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S-Adenosyl methionine

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https://www.readbyqxmd.com/read/27899265/discovery-of-novel-dna-methyltransferase-3a-inhibitors-via-structure-based-virtual-screening-and-biological-assays
#1
Zhiyuan Shao, Pan Xu, Wen Xu, Linjuan Li, Shien Liu, Rukang Zhang, Yu-Chih Liu, Chenhua Zhang, Shijie Chen, Cheng Luo
DNA methyltransferases are involved in diverse biological processes and abnormal methylation patterns play essential roles in cancer initiation and progression. DNA methyltransferase 3A (DNMT3A) acting as a de novo DNA methyltransferase, has gained widespread attention especially in haematological diseases. To date, large numbers of DNMTs inhibitors have been discovered, however, the small molecular inhibitors targeting DNMT3A are still in its infancy. In this study, structure-based virtual screening in combination with biological assays was performed to discovery potent novel DNMT3A inhibitors...
November 11, 2016: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/27881678/evolutionary-adaptation-of-the-essential-trna-methyltransferase-trmd-to-the-signaling-molecule-3-5-camp-in-bacteria
#2
Yong Zhang, Rym Agrebi, Lauren E Bellows, Jean-François Collet, Volkhard Kaever, Angelika Gründling
The nucleotide signaling molecule 3',5'-cyclic adenosine monophosphate (3',5'-cAMP) plays important physiological roles, ranging from carbon catabolite repression in bacteria to mediating the action of hormones in higher eukaryotes, including human. However, it remains unclear whether 3',5'-cAMP is universally present in the Firmicutes group of bacteria. We hypothesized that searching for proteins that bind 3',5'-cAMP might provide new insight into this question. Accordingly, we performed a genome-wide screen, and identified the essential Staphylococcus aureus tRNA m1G37 methyltransferase enzyme TrmD, which is conserved in all three domains of life, as a tight 3',5'-cAMP binding protein...
November 23, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27877178/an-s-adenosyl-methionine-synthetase-sams-gene-from-andropogon-virginicus-l-confers-aluminum-stress-tolerance-and-facilitates-epigenetic-gene-regulation-in-arabidopsis-thaliana
#3
Bunichi Ezaki, Aiko Higashi, Norie Nanba, Takumi Nishiuchi
Candidate clones which conferred Al tolerance to yeast transformants (TFs) were obtained from a cDNA library derived from a highly Al-tolerant poaceae, Andropogon virginicus L. One such clone, AL3A-4, encoded an S-adenosyl methionine synthetase (SAMS) gene. A full-length cDNA was obtained by 5'-RACE, designated AvSAMS1, and introduced into Arabidopsis thaliana to investigate its biological functions under Al stress. Two TF plant lines both showed higher tolerance than the Col-0 ecotype (non-TF) not only for Al stress, but also for Cu, Pb, Zn and diamide stresses, suggesting the AvSAMS1 was a multiple tolerance gene...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27834868/steric-clash-in-the-set-domain-of-histone-methyltransferase-nsd1-as-a-cause-of-sotos-syndrome-and-its-genetic-heterogeneity-in-a-brazilian-cohort
#4
Kyungsoo Ha, Priya Anand, Jennifer A Lee, Julie R Jones, Chong Ae Kim, Debora Romeo Bertola, Jonathan D J Labonne, Lawrence C Layman, Wolfgang Wenzel, Hyung-Goo Kim
Most histone methyltransferases (HMTase) harbor a predicted Su(var)3-9, Enhancer-of-zeste, Trithorax (SET) domain, which transfers a methyl group to a lysine residue in their substrates. Mutations of the SET domains were reported to cause intellectual disability syndromes such as Sotos, Weaver, or Kabuki syndromes. Sotos syndrome is an overgrowth syndrome with intellectual disability caused by haploinsufficiency of the nuclear receptor binding SET domain protein 1 (NSD1) gene, an HMTase at 5q35.2-35.3. Here, we analyzed NSD1 in 34 Brazilian Sotos patients and identified three novel and eight known mutations...
