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s adenosyl l-methionine

Anthony S Gizzi, Tyler L Grove, Jamie J Arnold, Joyce Jose, Rohit K Jangra, Scott J Garforth, Quan Du, Sean M Cahill, Natalya G Dulyaninova, James D Love, Kartik Chandran, Anne R Bresnick, Craig E Cameron, Steven C Almo
Viral infections continue to represent major challenges to public health, and an enhanced mechanistic understanding of the processes that contribute to viral life cycles is necessary for the development of new therapeutic strategies 1 . Viperin, a member of the radical S-adenosyl-L-methionine (SAM) superfamily of enzymes, is an interferon-inducible protein implicated in the inhibition of replication of a broad range of RNA and DNA viruses, including dengue virus, West Nile virus, hepatitis C virus, influenza A virus, rabies virus 2 and HIV3,4 ...
June 20, 2018: Nature
Milda Mickute, Milda Nainyte, Lina Vasiliauskaite, Alexandra Plotnikova, Viktoras Masevicius, Saulius Klimašauskas, Giedrius Vilkaitis
S-adenosyl-L-methionine-dependent 2'-O-methylati-on of the 3'-terminal nucleotide plays important roles in biogenesis of eukaryotic small non-coding RNAs, such as siRNAs, miRNAs and Piwi-interacting RNAs (piRNAs). Here we demonstrate that, in contrast to Mg2+/Mn2+-dependent plant and bacterial homologues, the Drosophila DmHen1 and human HsHEN1 piRNA methyltransferases require cobalt cations for their enzymatic activity in vitro. We also show for the first time the capacity of the animal Hen1 to catalyse the transfer of a variety of extended chemical groups from synthetic analogues of the AdoMet cofactor onto a wide range (22-80 nt) of single-stranded RNAs permitting their 3'-terminal functionalization and labelling...
June 13, 2018: Nucleic Acids Research
Jing Ge, Tao Han, Xiaoqiu Li, Lili Shan, Jinhuan Zhang, Yan Hong, Yanqiu Xia, Jun Wang, Mingxiao Hou
The aim of the present study was to investigate the effects of S-adenosyl methionine (SAMe) on infectious premature inflammatory factors and uterine contraction, and to further explore its mechanism of action via the transient receptor protein 3 (TRPC3)/protein kinase Cβ (PKCβ)/C-kinase-activated protein phosphatase-1 inhibitor of 17 kDa (CPI-17) signaling pathway, following intervention by a TRPC3 inhibitor. A rat model of premature delivery induced by lipopolysaccharide (LPS) was established. Following treatment with SAMe and inhibiting TRPC3 expression, rat serum and uterus were isolated...
July 2018: Experimental and Therapeutic Medicine
Xuye Du, Huinan Wang, Jiefang He, Bin Zhu, Juan Guo, Wenqian Hou, Qingbei Weng, Xiaocun Zhang
In graminaceous plants, nicotianamine (NA) is an important component of metal acquisition. NA is synthesized from S-adenosyl-l-methionine (SAM) catalyzed by nicotianamine synthase (NAS). Here, eight Triticum monococcum NAS (TmNAS) genes were cloned and characterized. Amino acid sequence analysis showed that TmNAS genes had high sequence identity with those from Triticum aestivum, Zea mays, Oryza sativa and Hordeum vulgare. Phylogenetic analysis showed that NAS genes were classified into two distinct groups, e...
June 6, 2018: Gene
Stephanie Oerum, Martine Roovers, Robert P Rambo, Jola Kopec, Henry J Bailey, Fiona Fitzpatrick, Joseph A Newman, William G Newman, Albert Amberger, Johannes Zschocke, Louis Droogmans, Udo Oppermann, Wyatt W Yue
Mitochondrial tRNAs are transcribed as long polycistronic transcripts of precursor tRNAs and undergo posttranscriptional modifications such as endonucleolytic processing and methylation required for their correct structure and function. Among them, 5'-end processing and purine 9 N1-methylation of mitochondrial tRNA are catalysed by two proteinaceous complexes with overlapping subunit composition. The Mg2+-dependent ribonuclease P complex for 5'-end cleavage comprises the methyltransferase domain-containing protein TRMT10C/MRPP1, short-chain oxidoreductase HSD17B10/MRPP2, and metallonuclease KIAA0391/MRPP3...
