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S-Adenosyl methionine

Dimitrios Tsikas, Erik Hanff, Alexander Bollenbach
S-Adenosyl-L-methionine (SAM) is a cofactor serving as a methyl donor in numerous enzymatic reactions. It has been reported that SAM has the potential to modify antioxidant-enzymes, glutathione-biosynthesis and methionine adenosyltransferases-1/2 in hepatitis C virus -expressing cells at millimolar concentrations. The efficacy of SAM at micromolar concentrations and the underlying mechanisms remain to be demonstrated.
October 28, 2017: World Journal of Gastroenterology: WJG
Justin A North, Anthony R Miller, John A Wildenthal, Sarah J Young, F Robert Tabita
Numerous cellular processes involving S-adenosyl-l-methionine result in the formation of the toxic by-product, 5'-methylthioadenosine (MTA). To prevent inhibitory MTA accumulation and retain biologically available sulfur, most organisms possess the "universal" methionine salvage pathway (MSP). However, the universal MSP is inherently aerobic due to a requirement of molecular oxygen for one of the key enzymes. Here, we report the presence of an exclusively anaerobic MSP that couples MTA metabolism to ethylene formation in the phototrophic bacteria Rhodospirillum rubrum and Rhodopseudomonas palustris In vivo metabolite analysis of gene deletion strains demonstrated that this anaerobic MSP functions via sequential action of MTA phosphorylase (MtnP), 5-(methylthio)ribose-1-phosphate isomerase (MtnA), and an annotated class II aldolase-like protein (Ald2) to form 2-(methylthio)acetaldehyde as an intermediate...
November 13, 2017: Proceedings of the National Academy of Sciences of the United States of America
Brent M Robicheau, Adèle L Bunbury-Blanchette, Kurt LaButti, Igor V Grigoriev, Allison K Walker
We describe the complete mating-type (MAT) locus for Phialocephala scopiformis Canadian Collection of Fungal Cultures (DAOMC) 229536 - a basal lineage within Vibrisseaceae. This strain is of interest due to its ability to produce the important antiinsectan rugulosin. We also provide some of the first insights into the genome structure and gene inventory of nonclavicipitalean endophytes. Sequence was obtained through shotgun sequencing of the entire P. scopiformis genome, and the MAT locus was then determined by comparing this genomic sequence to known MAT loci within the Phialocephala fortinii s...
December 2017: Fungal Biology
Xiao Shu, Qing Dai, Tong Wu, Ian R Bothwell, Yanan Yue, Zezhou Zhang, Jie Cao, Qili Fei, Minkui Luo, Chuan He, Jianzhao Liu
RNA labeling is crucial for the study of RNA structure and metabolism. Herein we report N(6)-allyladenosine (a(6)A) as a new small molecule for RNA labeling through both metabolic and enzyme-assisted manners. a(6)A behaves like A and can be metabolically incorporated into newly synthesized RNAs inside mammalian cells. We also show that human RNA N(6)-methyladenosine (m(6)A) methyltransferases METTL3/METTL14 can work with a synthetic cofactor, namely allyl-SAM (S-adenosyl methionine with methyl replaced by allyl) in order to site-specifically install an allyl group to the N(6)-position of A within specific sequence to generate a(6)A-labeled RNAs...
November 15, 2017: Journal of the American Chemical Society
Gwenn G Parungao, Mojun Zhao, Qinzhe Wang, Stephen P Zano, Ronald E Viola, Robert M Blumenthal
S-adenosyl-l-methionine (AdoMet) is an essential metabolite, playing a wide variety of metabolic roles. The enzyme that produces AdoMet from l-methionine and ATP (methionine adenosyltransferase, MAT) is thus an attractive target for anti-cancer and antimicrobial agents. It would be very useful to have a system that allows rapid identification of species-specific inhibitors of this essential enzyme. A previously generated E. coli strain, lacking MAT (∆metK) but containing a heterologous AdoMet transporter, was successfully complemented with heterologous metK genes from several bacterial pathogens, as well as with MAT genes from a fungal pathogen and Homo sapiens...
November 7, 2017: Microbiology
Shuntaro Machida, Ranjith K Bakku, Iwane Suzuki
In living organisms, modified fatty acids are crucial for the functions of the cellular membranes and storage lipids where the fatty acids are esterified. Some bacteria produce a typical methyl-branched fatty acid, i.e., 10-methyl stearic acid (19:0Me10). The biosynthetic pathway of 19:0Me10 in vivo has not been demonstrated clearly yet. It had been speculated that 19:0Me10 is synthesized from oleic acid (18:1Δ9) by S-adenosyl-L-methionine-dependent methyltransfer and NADPH-dependent reduction via a methylenated intermediate, 10-methyelene octadecanoic acid...