November 9, 2016: Genes
https://www.readbyqxmd.com/read/27834682/does-viperin-function-as-a-radical-s-adenosyl-l-methionine-dependent-enzyme-in-regulating-farnesylpyrophosphate-synthase-expression-and-activity
#5
Caitlyn Makins, Soumi Ghosh, Gabriel D Román-Meléndez, Paige A Malec, Robert T Kennedy, E Neil G Marsh
Viperin is an endoplasmic reticulum-associated antiviral responsive protein, which is highly up regulated in eukaryotic cells upon viral infection through both interferon-dependent and independent pathways. Viperin is predicted to be a radical S-adenosyl-L-methionine (SAM) enzyme, but it is unknown if viperin actually exploits radical SAM chemistry to exert its antiviral activity. We have investigated the interaction of viperin with its most firmly established cellular target, farnesyl pyrophosphate synthase (FPPS)...
November 10, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27827847/programmed-effects-in-neurobehavior-and-antioxidative-physiology-in-zebrafish-embryonically-exposed-to-cadmium-observations-and-hypothesized-adverse-outcome-pathway-framework
#6
Sander Ruiter, Josefine Sippel, Manon C Bouwmeester, Tobias Lommelaars, Piet Beekhof, Hennie M Hodemaekers, Frank Bakker, Evert-Jan van den Brandhof, Jeroen L A Pennings, Leo T M van der Ven
Non-communicable diseases (NCDs) are a major cause of premature mortality. Recent studies show that predispositions for NCDs may arise from early-life exposure to low concentrations of environmental contaminants. This developmental origins of health and disease (DOHaD) paradigm suggests that programming of an embryo can be disrupted, changing the homeostatic set point of biological functions. Epigenetic alterations are a possible underlying mechanism. Here, we investigated the DOHaD paradigm by exposing zebrafish to subtoxic concentrations of the ubiquitous contaminant cadmium during embryogenesis, followed by growth under normal conditions...
November 2, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27826850/dna-labeling-using-dna-methyltransferases
#7
Miglė Tomkuvienė, Edita Kriukienė, Saulius Klimašauskas
DNA methyltransferases (MTases) uniquely combine the ability to recognize and covalently modify specific target sequences in DNA using the ubiquitous cofactor S-adenosyl-L-methionine (AdoMet). Although DNA methylation plays important roles in biological signaling, the transferred methyl group is a poor reporter and is highly inert to further biocompatible derivatization. To unlock the biotechnological power of these enzymes, two major types of cofactor AdoMet analogs were developed that permit targeted MTase-directed attachment of larger moieties containing functional or reporter groups onto DNA...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27826849/engineering-and-directed-evolution-of-dna-methyltransferases
#8
Paola Laurino, Liat Rockah-Shmuel, Dan S Tawfik
DNA methyltransferases (MTases) constitute an attractive target for protein engineering, thus opening the road to new ways of manipulating DNA in a unique and selective manner. Here, we review various aspects of MTase engineering, both methodological and conceptual, and also discuss future directions and challenges. Bacterial MTases that are part of restriction/modification (R/M) systems offer a convenient way for the selection of large gene libraries, both in vivo and in vitro. We review these selection methods, their strengths and weaknesses, and also the prospects for new selection approaches that will enable the directed evolution of mammalian DNA methyltransferases (Dnmts)...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27826834/bacterial-dna-methylation-and-methylomes
#9
Josep Casadesús
Formation of C5-methylcytosine, N4-methylcytosine, and N6-methyladenine in bacterial genomes is postreplicative and involves transfer of a methyl group from S-adenosyl-methionine to a base embedded in a specific DNA sequence context. Most bacterial DNA methyltransferases belong to restriction-modification systems; in addition, "solitary" or "orphan" DNA methyltransferases are frequently found in the genomes of bacteria and phage. Base methylation can affect the interaction of DNA-binding proteins with their cognate sites, either by a direct effect (e...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27825927/flavin-dependent-methylation-of-rnas-complex-chemistry-for-a-simple-modification
#10
REVIEW
Djemel Hamdane, Henri Grosjean, Marc Fontecave
RNA methylation is the most abundant and evolutionarily conserved chemical modification of bases or ribose in noncoding and coding RNAs. This rather simple modification has nevertheless major consequences on the function of maturated RNA molecules and ultimately on their cellular fates. The methyl group employed in the methylation is almost universally derived from S-adenosyl-L-methionine via a simple SN2 displacement reaction. However, in some rare cases, the carbon originates from N5,N10-methylenetetrahydrofolate (CH2=THF)...