June 7, 2018: Journal of Biological Chemistry
Danielle V Miller, Benjamin J Rauch, Kim Harich, Huimin Xu, John J Perona, Robert H White
The methionine salvage pathway (MSP) is critical for regeneration of S-adenosyl-l-methionine (SAM), a widely used cofactor involved in many essential metabolic reactions. The MSP has been completely elucidated in aerobic organisms, and found to rely on molecular oxygen. Since anaerobic organisms do not use O2, an alternative pathway(s) must be operating. We sought to evaluate whether the functions of two annotated MSP enzymes from Methanocaldococcus jannaschii, a methylthioinosine phosphorylase (MTIP) and a methylthioribose 1-phosphate isomerase (MTRI), are consistent with functioning in a modified anaerobic MSP (AnMSP)...
June 7, 2018: Microbiology
Sofia S Mariasina, Olga A Petrova, Ilya A Osterman, Olga V Sergeeva, Sergey V Efimov, Vladimir V Klochkov, Petr V Sergiev, Olga A Dontsova, Tai-Huang Huang, Chi-Fon Chang, Vladimir I Polshakov
Williams-Beuren syndrome is a genetic disorder characterized by physiological and mental abnormalities, and is caused by hemizygous deletion of several genes in chromosome 7. One of the removed genes encodes the WBSCR27 protein. Bioinformatic analysis of the sequence of WBSCR27 indicates that it belongs to the family of SAM-dependent methyltransferases. However, exact cellular functions of this protein or phenotypic consequences of its deficiency are still unknown. Here we report nearly complete 1 H, 15 N, and 13 C chemical shifts assignments of the 26 kDa WBSCR27 protein from Mus musculus in complex with the cofactor S-adenosyl-L-methionine (SAM)...
June 4, 2018: Biomolecular NMR Assignments
Ranjan Kumar Singh, André Feller, Martine Roovers, Dany Van Elder, Lina Wauters, Louis Droogmans, Wim Versées
tRNA molecules get heavily modified posttranscriptionally. The N-1 methylation of purines at position 9 of eukaryal and archaeal tRNA is catalyzed by the SPOUT methyltranferase Trm10. Remarkably, while certain Trm10 orthologues are specific for either guanosine or adenosine, others show a dual specificity. Structural and functional studies have been performed on guanosine- and adenosine-specific enzymes. Here we report the structure and biochemical analysis of the dual specificity enzyme from Thermococcus kodakaraensis (Tk Trm10)...
May 30, 2018: RNA
Tsehai A J Grell, Anthony P Young, Catherine L Drennan, Vahe Bandarian
TYW1 is a radical S-adenosyl-l-methionine (SAM) enzyme that catalyzes the condensation of pyruvate and N-methylguanosine to form the posttranscriptional modification, 4-demethylwyosine, in situ on transfer RNA (tRNA). Two mechanisms have been proposed for this transformation, with one of the possible mechanisms invoking a Schiff base intermediate formed between a conserved lysine residue and pyruvate. Utilizing a combination of mass spectrometry and X-ray crystallography, we have obtained evidence to support the formation of a Schiff base lysine adduct in TYW1...
May 24, 2018: Journal of the American Chemical Society
Xinyu Liu
Aliphatic carbon-halogen (C-X) bonds are prevalent in modern pharmaceuticals and bioactive natural products. Three distinct chemical strategies are known in Nature to generate these structural motifs. The first is via the nucleophilic substitution at a prefunctionalized electrophilic carbon center with a halide anion (X- ), known for the S-adenosyl-l-methionine-dependent halogenases. The second is via the electrophilic activation of an alkene or its equivalent by a halenium ion (X+ ) donor, known for the haloperoxidases and flavin-dependent halogenases...
