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s adenosyl l-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/27834682/does-viperin-function-as-a-radical-s-adenosyl-l-methionine-dependent-enzyme-in-regulating-farnesylpyrophosphate-synthase-expression-and-activity
#4
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
#5
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
#6
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
#7
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/27825927/flavin-dependent-methylation-of-rnas-complex-chemistry-for-a-simple-modification
#8
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/27818834/rapid-and-quantitative-determination-of-s-adenosyl-l-methionine-in-the-fermentation-process-by-surface-enhanced-raman-scattering
#9
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
#10
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
#11
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
#12
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/27703015/sequence-specific-and-shape-selective-rna-recognition-by-the-human-rna-5-methylcytosine-methyltransferase-nsun6
#13
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
#14
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
#15
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
https://www.readbyqxmd.com/read/27685665/design-of-potent-and-druglike-nonphenolic-inhibitors-for-catechol-o-methyltransferase-derived-from-a-fragment-screening-approach-targeting-the-s-adenosyl-l-methionine-pocket
#16
Christian Lerner, Roland Jakob-Roetne, Bernd Buettelmann, Andreas Ehler, Markus Rudolph, Rosa María Rodríguez Sarmiento
A fragment screening approach designed to target specifically the S-adenosyl-l-methionine pocket of catechol O-methyl transferase allowed the identification of structurally related fragments of high ligand efficiency and with activity on the described orthogonal assays. By use of a reliable enzymatic assay together with X-ray crystallography as guidance, a series of fragment modifications revealed an SAR and, after several expansions, potent lead compounds could be obtained. For the first time nonphenolic and small low nanomolar potent, SAM competitive COMT inhibitors are reported...
October 14, 2016: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27648579/a-histone-h3k9m-mutation-traps-histone-methyltransferase-clr4-to-prevent-heterochromatin-spreading
#17
Chun-Min Shan, Jiyong Wang, Ke Xu, Huijie Chen, Jia-Xing Yue, Stuart Andrews, James J Moresco, John R Yates, Peter L Nagy, Liang Tong, Songtao Jia
Histone lysine-to-methionine (K-to-M) mutations are associated with multiple cancers, and they function in a dominant fashion to block the methylation of corresponding lysines on wild type histones. However, their mechanisms of function are controversial. Here we show that in fission yeast, introducing the K9M mutation into one of the three histone H3 genes dominantly blocks H3K9 methylation on wild type H3 across the genome. In addition, H3K9M enhances the interaction of histone H3 tail with the H3K9 methyltransferase Clr4 in a SAM (S-adenosyl-methionine)-dependent manner, and Clr4 is trapped at nucleation sites to prevent its spreading and the formation of large heterochromatin domains...
September 20, 2016: ELife
https://www.readbyqxmd.com/read/27648357/ezh2-inhibitors-transcriptionally-upregulate-cytotoxic-autophagy-and-cytoprotective-unfolded-protein-response-in-human-colorectal-cancer-cells
#18
Yao-Yu Hsieh, Hsiang-Ling Lo, Pei-Ming Yang
Enhancer of zeste homolog 2 (EZH2) has been emerged as novel anticancer target. Various EZH2 small-molecule inhibitors have been developed in recent years. A major class of EZH2 inhibitors are S-adenosyl-L-methionine (SAM)-competitive inhibitors, such as EPZ005687, EI1, GSK126, UNC1999 and GSK343. Autophagy, a physiological process of self-digestion, is involved in the turnover of proteins or intracellular organelles. It can serve as cytoprotective or cytotoxic function in cancer. Our previous study has found that UNC1999 and GSK343 are potent autophagy inducers...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27642865/carbon-extension-in-peptidylnucleoside-biosynthesis-by-radical-sam-enzymes
#19
Edward A Lilla, Kenichi Yokoyama
Nikkomycins and polyoxins are antifungal peptidylnucleoside antibiotics active against human and plant pathogens. Here we report that during peptidylnucleoside biosynthesis in Streptomyces cacaoi and S. tendae, the C5' extension of the nucleoside essential for downstream structural diversification is catalyzed by a conserved radical S-adenosyl-L-methionine (SAM) enzyme, PolH or NikJ. This is distinct from the nucleophilic mechanism reported for antibacterial nucleosides and represents a new mechanism of nucleoside natural product biosynthesis...
November 2016: Nature Chemical Biology
https://www.readbyqxmd.com/read/27629654/crystal-structures-of-the-bifunctional-trna-methyltransferase-trm5a
#20
Caiyan Wang, Qian Jia, Ran Chen, Yuming Wei, Juntao Li, Jie Ma, Wei Xie
tRNA methyltransferase Trm5 catalyses the transfer of a methyl group from S-adenosyl-L-methionine to G37 in eukaryotes and archaea. The N1-methylated guanosine is the product of the initial step of the wyosine hypermodification, which is essential for the maintenance of the reading frame during translation. As a unique member of this enzyme family, Trm5a from Pyrococcus abyssi (PaTrm5a) catalyses not only the methylation of N1, but also the further methylation of C7 on 4-demethylwyosine at position 37 to produce isowyosine, but the mechanism for the double methylation is poorly understood...
2016: Scientific Reports
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