November 5, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27822545/proteome-remodeling-in-response-to-sulfur-limitation-in-candidatus-pelagibacter-ubique
#11
Daniel P Smith, Carrie D Nicora, Paul Carini, Mary S Lipton, Angela D Norbeck, Richard D Smith, Stephen J Giovannoni
The alphaproteobacterium "Candidatus Pelagibacter ubique" strain HTCC1062 and most other members of the SAR11 clade lack genes for assimilatory sulfate reduction, making them dependent on organosulfur compounds that occur naturally in seawater. To investigate how these cells adapt to sulfur limitation, batch cultures were grown in defined medium containing either limiting or nonlimiting amounts of dimethylsulfoniopropionate (DMSP) as the sole sulfur source. Protein and mRNA expression were measured before, during, and after the transition from exponential growth to stationary phase...
July 2016: MSystems
https://www.readbyqxmd.com/read/27818834/rapid-and-quantitative-determination-of-s-adenosyl-l-methionine-in-the-fermentation-process-by-surface-enhanced-raman-scattering
#12
Hairui Ren, Zhaoyang Chen, Xin Zhang, Yongmei Zhao, Zheng Wang, Zhenglong Wu, Haijun Xu
Concentrations of S-Adenosyl-L-Methionine (SAM) in aqueous solution and fermentation liquids were quantitatively determined by surface-enhanced Raman scattering (SERS) and verified by high-pressure liquid chromatography (HPLC). The Ag nanoparticle/silicon nanowire array substrate was fabricated and employed as an active SERS substrate to indirectly measure the SAM concentration. The linear relationship between the integrated intensity of peak centered at ~2920 cm(-1) in SERS spectra and the SAM concentration was established, and the limit of detections of SAM concentrations was analyzed to be ~0...
2016: Journal of Analytical Methods in Chemistry
https://www.readbyqxmd.com/read/27814539/study-on-formation-of-2-4-6-trichloroanisole-by-microbial-o-methylation-of-2-4-6-trichlorophenol-in-lake-water
#13
Kejia Zhang, Zhang Luo, Tuqiao Zhang, Minmin Mao, Jie Fu
To explore the mechanisms and influence factors on the production of 2,4,6-trichloroanisole (2,4,6-TCA) in surface waters, the 2,4,6-TCA formation potential (FP) test was conducted by incubating the real lake water with the addition of 2,4,6-trichlorophenol (2,4,6-TCP) precursor. Besides bacteria and fungi, two common cyanobacteria and algae species, i.e., Chlorella vulgaris and Anabaena flos-aquae, have been proved to have strong capabilities to produce 2,4,6-TCA, which may contribute the high 2,4,6-TCA FP (152...
October 28, 2016: Environmental Pollution
https://www.readbyqxmd.com/read/27787219/genotyping-of-cryptosporidium-spp-in-environmental-water-in-turkey
#14
Zeynep Koloren, Emine Ayaz
This research was undertaken to study the molecular detection and characterization of Cryptosporidium spp. in environmental water sources at Samsun and Giresun Provinces of The Black Sea in Turkey. Two-hundred forty and one-hundred eighty environmental samples were collected from a total of twenty and twenty-five sampling sites of Giresun and Samsun Provinces. One hundred twenty untreated drinking water samples were also detected for Cryptosporidium spp. in both investigated areas. 101 (%42), 92 (%38.3) of 240 and 74 (41...
December 1, 2016: Acta Parasitologica
https://www.readbyqxmd.com/read/27739177/directed-evolution-of-a-fluorinase-for-improved-fluorination-efficiency-with-a-non-native-substrate
#15
Huihua Sun, Wan Lin Yeo, Yee Hwee Lim, Xinying Chew, Derek John Smith, Bo Xue, Kok Ping Chan, Robert C Robinson, Edward G Robins, Huimin Zhao, Ee Lui Ang
Fluorinases offer an environmentally friendly alternative for selective fluorination under mild conditions. However, their diversity is limited in nature and they have yet to be engineered through directed evolution. Herein, we report the directed evolution of the fluorinase FlA1 for improved conversion of the non-native substrate 5'-chloro-5'-deoxyadenosine (5'-ClDA) into 5'-fluoro-5'-deoxyadenosine (5'-FDA). The evolved variants, fah2081 (A279Y) and fah2114 (F213Y, A279L), were successfully applied in the radiosynthesis of 5'-[(18) F]FDA, with overall radiochemical conversion (RCC) more than 3-fold higher than wild-type FlA1...