2018: Methods in Enzymology
Tony D Davis, Sylvia Kunakom, Michael D Burkart, Alessandra S Eustaquio
S-adenosyl-l-methionine (SAM) is universal in biology, serving as the second most common cofactor in a variety of enzymatic reactions. One of the main roles of SAM is the methylation of nucleic acids, proteins, and metabolites. Methylation often imparts regulatory control to DNA and proteins, and leads to an increase in the activity of specialized metabolites such as those developed as pharmaceuticals. There has been increased interest in using SAM analogs in methyltransferase-catalyzed modification of biomolecules...
2018: Methods in Enzymology
Nadezhda A Timofeyeva, Alexandra Yu Ryazanova, Maxim V Norkin, Tatiana S Oretskaya, Olga S Fedorova, Elena A Kubareva
Type II restriction⁻modification (RM) systems are the most widespread bacterial antiviral defence mechanisms. DNA methyltransferase SsoII (M.SsoII) from a Type II RM system SsoII regulates transcription in its own RM system in addition to the methylation function. DNA with a so-called regulatory site inhibits the M.SsoII methylation activity. Using circular permutation assay, we show that M.SsoII monomer induces DNA bending of 31° at the methylation site and 46° at the regulatory site. In the M.SsoII dimer bound to the regulatory site, both protein subunits make equal contributions to the DNA bending, and both angles are in the same plane...
May 16, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
Pieter C Steketee, Isabel M Vincent, Fiona Achcar, Federica Giordani, Dong-Hyun Kim, Darren J Creek, Yvonne Freund, Robert Jacobs, Kevin Rattigan, David Horn, Mark C Field, Annette MacLeod, Michael P Barrett
The parasitic protozoan Trypanosoma brucei causes Human African Trypanosomiasis and Nagana in other mammals. These diseases present a major socio-economic burden to large areas of sub-Saharan Africa. Current therapies involve complex and toxic regimens, which can lead to fatal side-effects. In addition, there is emerging evidence for drug resistance. AN5568 (SCYX-7158) is a novel benzoxaborole class compound that has been selected as a lead compound for the treatment of HAT, and has demonstrated effective clearance of both early and late stage trypanosomiasis in vivo...
May 14, 2018: PLoS Neglected Tropical Diseases
Daria Krefft, Aliaksei Papkov, Maciej Prusinowski, Agnieszka Zylicz-Stachula, Piotr M Skowron
BACKGROUND: Acoustic or hydrodynamic shearing, sonication and enzymatic digestion are used to fragment DNA. However, these methods have several disadvantages, such as DNA damage, difficulties in fragmentation control, irreproducibility and under-representation of some DNA segments. The DNA fragmentation tool would be a gentle enzymatic method, offering cleavage frequency high enough to eliminate DNA fragments distribution bias and allow for easy control of partial digests. Only three such frequently cleaving natural restriction endonucleases (REases) were discovered: CviJI, SetI and FaiI...
May 11, 2018: BMC Genomics
Darja Deobald, Lorenz Adrian, Christian Schöne, Michael Rother, Gunhild Layer
The biological formation of methane (methanogenesis) is a globally important process, which is exploited in biogas technology, but also contributes to global warming through the release of a potent greenhouse gas into the atmosphere. The last and methane-releasing step of methanogenesis is catalysed by the enzyme methyl-coenzyme M reductase (MCR), which carries several exceptional posttranslational amino acid modifications. Among these, a 5-C-(S)-methylarginine is located close to the active site of the enzyme...
