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s adenyl methionine

Tahir Hussain, Manickam Yogavel, Amit Sharma
Aminoacyl-tRNA synthetases (aaRSs) are housekeeping enzymes that couple cognate tRNAs with amino acids to transmit genomic information for protein translation. The Plasmodium falciparum nuclear genome encodes two P. falciparum methionyl-tRNA synthetases (PfMRS), termed PfMRS(cyt) and PfMRS(api). Phylogenetic analyses revealed that the two proteins are of primitive origin and are related to heterokonts (PfMRS(cyt)) or proteobacteria/primitive bacteria (PfMRS(api)). We show that PfMRS(cyt) localizes in parasite cytoplasm, while PfMRS(api) localizes to apicoplasts in asexual stages of malaria parasites...
April 2015: Antimicrobial Agents and Chemotherapy
Carolin Lübker, Ramona J Bieber Urbauer, Jackob Moskovitz, Stefan Dove, Jasmin Weisemann, Maria Fedorova, Jeffrey L Urbauer, Roland Seifert
Membranous adenylyl cyclase 1 (AC1) is associated with memory and learning. AC1 is activated by the eukaryotic Ca(2+)-sensor calmodulin (CaM), which contains nine methionine residues (Met) important for CaM-target interactions. During ageing, Met residues are oxidized to (S)- and (R)-methionine sulfoxide (MetSO) by reactive oxygen species arising from an age-related oxidative stress. We examined how oxidation by H2O2 of Met in CaM regulates CaM activation of AC1. We employed a series of thirteen mutant CaM proteins never assessed before in a single study, where leucine is substituted for Met, in order to analyze the effects of oxidation of specific Met...
January 15, 2015: Biochemical Pharmacology
Ahmad H Al-Mestarihi, Germán Villamizar, Javier Fernández, Olga E Zolova, Felipe Lombó, Sylvie Garneau-Tsodikova
The antitumor agent thiocoraline is a nonribosomally biosynthesized bisintercalator natural product, which contains in its peptidic backbone two S-methylated l-cysteine residues. S-Methylation occurs very rarely in nature, and is observed extremely rarely in nonribosomal peptide scaffolds. We have proposed that during thiocoraline biosynthesis, TioN, a stand-alone adenylation domain interrupted by the S-adenosyl-l-methionine binding region of a methyltransferase enzyme, is capable of performing two functions: the adenylation and S-methylation of l-cysteine...
December 10, 2014: Journal of the American Chemical Society
Harit Ravi Kant, M Balamurali, Sankaranarayanan Meenakshisundaram
S-Adenosyl-L-methionine (SAM) is an important metabolite having prominent role in treating various diseases. Due to increasing demand of SAM, improvement in its production is essential. For this purpose, S-adenosyl-l-methionine synthetase gene (sam2) was overexpressed in the present study, and we studied the effect of coexpression of methionine permease (mup1) and adenylate kinase (adk1) genes. From the recombinant strains expressing individual genes, we observed that SAM2 synthetase is the primary limiting factor and its overexpression is essential to increase the SAM productivity...
October 20, 2014: Journal of Biotechnology
Alexey Kulikovsky, Marina Serebryakova, Olga Bantysh, Anastasia Metlitskaya, Sergei Borukhov, Konstantin Severinov, Svetlana Dubiley
Translation inhibitor microcin C (McC) is a heptapeptide with an aspartate α-carboxyl group linked to AMP via phosphoramidate bond. Modification of the McC phosphate by an aminopropyl moiety increases the biological activity by ~10-fold. Here, we determine the pathway of the aminopropylation reaction of McC. We show that the MccD enzyme uses S-adenosyl methionine to transfer 3-amino-3-carboxypropyl group onto a phosphate of an McC maturation intermediate consisting of adenylated heptapeptide. The carboxyl group is removed by the MccE enzyme, yielding mature McC...
August 6, 2014: Journal of the American Chemical Society
A B Giles, D Grierson, H Smith
Poly(A)-containing messenger RNA was purified from polyribosomes isolated from the primary leaves of 7-day-old dark-grown seedlings of Phaseolus vulgaris var. Masterpiece. Analysis of the messenger RNA on 2.4% polyacrylamide gels showed that it consists of a heterogeneous population of molecules with an average molecular weight of 500,000. The nucleotide composition of the RNA was 16.0% cytidylic acid, 39.4% adenylic acid, 21.3% guanylic acid and 23.2% uridylic acid. Based on the degree of resistance of the RNA to digestion with ribonucleases A and T1 the average length of the poly(A) sequence was calculated to be 120 nucleotides...
January 1977: Planta
Jia-Xue Cao, Hong-Ping Zhang, Li-Xin Du
DNA methylation is catalyzed by a family of DNA methyltransferases (DNMTs) that transfer a methyl group from S-adenyl methionine (SAM) to the fifth carbon of a cytosine residue to form 5mC. DNA methylation affects the interaction between the histone and DNA, which changes the chromosome structure and has reverse relationship with gene expression in general. Up to now, more and more studies have confirmed that environmental factors can alter epigenetic modifications, which do not involve in changing DNA sequence...
