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Debarati Paul Neha Rastogi Ulrich Krauss Michael Schlomann Gunjan Pandey Janmejay Pandey Anuradha Ghosh Rakesh K. Jain 《Indian journal of microbiology》2008,48(2):279-286
Ring hydroxylating dioxygenases (RHDOs) are one of the most important classes of enzymes featuring in the microbial metabolism
of several xenobiotic aromatic compounds. One such RHDO is benzenetriol dioxygenase (BtD) which constitutes the metabolic
machinery of microbial degradation of several mono- phenolic and biphenolic compounds including nitrophenols. Assessment of
the natural diversity of benzenetriol dioxygenase (btd) gene sequence is of great significance from basic as well as applied study point of view. In the present study we have evaluated
the gene sequence variations amongst the partial btd genes that were retrieved from microorganisms enriched for PNP degradation from pesticide contaminated agriculture soils.
The gene sequence analysis was also supplemented with an in silico restriction digestion analysis. Furthermore, a phylogenetic analysis based on the deduced amino acid sequence(s) was performed
wherein the evolutionary relatedness of BtD enzyme with similar aromatic dioxygenases was determined. The results obtained
in this study indicated that this enzyme has probably undergone evolutionary divergence which largely corroborated with the
taxonomic ranks of the host microorganisms. 相似文献
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Isabel Regadas Olle Dahlberg Roshan Vaid Oanh Ho Sergey Belikov Gunjan Dixit Sebastian Deindl Jiayu Wen Mattias Mannervik 《Molecular cell》2021,81(8):1766-1780.e10
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Sarika Gunjan Sunil Kumar Singh Tanuj Sharma Hemlata Dwivedi Bhavana Singh Chauhan Mohammad Imran Siddiqi Renu Tripathi 《Apoptosis : an international journal on programmed cell death》2016,21(9):955-964
Recent studies pioneer the existence of a novel programmed cell death pathway in malaria parasite plasmodium and suggest that it could be helpful in developing new targeted anti-malarial therapies. Considering this fact, we evaluated the underlying action mechanism of this pathway in mefloquine (MQ) treated parasite. Since cysteine proteases play a key role in apoptosis hence we performed preliminary computational simulations to determine binding affinity of MQ with metacaspase protein model. Binding pocket identified using computational studies, was docked with MQ to identify it’s potential to bind with the predicted protein model. We further determined apoptotic markers such as mitochondrial dysregulation, activation of cysteine proteases and in situ DNA fragmentation in MQ treated/untreated parasites by cell based assay. Our results showed low mitochondrial membrane potential, enhanced activity of cysteine protease and increased number of fragmented DNA in treated parasites compared to untreated ones. We next tested the involvement of oxidative stress in MQ mediated cell death and found significant increase in reactive oxygen species generation after 24 h of treatment. Therefore we conclude that apart from hemozoin inhibition, MQ is competent to induce apoptosis in plasmodium by activating metacaspase and ROS production. 相似文献
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Samuel Dagogo‐Jack Indira Umamaheswaran Hasan Askari Gunjan Tykodi 《Obesity (Silver Spring, Md.)》2003,11(2):232-237
Objective: To examine the effects of graded doses of hydrocortisone (HC) on leptin secretion, and determine the effect of fasting. Research Methods and Procedures: This was a randomized, placebo‐controlled, crossover study, with a 1‐week “washout” period between interventions. Eight healthy subjects [age = 36 ± 2.3 years (±SE), body mass index = 31.5 ± 1.6 kg/m2] completed the dose‐response study in which an intravenous infusion of saline (placebo) or HC (30 or 100 mg) was administered for 24 hours. Four healthy subjects (age = 35.2 ± 3.0 years, body mass index = 27.1 ± 2.1 kg/m2) completed the fasting study, which entailed continuous infusion of saline, HC (300 mg/24 hours) in the fed state, or HC (300 mg/24 hours) with total caloric deprivation for 24 hours. Blood sampling was performed every 1 to 2 hours for measurement of leptin, cortisol, insulin, and glucose levels. Results: Peak hyperleptinemia occurred after 16 hours of HC infusion; peak/baseline leptin levels were 129% (placebo), 140% (30 mg of HC for 24 hours, p = 0.05), and 185% (100 mg of HC for 24 hours, p < 0.01). During infusion of HC (300 mg/24 hours or placebo), the peak/baseline plasma leptin levels were 16.1 ± 5.8/12.8 ± 5.9 ng/mL (placebo with food, 126%), 14.6 ± 6.0/12.5 ± 6.5 ng/mL (HC fasting, 117%), and 32.5 ± 12.5/12.0 ± 8.4 ng/mL (HC with food, 271%, p < 0.001). Discussion: Leptin secretory responses occur at physiological doses of HC, are obliterated by fasting, and thus may be of metabolic significance. 相似文献