October 14, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27727432/s-adenosyl-methionine-same-for-depression-in-adults
#16
REVIEW
Ilaria Galizia, Lucio Oldani, Karine Macritchie, Erica Amari, Dominic Dougall, Tessa N Jones, Raymond W Lam, Guido Jacopo Massei, Lakshmi N Yatham, Allan H Young
BACKGROUND: Depression is a recurrent illness with high rates of chronicity, treatment-resistance and significant economic impact. There is evidence in the literature that S-adenosyl methionine (SAMe), a naturally occurring compound in the human body, has antidepressant efficacy. This product may be an important addition to the armamentarium of antidepressant agents. OBJECTIVES: To assess the effects of SAMe in comparison with placebo or antidepressants for the treatment of depression in adults...
October 10, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27717843/homology-modeling-of-homo-sapiens-lipoic-acid-synthase-substrate-docking-and-insights-on-its-binding-mode
#17
Ezhilarasi Krishnamoorthy, Sameer Hassan, Luke Elizabeth Hanna, Indira Padmalayam, Rama Rajaram, Vijay Viswanathan
Lipoic acid synthase (LIAS) is an iron-sulfur cluster mitochondrial enzyme which catalyzes the final step in the de novo pathway for the biosynthesis of lipoic acid, a potent antioxidant. Recently there has been significant interest in its role in metabolic diseases and its deficiency in LIAS expression has been linked to conditions such as diabetes, atherosclerosis and neonatal-onset epilepsy, suggesting a strong inverse correlation between LIAS reduction and disease status. In this study we use a bioinformatics approach to predict its structure, which would be helpful to understanding its role...
October 4, 2016: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/27703015/sequence-specific-and-shape-selective-rna-recognition-by-the-human-rna-5-methylcytosine-methyltransferase-nsun6
#18
Tao Long, Jing Li, Hao Li, Mi Zhou, Xiao-Long Zhou, Ru-Juan Liu, En-Duo Wang
Human NSun6 is an RNA methyltransferase that catalyzes the transfer of the methyl group from S-adenosyl-l-methionine (SAM) to C72 of tRNA(Thr) and tRNA(Cys) In the current study, we used mass spectrometry to demonstrate that human NSun6 indeed introduces 5-methylcytosine (m(5)C) into tRNA, as expected. To further reveal the tRNA recognition mechanism of human NSun6, we measured the methylation activity of human NSun6 and its kinetic parameters for different tRNA substrates and their mutants. We showed that human NSun6 requires a well folded, full-length tRNA as its substrate...
November 11, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27698120/stimulating-s-adenosyl-l-methionine-synthesis-extends-lifespan-via-activation-of-ampk
#19
Takafumi Ogawa, Ryohei Tsubakiyama, Muneyoshi Kanai, Tetsuya Koyama, Tsutomu Fujii, Haruyuki Iefuji, Tomoyoshi Soga, Kazunori Kume, Tokichi Miyakawa, Dai Hirata, Masaki Mizunuma
Dietary restriction (DR), such as calorie restriction (CR) or methionine (Met) restriction, extends the lifespan of diverse model organisms. Although studies have identified several metabolites that contribute to the beneficial effects of DR, the molecular mechanism underlying the key metabolites responsible for DR regimens is not fully understood. Here we show that stimulating S-adenosyl-l-methionine (AdoMet) synthesis extended the lifespan of the budding yeast Saccharomyces cerevisiae The AdoMet synthesis-mediated beneficial metabolic effects, which resulted from consuming both Met and ATP, mimicked CR...
October 18, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27689866/chemical-proteomic-profiling-of-human-methyltransferases
#20
Benjamin D Horning, Radu M Suciu, Darian A Ghadiri, Olesya A Ulanovskaya, Megan L Matthews, Kenneth M Lum, Keriann M Backus, Steven J Brown, Hugh Rosen, Benjamin F Cravatt
Methylation is a fundamental mechanism used in Nature to modify the structure and function of biomolecules, including proteins, DNA, RNA, and metabolites. Methyl groups are predominantly installed into biomolecules by a large and diverse class of S-adenosyl methionine (SAM)-dependent methyltransferases (MTs), of which there are ∼200 known or putative members in the human proteome. Deregulated MT activity contributes to numerous diseases, including cancer, and several MT inhibitors are in clinical development...
October 12, 2016: Journal of the American Chemical Society
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