2017: Frontiers in Microbiology
Lakshmi Prabhu, Lan Chen, Han Wei, Özlem Demir, Ahmad Safa, Lifan Zeng, Rommie E Amaro, Bert H O'Neil, Zhon-Yin Zhang, Tao Lu
The protein arginine methyltransferase (PRMT) family of enzymes comprises nine family members in mammals. They catalyze arginine methylation, either monomethylation or symmetric/asymmetric dimethylation of histone and non-histone proteins. PRMT methylation of its substrate proteins modulates cellular processes such as signal transduction, transcription, and mRNA splicing. Recent studies have linked overexpression of PRMT5, a member of the PRMT superfamily, to oncogenesis, making it a potential target for cancer therapy...
November 3, 2017: Molecular BioSystems
Rahul Gopalam, Sunny D Rupwate, Ajay W Tumaney
Quantitative real-time polymerase chain reaction (qRT-PCR) has become the most popular choice for gene expression studies. For accurate expression analysis, it is pertinent to select a stable reference gene to normalize the data. It is now known that the expression of internal reference genes varies considerably during developmental stages and under different experimental conditions. For Salvia hispanica, an economically important oilseed crop, there are no reports of stable reference genes till date. In this study, we chose 13 candidate reference genes viz...
2017: PloS One
Hak Joong Kim, Yung-Nan Liu, Reid M McCarty, Hung-Wen Liu
Many cobalamin (Cbl)-dependent radical S-adenosyl-l-methionine (SAM) methyltransferases have been identified through sequence alignment and/or genetic analysis; however, few have been studied in vitro. GenK is one such enzyme that catalyzes methylation of the 6'-carbon of gentamicin X2 (GenX2) to produce G418 during the biosynthesis of gentamicins. Reported herein, several alternative substrates and fluorinated substrate analogs were prepared to investigate the mechanism of methyl transfer from Cbl to the substrate as well as the substrate specificity of GenK...
November 15, 2017: Journal of the American Chemical Society
Yan Zhang, Xin-Yan Wang, Qianyi Zhang, Chun-Yang Zhang
DNA methyltransferases (MTases) may specifically recognize the short palindromic sequences and transfer a methyl group from S-adenosyl-l-methionine to target cytosine/adenine. The aberrant DNA methylation is linked to the abnormal DNA MTase activity, and some DNA MTases have become promising targets of anticancer/antimicrobial drugs. However, the reported DNA MTase assays often involve laborious operation, expensive instruments, and radio-labeled substrates. Here, we develop a simple and label-free fluorescent method to sensitively detect DNA adenine methyltransferase (Dam) on the basis of terminal deoxynucleotidyl transferase (TdT)-activated Endonuclease IV (Endo IV)-assisted hyperbranched amplification...
November 7, 2017: Analytical Chemistry
Antonio F Tiburcio, Rubén Alcázar
The synthesis of spermidine, spermine and thermospermine requires the addition of aminopropyl groups from decarboxylated S-adenosyl-methionine (dSAM). The synthesis of dSAM is catalyzed by S-adenosylmethionine decarboxylase. dSAM levels are usually low, which constitutes a rate-limiting factor in the synthesis of polyamines. In this chapter, we provide a protocol for the determination of SAMDC activity in plants through the detection of radiolabelled CO2 released during the SAMDC reaction.
2018: Methods in Molecular Biology
Kenichi Yokoyama
The radical SAM (S-adenosyl-l-methionine) superfamily is one of the largest group of enzymes with >113000 annotated sequences [Landgraf, B. J., et al. (2016) Annu. Rev. Biochem. 85, 485-514]. Members of this superfamily catalyze the reductive cleavage of SAM using an oxygen sensitive 4Fe-4S cluster to transiently generate 5'-deoxyadenosyl radical that is subsequently used to initiate diverse free radical-mediated reactions. Because of the unique reactivity of free radicals, radical SAM enzymes frequently catalyze chemically challenging reactions critical for the biosynthesis of unique structures of cofactors and natural products...
November 9, 2017: Biochemistry
Chie Tomikawa, Kazuyuki Takai, Hiroyuki Hori
TrmB is a eubacterial tRNA methyltransferase which catalyzes the formation of N 7-methylguanosine at position 46 (m 7 G46) in tRNA consuming S-adenosyl-L-methionine (AdoMet) as the methyl group donor during the reaction. Previously, we purified TrmB from Aquifex aeolicus , a hyper-thermophilic eubacterium, and clarified the recognition sites in tRNA. Furthermore, we reported that an additional C-terminal region of A. aeolicus TrmB is required for protein stability at high temperatures. In the current study, we devised a new purification method to remove contaminating RNA completely...
