survival, shoot number, and shoot length after 28 d of heavy metal treatment. All four heavy
metals severely inhibited growth and morphogenesis. Pb proved most inhibitory whereas Zn was least effective. Pb was further
selected to study the reversal effect of glutathione on morphogenesis. The addition of different concentrations (1, 5, 10,
or 25 mg/l) of glutathione to media containing the Pb resulted in a significant improvement in almost all growth parameters.
Inclusion of glutathione at 10 mg/l was optimum for maximum reversal of the negative effects of heavy metals on morphogenesis. 相似文献