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Sarma AV Ramana Rao MH Sarma JA Nagaraj R Dutta AS Kunwar AC 《Journal of biochemical and biophysical methods》2002,51(1):27-45
Several cyclic analogues of renin inhibitors, based on Glu-D-Phe-Lys motif have been investigated by NMR spectroscopy and molecular dynamics calculations (MD). The 15 membered macrocycle, resulting from Glu and Lys side-chain cyclization, exhibits conformational preference. The structural evidence from NMR shows the presence of hydrogen bond between Lys NH and Glu side-chain carbonyl, resulting in a 10 membered pseudo beta-turn-like structure. The structure of the cyclic moiety is similar in all the peptides, which takes at least two conformations around Calpha-Cbeta in Glu side chain. The restrained MD calculations further support such observations and show that the macrocycle is fairly rigid, with two conformations about the Glu Calpha-Cbeta bond. The linear peptide appendages, which are essential for activity in cyclic peptides, show an extended structure in the beta-region of Ramchandran plot. These calculations also demonstrate that for the most active peptide, two major conformers each exist about the Calpha-CO bond of the Lys, D-Trp and Leu residues. In this peptide, the cyclic moiety presents a negatively charged surface formed due to the carbonyl oxygens, which are thus available to form hydrogen bonds with the receptor. The linear fragment presents further binding sites with a surface which has the hydrophobic side chains of D-Trp, Leu and D-Met on one side and carbonyls on the other side. 相似文献
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Non-marine diatoms occur in the Deccan Intertrappean beds (Upper Cretaceous) of Mohgaon-Kalan, Chhindwara District, Madhya Pradesh and Pisdura, Lameta Formation (Upper Cretaceous), Maharashtra, India. This represents the oldest record of non-marine diatoms yet reported and the oldest from the Indian subcontinent. The diatoms were recovered from thin sections of chert and dinosaur coprolites by random fracturing. Solitary forms are the most common but colonial filaments up to five cells were also observed. Based on the morphological characters, the diatoms are identified as Aulacoseira Thwaites. The Lower Cretaceous marine diatom genus Archepyrgus Gersonde and Harwood also resembles Aulacoseira in general morphological characters and it seems that Aulacoseira evolved from Archepyrgus and migrated to the non-marine realm. 相似文献
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The changes in the free amino acid (FAA) levels, the rate of efflux of FAAs from the perfused liver, and the activity of some enzymes related to amino acid metabolism such as glutamate dehydrogenase (GDH, both reductive amination and oxidative deamination), glutamine synthetase (GS), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) were studied in the liver of a freshwater air-breathing teleost, the walking catfish, Clarias batrachus, perfused with 5 and 10 mM NH(4)Cl. The level of the various non-essential FAAs increased significantly, with a total increase of about 150%, which was accompanied by a significant increase of both ammonia and urea-N in the perfused liver both with 5 and 10 mM NH(4)Cl. The rate of efflux of these non-essential FAAs from the perfused liver also increased significantly with a total increase of about 115% and 160% at 5 and 10 mM NH(4)Cl, respectively. The activity of the mentioned amino acid metabolism-related enzymes in the perfused liver also got stimulated, except for GDH in the ammonia forming direction and ALT, under a higher ammonia load. The activity (both tissue and specific) of GDH in the glutamate forming direction increased maximally, followed by AST and GS in a decreasing order. Owing to these physiological adaptive strategies related to amino acid metabolism along with the presence of a functional and regulatory urea cycle (reported earlier), it is believed that this catfish is able to survive in very high ambient ammonia or in the air or in the mud during habitat drying. 相似文献
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Replication of the mammalian genome occurs only once per cell cycle and is under strict spatiotemporal control. DNA synthesis first takes place in the inner nucleus and moves gradually to the area subjacent to the nuclear membrane as S-phase progresses. We found that proteasome inhibitors specifically reduce DNA synthesis from later replicating origins but not that from earlier replicating origins. When MG132 was added in mid S-phase and washed off in late S-phase, however, DNA synthesis resumed not at the nuclear periphery, where it was last seen, but back in the inner nucleus. Analysis of DNA from these cells showed that mid to late replicating genes were rereplicated resulting in the overreplication of DNA. Our results suggest the existence of proteasome-dependent mechanisms regulating the orderly progression of S-phase. The transient treatment of mid S-phase cells with MG132 resulted in overreplication of DNA providing an easy experimental method to perturb the "once per cell cycle" control of genome replication in mammalian cells. 相似文献
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Aims: A total of nine Listeria monocytogenes strains (seven serotypes) were studied to ascertain whether the non-steroidal anti-inflammatory drug diclofenac (Dc) used in combination with the conventional antilisterial antibiotic gentamicin (Gm) or ampicillin (Am) synergistically augments the efficacy of the antibiotic in vitro .