July 2013: Yi Chuan, Hereditas
Filipe Cabreiro, Catherine Au, Kit-Yi Leung, Nuria Vergara-Irigaray, Helena M Cochemé, Tahereh Noori, David Weinkove, Eugene Schuster, Nicholas D E Greene, David Gems
The biguanide drug metformin is widely prescribed to treat type 2 diabetes and metabolic syndrome, but its mode of action remains uncertain. Metformin also increases lifespan in Caenorhabditis elegans cocultured with Escherichia coli. This bacterium exerts complex nutritional and pathogenic effects on its nematode predator/host that impact health and aging. We report that metformin increases lifespan by altering microbial folate and methionine metabolism. Alterations in metformin-induced longevity by mutation of worm methionine synthase (metr-1) and S-adenosylmethionine synthase (sams-1) imply metformin-induced methionine restriction in the host, consistent with action of this drug as a dietary restriction mimetic...
March 28, 2013: Cell
Cho Yeow Koh, Jessica E Kim, Sayaka Shibata, Ranae M Ranade, Mingyan Yu, Jiyun Liu, J Robert Gillespie, Frederick S Buckner, Christophe L M J Verlinde, Erkang Fan, Wim G J Hol
To guide development of new drugs targeting methionyl-tRNA synthetase (MetRS) for treatment of human African trypanosomiasis, crystal structure determinations of Trypanosoma brucei MetRS in complex with its substrate methionine and its intermediate product methionyl-adenylate were followed by those of the enzyme in complex with high-affinity aminoquinolone inhibitors via soaking experiments. Drastic changes in conformation of one of the two enzymes in the asymmetric unit allowed these inhibitors to occupy an enlarged methionine pocket and a new so-called auxiliary pocket...
October 10, 2012: Structure
Pengjuan Gong, Junhong Zhang, Hanxia Li, Changxian Yang, Chanjuan Zhang, Xiaohui Zhang, Ziaf Khurram, Yuyang Zhang, Taotao Wang, Zhangjun Fei, Zhibiao Ye
To unravel the molecular mechanisms of drought responses in tomato, gene expression profiles of two drought-tolerant lines identified from a population of Solanum pennellii introgression lines, and the recurrent parent S. lycopersicum cv. M82, a drought-sensitive cultivar, were investigated under drought stress using tomato microarrays. Around 400 genes identified were responsive to drought stress only in the drought-tolerant lines. These changes in genes expression are most likely caused by the two inserted chromosome segments of S...
August 2010: Journal of Experimental Botany
E Galindo, M F Bader, D Aunis
Abstract In the present study we investigated the regulation of Chromogranin A (CGA) and Chromogranin B (CGB) biosynthesis in bovine chromaffin cells maintained in primary culture. Cellular proteins were labelled with [(35)S]methionine and the incorporated radioactivity was used as an index of the synthesis rate. The radioactivity incorporated into CGA was determined by immunoprecipitation, and that into CGB was quantified by a dot immunobinding assay using specific antibodies. Incubation of cells with carbamylcholine, nigh K(+) or histamine, three potent stimulators of catecholamine secretion in chromaffin cells, increased the rate of CGA and CGB synthesis...
December 1, 1991: Journal of Neuroendocrinology
Pilar Caro, Jose Gomez, Inés Sanchez, Ruben Garcia, Monica López-Torres, Alba Naudí, Manuel Portero-Otin, Reinald Pamplona, Gustavo Barja
Previous studies have shown that the decrease in mitochondrial reactive oxygen species (mitROS) generation and oxidative damage to mitochondrial DNA (mtDNA) that occurs during life extending dietary restriction also occurs during protein or methionine restriction, whereas it does not take place during carbohydrate or lipid restriction. In order to study the possible effects of other amino acids, in this investigation all the dietary amino acids, except methionine, were restricted by 40% in male Wistar rats (RESTAAS group)...
October 2009: Biogerontology
Stanislav Kopriva, Kai Fritzemeier, Gertrud Wiedemann, Ralf Reski
Sulfate assimilation provides reduced sulfur for synthesis of the amino acids cysteine and methionine and for a range of other metabolites. Sulfate has to be activated prior to reduction by adenylation to adenosine 5'-phosphosulfate (APS). In plants, algae, and many bacteria, this compound is reduced to sulfite by APS reductase (APR); in fungi and some cyanobacteria and gamma-proteobacteria, a second activation step, phosphorylation to 3'-phosphoadenosine 5'-phosphosulfate (PAPS), is necessary before reduction to sulfite by PAPS reductase (PAPR)...