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Meetu Gupta Andaleeb Sajid Gunjan Arora Vibha Tandon Yogendra Singh 《The Journal of biological chemistry》2009,284(50):34723-34734
Mycobacterium tuberculosis profoundly exploits protein phosphorylation events carried out by serine/threonine protein kinases (STPKs) for its survival and pathogenicity. Forkhead-associated domains (FHA), the phosphorylation-responsive modules, have emerged as prominent players in STPK mediated signaling. In this study, we demonstrate the association of the previously uncharacterized FHA domain-containing protein Rv0019c with cognate STPK PknB. The consequent phosphorylation of Rv0019c is shown to be dependent on the conserved residues in the Rv0019c FHA domain and activation loop of PknB. Furthermore, by creating deletion mutants we identify Thr36 as the primary phosphorylation site in Rv0019c. During purification of Rv0019c from Escherichia coli, the E. coli protein chloramphenicol acetyltransferase (CAT) specifically and reproducibly copurifies with Rv0019c in a FHA domain-dependent manner. On the basis of structural similarity of E. coli CAT with M. tuberculosis PapA5, a protein involved in phthiocerol dimycocerosate biosynthesis, PapA5 is identified as an interaction partner of Rv0019c. The interaction studies on PapA5, purified as an unphosphorylated protein from E. coli, with Rv0019c deletion mutants reveal that the residues N-terminal to the functional FHA domain of Rv0019c are critical for formation of the Rv0019c-PapA5 complex and thus constitute a previously unidentified phosphoindependent binding motif. Finally, PapA5 is shown to be phosphorylated on threonine residue(s) by PknB, whereas serine/threonine phosphatase Mstp completely reverses the phosphorylation. Thus, our data provides initial clues for a possible regulation of PapA5 and hence the phthiocerol dimycocerosate biosynthesis by PknB, either by direct phosphorylation of PapA5 or indirectly through Rv0019c. 相似文献
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Sajid A Arora G Gupta M Singhal A Chakraborty K Nandicoori VK Singh Y 《Journal of bacteriology》2011,193(19):5347-5358
During protein synthesis, translation elongation factor Tu (Ef-Tu) is responsible for the selection and binding of the cognate aminoacyl-tRNA to the acceptor site on the ribosome. The activity of Ef-Tu is dependent on its interaction with GTP. Posttranslational modifications, such as phosphorylation, are known to regulate the activity of Ef-Tu in several prokaryotes. Although a study of the Mycobacterium tuberculosis phosphoproteome showed Ef-Tu to be phosphorylated, the role of phosphorylation in the regulation of Ef-Tu has not been studied. In this report, we show that phosphorylation of M. tuberculosis Ef-Tu (MtbEf-Tu) by PknB reduced its interaction with GTP, suggesting a concomitant reduction in the level of protein synthesis. Overexpression of PknB in Mycobacterium smegmatis indeed reduced the level of protein synthesis. MtbEf-Tu was found to be phosphorylated by PknB on multiple sites, including Thr118, which is required for optimal activity of the protein. We found that kirromycin, an Ef-Tu-specific antibiotic, had a significant effect on the nucleotide binding of unphosphorylated MtbEf-Tu but not on the phosphorylated protein. Our results show that the modulation of the MtbEf-Tu-GTP interaction by phosphorylation can have an impact on cellular protein synthesis and growth. These results also suggest that phosphorylation can change the sensitivity of the protein to the specific inhibitors. Thus, the efficacy of an inhibitor can also depend on the posttranslational modification(s) of the target and should be considered during the development of the molecule. 相似文献