Methods and Results: The effect of combination was evaluated by the checkerboard method to obtain a fractional inhibitory concentration (FIC) index followed by kill curves. Dc was synergistic with Gm (FIC 0·37) and there was indifference with Am (FIC 1) against L. monocytogenes ATCC 51774. The magnitude of the differences between killing by a single agent and the combination observed at 24 h was significant ( P < 0·05) for Dc plus Gm but not Dc plus Am.
Conclusions: Thus, the ability of extended antibiotic therapy may be improved with the help of this synergistic drug pair in listeriosis.
Significance and Impact of the Study: Such findings may indicate parallel administration of anti-inflammatory and anti listeriosis drugs. 相似文献
Methods and Results: The effect of combination was evaluated by the checkerboard method to obtain a fractional inhibitory concentration (FIC) index followed by kill curves. Dc was synergistic with Gm (FIC 0·37) and there was indifference with Am (FIC 1) against L. monocytogenes ATCC 51774. The magnitude of the differences between killing by a single agent and the combination observed at 24 h was significant ( P < 0·05) for Dc plus Gm but not Dc plus Am.
Conclusions: Thus, the ability of extended antibiotic therapy may be improved with the help of this synergistic drug pair in listeriosis.
Significance and Impact of the Study: Such findings may indicate parallel administration of anti-inflammatory and anti listeriosis drugs. 相似文献
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Gundeep Kaur Supreet Singh Harpreet Singh Mrinalini Chawla Tanima Dutta Harsimran Kaur Kyle Bender W. A. Snedden Sanjay Kapoor Ashwani Pareek Prabhjeet Singh 《PloS one》2015,10(8)
Cyclophilins, which bind to immunosuppressant cyclosporin A (CsA), are ubiquitous proteins and constitute a multigene family in higher organisms. Several members of this family are reported to catalyze cis-trans isomerisation of the peptidyl-prolyl bond, which is a rate limiting step in protein folding. The physiological role of these proteins in plants, with few exceptions, is still a matter of speculation. Although Arabidopsis genome is predicted to contain 35 cyclophilin genes, biochemical characterization, imperative for understanding their cellular function(s), has been carried only for few of the members. The present study reports the biochemical characterization of an Arabidopsis cyclophilin, AtCyp19-3, which demonstrated that this protein is enzymatically active and possesses peptidyl-prolyl cis-trans isomerase (PPIase) activity that is specifically inhibited by CsA with an inhibition constant (Ki) of 18.75 nM. The PPIase activity of AtCyp19-3 was also sensitive to Cu2+, which covalently reacts with the sulfhydryl groups, implying redox regulation. Further, using calmodulin (CaM) gel overlay assays it was demonstrated that in vitro interaction of AtCyp19-3 with CaM is Ca2+-dependent, and CaM-binding domain is localized to 35–70 amino acid residues in the N-terminus. Bimolecular fluorescence complementation assays showed that AtCyp19-3 interacts with CaM in vivo also, thus, validating the in vitro observations. However, the PPIase activity of the Arabidopsis cyclophilin was not affected by CaM. The implications of these findings are discussed in the context of Ca2+ signaling and cyclophilin activity in Arabidopsis. 相似文献