October 23, 2017: Journal of Biochemistry
Jianshe Zhang, Cheng Liu, Shujiang Zhao, Shaoyu Guo, Bin Shen
In this study, we sequenced and characterized an interferon-stimulated gene Viperin homologue, LcViperin, from large yellow croaker (Larimichthys crocea). The LcViperin encodes 354 amino acids and contains an N-terminal amphipathic α-helix domain, a radical S-adenosyl-l-methionine (SAM) domain and a highly conserved C-terminal domain. The analyses of LcViperin promoter region revealed nine kinds of putative transcriptional factor binding sites, including five putative ICSBP (IRF-8) binding sites and one putative IRF-1 binding site, indicating that the expression of LcViperin might be induced by the type I IFN response...
October 21, 2017: Developmental and Comparative Immunology
Jaimee R Compton, Matthew J Mickey, Xin Hu, Juan J Marugan, Patricia M Legler
The alphaviral nsP2 cysteine protease of the Venezuelan equine encephalitis virus (VEEV) is a validated antiviral drug target. Clan CN proteases contain a cysteine protease domain that is intimately packed with an S-adenosyl-l-methionine-dependent RNA methyltransferase (SAM MTase) domain. Within a cleft formed at the interface of these two domains, the peptide substrate is thought to bind. The nucleophilic cysteine can be found within a conserved motif, (475)NVCWAK(480), which differs from that of papain ((22)CGSCWAFS(29))...
November 9, 2017: Biochemistry
Kilmer S McCully
Many pathogenic microorganisms have been demonstrated in atherosclerotic plaques and in cerebral plaques in dementia. Hyperhomocysteinemia, which is a risk factor for atherosclerosis and dementia, is caused by dysregulation of methionine metabolism secondary to deficiency of the allosteric regulator, adenosyl methionine. Deficiency of adenosyl methionine results from increased polyamine biosynthesis by infected host cells, causing increased activity of ornithine decarboxylase, decreased nitric oxide and peroxynitrate formation and impaired immune reactions...
2017: Frontiers in Aging Neuroscience
Qudeer Ahmed Abdul, Byung Pal Yu, Hae Young Chung, Hyun Ah Jung, Jae Sue Choi
Epigenetics oftenly described as the heritable changes in gene expression independent of changes in DNA sequence. Various environmental factors such as nutrition-dietary components, lifestyle, exercise, physical activity, toxins, and other contributing factors remodel the genome either in a constructive or detrimental way. Since epigenetic changes are reversible and nutrition is one of the many epigenetic regulators that modify gene expression without changing the DNA sequence, dietary nutrients and bioactive food components contribute to epigenetic phenomena either by directly suppressing DNA methylation or histone catalyzing enzymes or by changing the availability of substrates required for enzymatic reactions...
October 17, 2017: Archives of Pharmacal Research
Kanhaiya Singh, Durba Pal, Mithun Sinha, Subhadip Ghatak, Surya C Gnyawali, Savita Khanna, Sashwati Roy, Chandan K Sen
Hyperglycemia (HG) induces genome-wide cytosine demethylation. Our previous work recognized miR-200b as a critical angiomiR, which must be transiently downregulated to initiate wound angiogenesis. Under HG, miR-200b downregulation is not responsive to injury. Here, we demonstrate that HG may drive vasculopathy by epigenetic modification of a miR promoter. In human microvascular endothelial cells (HMECs), HG also lowered DNA methyltransferases (DNMT-1 and DNMT-3A) and compromised endothelial function as manifested by diminished endothelial nitric oxide (eNOS), lowered LDL uptake, impaired Matrigel tube formation, lower NO production, and compromised VE-cadherin expression...
September 12, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
Eleonora Gatta, James Auta, David P Gavin, Dulal K Bhaumik, Dennis R Grayson, Subhash C Pandey, Alessandro Guidotti
BACKGROUND: Cerebellum is an area of the brain particularly sensitive to the effects of acute and chronic alcohol consumption. Alcohol exposure decreases cerebellar Purkinje cell output by increasing GABA release from Golgi cells onto extrasynaptic α6/δ-containing GABAA receptors located on glutamatergic granule cells. Here, we studied whether chronic alcohol consumption induces changes in GABAA receptor subunit expression and whether these changes are associated with alterations in epigenetic mechanisms via DNA methylation...
August 19, 2017: International Journal of Neuropsychopharmacology
Shanshan Zhao, Wei Hong, Jianguo Wu, Yu Wang, Shaoyi Ji, Shuyi Zhu, Chunhong Wei, Jinsong Zhang, Yi Li
Ethylene plays critical roles in plant development and biotic stress response, but the mechanism of ethylene in host antiviral response remains unclear. Here, we report that Rice dwarf virus (RDV) triggers ethylene production by stimulating the activity of S-adenosyl-L-methionine synthetase (SAMS), a key component of the ethylene synthesis pathway, resulting in elevated susceptibility to RDV. RDV-encoded Pns11 protein specifically interacted with OsSAMS1 to enhance its enzymatic activity, leading to higher ethylene levels in both RDV-infected and Pns11-overexpressing rice...
October 10, 2017: ELife
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