August 3, 2007: Journal of Biological Chemistry
Diane M Hargrove, Eric S Kendall, James M Reynolds, Aung N Lwin, John P Herich, Pamela A Smith, Bronislava R Gedulin, Shawn D Flanagan, Carolyn M Jodka, Julie A Hoyt, Kevin M McCowen, David G Parkes, Christen M Anderson
Exenatide, the active ingredient of BYETTA (exenatide injection), is an incretin mimetic that has been developed for the treatment of patients with type 2 diabetes. Exenatide binds to and activates the known GLP-1 receptor with a potency comparable to that of the mammalian incretin GLP-1(7-36), thereby acting as a glucoregulatory agent. AC3174 is an analog of exenatide with leucine substituted for methionine at position 14, [Leu(14)]exendin-4. The purpose of these studies was to evaluate the glucoregulatory activity and pharmacokinetics of AC3174...
June 7, 2007: Regulatory Peptides
M D Vaughan, P B Sampson, E Daub, J F Honek
Aminoacyl-tRNA synthetases catalyze the stepwise coupling of specific amino acid substrates to their cognate tRNAs. The first intermediate formed in this process is the aminoacyl-adenylate, which then subsequently reacts with the 3'-terminus of the cognate tRNA to transfer the amino acid to the tRNA. This overall reaction is critical for protein biosynthesis and is quintessential to the viability of all organisms. Therefore, the selective inhibition of bacterial amino acid-tRNA synthetases is the focus of intense current interest for the development of novel antibacterial agents...
May 2005: Medicinal Chemistry
Adrian S Ray, Brenda I Hernandez-Santiago, Judy S Mathew, Eisuke Murakami, Carey Bozeman, Meng-Yu Xie, Ginger E Dutschman, Elizabeth Gullen, Zhenjun Yang, Selwyn Hurwitz, Yung-Chi Cheng, Chung K Chu, Harold McClure, Raymond F Schinazi, Karen S Anderson
To better understand the importance of the oxygen in the ribose ring of planar unsaturated nucleoside analogs that target human immunodeficiency virus (HIV), a 6-cyclopropyl-substituted prodrug of 2',3'-didehydro-2',3'-dideoxyguanosine (cyclo-d4G) was synthesized, and its cellular metabolism, antiviral activity, and pharmacokinetic behavior were studied. Cyclo-d4G had selective anti-HIV activity in primary blood mononuclear cells (PBMCs), effectively inhibiting the LAI strain of HIV-1 by 50% at 1.1 +/- 0.1 microM while showing 50% inhibition of cell viability at 84...
May 2005: Antimicrobial Agents and Chemotherapy
Ioannis S Elefsiniotis, Ioannis Ketikoglou, Georgia Kafiri, Konstantinos D Pantazis, Antonios Moulakakis, Christos Mavrogiannis
OBJECTIVE: Lamivudine is a nucleoside analogue with potent antiviral activity against hepatitis B virus (HBV). Plasma pituitary adenylate cyclase activating polypeptide (PACAP) is a multifunctional neuropeptide that is produced within the lymphoid microenvironment and induces the production of Th2-type cytokines. The aim of our study was to investigate the possible alterations of plasma PACAP-38 levels in chronic hepatitis B (CHB) patients during lamivudine treatment and to compare them with biochemical, virological and histological data...
November 2003: European Journal of Gastroenterology & Hepatology
Limei Yan, Angus C Nairn, H Clive Palfrey, Matthew J Brady
The role of elongation factor (EF)-2 phosphorylation in the regulation of pancreatic beta-cell protein synthesis by glucose was investigated in the INS-1-derived cell line 832/13. Incubation of cells in media containing 1 mm glucose resulted in a progressive increase in EF-2 phosphorylation that was maximal by 1-2 h. Readdition of 10 mm glucose promoted a rapid dephosphorylation of EF-2 that was complete in 10 min and maintained over the ensuing 2 h. Similar results were obtained using primary rat islets or Min-6 insulinoma cells...
May 16, 2003: Journal of Biological Chemistry
Katherine Herbig, En-Pei Chiang, Ling-Ru Lee, Jessica Hills, Barry Shane, Patrick J Stover
Folate-dependent one-carbon metabolism is required for the synthesis of purines and thymidylate and for the remethylation of homocysteine to methionine. Methionine is subsequently adenylated to S-adenosylmethionine (SAM), a cofactor that methylates DNA, RNA, proteins, and many metabolites. Previous experimental and theoretical modeling studies have indicated that folate cofactors are limiting for cytoplasmic folate-dependent reactions and that the synthesis of DNA precursors competes with SAM synthesis. Each of these studies concluded that SAM synthesis has a higher metabolic priority than dTMP synthesis...
October 11, 2002: Journal of Biological Chemistry
R T Smolenski
Rapid resynthesis of the adenylate pool in cardiac myocytes is important for recovery of contractility and normal function of regulatory mechanisms in the heart. Adenosine and adenine are thought to be the most effective substrates for nucleotide synthesis, but the possibility of using other compounds has been studied very little in cardiomyocytes. In the present study, the effect of S-adenosyl-L-methionine (SAM) on the adenylate pool of isolated cardiomyocytes was investigated and compared to the effect of adenine and adenosine...
2000: Acta Biochimica Polonica
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