May 9, 2018: Scientific Reports
Hsin-Yu Lee, Radu M Suciu, Benjamin D Horning, Ekaterina V Vinogradova, Olesya A Ulanovskaya, Benjamin F Cravatt
Nicotinamide N-methyltransferase (NNMT) catalyzes the N-methylation of nicotinamide using S-adenosyl-L-methionine (SAM) as a methyl donor and, through doing so, can modulate cellular methylation potential to impact diverse epigenetic processes. NNMT has been implicated in a range of diseases, including cancer and metabolic disorders. Potent, selective, and cell-active inhibitors would constitute valuable probes to study the biological functions and therapeutic potential of NNMT. We previously reported the discovery of electrophilic small molecules that inhibit NNMT by reacting with an active-site cysteine residue in the SAM-binding pocket...
April 10, 2018: Bioorganic & Medicinal Chemistry Letters
Zhen Liu, Miao Fan, Chao Li, Jian-Hong Xu
The plant O-methyltransferases are dependent on S-Adenosyl-l-methionine, which can catalyze a variety of secondary metabolites. Here we identified different number of OMT genes from the respective grass genomes. Phylogenetic analysis showed that this OMT gene family is a grass-specific gene family that is different from COMT. Most of genes were expanded by tandem and segment duplication after the species split from their progenitor. Furthermore, genes from Group I and two clusters from group II are only present in Panicoideae, which included Bx10 and Bx7 involved in the benzoxazinoids pathway, suggesting these genes could participate in insect resistance in Panicoideae...
April 22, 2018: Genomics
Ludovic Halby, Nils Marechal, Dany Pechalrieu, Vincent Cura, Don-Marc Franchini, Céline Faux, Fréderic Alby, Nathalie Troffer-Charlier, Srikanth Kudithipudi, Albert Jeltsch, Wahiba Aouadi, Etienne Decroly, Jean-Claude Guillemot, Patrick Page, Clotilde Ferroud, Luc Bonnefond, Dominique Guianvarc'h, Jean Cavarelli, Paola B Arimondo
DNA, RNA and histone methylation is implicated in various human diseases such as cancer or viral infections, playing a major role in cell process regulation, especially in modulation of gene expression. Here we developed a convergent synthetic pathway starting from a protected bromomethylcytosine derivative to synthesize transition state analogues of the DNA methyltransferases. This approach led to seven 5-methylcytosine-adenosine compounds that were, surprisingly, inactive against hDNMT1, hDNMT3Acat, TRDMT1 and other RNA human and viral methyltransferases...
June 5, 2018: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
Silvia I Mora, Jonathan García-Román, Iván Gómez-Ñañez, Rebeca García-Román
Chronic liver diseases result in overall deterioration of health status and changes in metabolism. The search for strategies to control and combat these hepatic diseases has witnessed a great boom in the last decades. Nutritional therapy for controlling and managing liver diseases may be a positive influence as it improves the function of the liver. In this review, we focus mainly on describing liver conditions such as nonalcoholic fatty liver disease, and intrahepatic cholestasis as well as using S-adenosyl-L-methionine as a dietary supplement and its potential alternative therapeutic effect to correct the hepatic dysfunction associated with these conditions...
April 20, 2018: European Journal of Gastroenterology & Hepatology
Kazuki Tanifuji, Chi Chung Lee, Nathaniel S Sickerman, Kazuyuki Tatsumi, Yasuhiro Ohki, Yilin Hu, Markus W Ribbe
The M-cluster is the [(homocitrate)MoFe7 S9 C] active site of nitrogenase that is derived from an 8Fe core assembled viacoupling and rearrangement of two [Fe4 S4 ] clusters concomitant with the insertion of an interstitial carbon and a 'ninth sulfur'. Combining synthetic [Fe4 S4 ] clusters with an assembly protein template, here we show that sulfite can give rise to the ninth sulfur that is incorporated in the catalytically important belt region of the cofactor after the radical S-adenosyl-L-methionine-dependent carbide insertion and the concurrent 8Fe-core rearrangement have already taken place...
May 2018: Nature Chemistry
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