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s adenosyl l-methionine

Natsaran Saichana, Katsuyuki Tanizawa, Hiroshi Ueno, Jiří Pechoušek, Petr Novák, Jitka Frébortová
PqqE is a radical S-adenosyl-l-methionine (SAM) enzyme that catalyzes the initial reaction of pyrroloquinoline quinone (PQQ) biosynthesis. PqqE belongs to the SPASM (subtilosin/PQQ/anaerobic sulfatase/mycofactocin maturating enzymes) subfamily of the radical SAM superfamily and contains multiple Fe-S clusters. To characterize the Fe-S clusters in PqqE from Methylobacterium extorquens AM1, Cys residues conserved in the N-terminal signature motif (CX 3 CX 2C) and the C-terminal seven-cysteine motif (CX 9-15 GX 4 CX n CX 2 CX 5 CX 3 CX n C; n = an unspecified number) were individually or simultaneously mutated into Ser...
December 2017: FEBS Open Bio
Bin Wang, Shiqiang Wang, Zhezhi Wang
The plant SABATH gene family is a group of O-methyltransferases (O-MTs), which belongs to the S-adenosyl-l-methionine-dependent methyltransferases (SAM-MTs). The resulting reaction products of SABATH genes play an important role in various processes of plant development. In this study, a total of 30 SABATH genes were detected in Salvia miltiorrhiza, which is an important medicinal plant, widely used to treat cardiovascular disease. Multiple sequence alignment and phylogenetic analyses showed that SmSABATH genes could be classified into three groups...
December 5, 2017: Genes
Geng Dong, Lili Cao, Ulf Ryde
Lipoyl synthase (LipA) catalyses the final step of the biosynthesis of the lipoyl cofactor by insertion of two sulfur atoms at the C6 and C8 atoms of the protein-bound octanoyl substrate. In this reaction, two [4Fe4S] clusters and two molecules of S-adenosyl-L-methionine are used. One of the two FeS clusters is responsible for the generation of a powerful oxidant, the 5'-deoxyadenosyl radical (5'-dA•). The other (the auxiliary cluster) is the source of both sulfur atoms that are inserted into the substrate...
December 4, 2017: Journal of Biological Inorganic Chemistry: JBIC
K J Pampa, S Madan Kumar, M K Hema, Karthik Kumara, S Naveen, Naoki Kunishima, N K Lokanath
Methyltransferases (MTs) are enzymes involved in methylation that are needed to perform cellular processes such as biosynthesis, metabolism, gene expression, protein trafficking and signal transduction. The cofactor S-adenosyl-L-methionine (SAM) is used for catalysis by SAM-dependent methyltransferases (SAM-MTs). The crystal structure of Pyrococcus horikoshii SAM-MT was determined to a resolution of 2.1 Å using X-ray diffraction. The monomeric structure consists of a Rossmann-like fold (domain I) and a substrate-binding domain (domain II)...
December 1, 2017: Acta Crystallographica. Section F, Structural Biology Communications
Lea Anhäuser, Fabian Muttach, Andrea Rentmeister
Methyltransferases are powerful tools for site-specific transfer of non-natural functional groups from synthetic analogs of their cosubstrate S-adenosyl-l-methionine (AdoMet). We present a new class of AdoMet analogs containing photo-caging (PC) groups in their side chain, enzymatic transfer of PC groups by a promiscuous DNA MTase as well as light-triggered removal from the target DNA. This strategy provides a new avenue to reversibly modulate the functionality of DNA at MTase target sites.
November 29, 2017: Chemical Communications: Chem Comm
Wei Xu, Sumit Mukherjee, Yu Ning, Fong-Fu Hsu, Kai Zhang
Cyclopropane fatty acid synthase (CFAS) catalyzes the transfer of a methylene group from S-adenosyl methionine to an unsaturated fatty acid, generating a cyclopropane fatty acid (CFA). The gene encoding CFAS is present in many bacteria and several Leishmania spp. including Leishmania mexicana, Leishmania infantum and Leishmania braziliensis. In this study, we characterized the CFAS-null and -overexpression mutants in L. mexicana, the causative agent for cutaneous leishmaniasis in Mexico and central America...
November 24, 2017: International Journal for Parasitology
Lili Pan, Jianteng Sun, X Chris Le, Lizhong Zhu
Contamination of organic pollutants in the environment is usually accompanied by heavy metals. However, a little information on the influences of heavy metals on the uptake, translocation and transformation of organic pollutants in plants is available. In this study, ten-day hydroponic exposure was conducted to explore the influence of copper (Cu) on the bioaccumulation and biotransformation of polychlorinated biphenyls (PCBs) in intact young rice (Oryza sativa L.). Low dose of Cu (≤100 μmol/L) increased the accumulation of CB-61 in rice plants, while excess concentrations of Cu (>100 μmol/L) inhibited uptake and translocation of CB-61...
November 13, 2017: Chemosphere
Lisanne M Fermin, Sarah J Pain, Patrick C H Morel, Kristene R Gedye, Paul R Kenyon, Hugh T Blair
Progesterone (P4), acting via its receptor, regulates uterine function and histotroph production, which are crucial to embryo growth. This study aimed to examine exogenous P4 effects on embryo size and differential endometrial gene expression at Day 19 of gestation using a 'dam size' sheep model of maternal constraint. Purebred Suffolk (S, genotypically large) embryos were transferred into recipient groups of Cheviot (C, genotypically small) or Suffolk ewes that had, or had not, been pre-treated with P4 from Days 0 to 6 of pregnancy...
November 21, 2017: Reproduction, Fertility, and Development
Harshini Neelakantan, Virginia Vance, Michael D Wetzel, Hua-Yu Leo Wang, Stanton F McHardy, Celeste C Finnerty, Jonathan D Hommel, Stanley J Watowich
There is a critical need for new mechanism-of-action drugs that reduce the burden of obesity and associated chronic metabolic comorbidities. A potentially novel target to treat obesity and type 2 diabetes is nicotinamide-N-methyltransferase (NNMT), a cytosolic enzyme with newly identified roles in cellular metabolism and energy homeostasis. To validate NNMT as an anti-obesity drug target, we investigated the permeability, selectivity, mechanistic, and physiological properties of a series of small molecule NNMT inhibitors...
November 15, 2017: Biochemical Pharmacology
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
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 21, 2017: Molecular BioSystems
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
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
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