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https://www.readbyqxmd.com/read/28229434/preclinical-pharmacokinetics-and-pharmacodynamics-of-pinometostat-epz-5676-a-first-in-class-small-molecule-s-adenosyl-methionine-competitive-inhibitor-of-dot1l
#1
Nigel J Waters
Acute leukemias bearing mixed lineage leukemia (MLL) rearrangements are aggressive diseases characterized by a poor overall prognosis despite multi-agent chemotherapy. Aberrant fusion proteins involving the MLL histone methyltransferase (HMT) lead to recruitment of DOT1L, to a multi-protein complex resulting in aberrant methylation of histone H3 lysine 79 at MLL target genes, and ultimately enhanced expression of critical genes for hematopoietic differentiation, including HOXA9 and MEIS1, and as such defines the established mechanism for leukemogenesis in MLL-rearrangement (MLL-r) leukemias...
February 22, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28225105/elucidating-the-biosynthetic-pathways-of-volatile-organic-compounds-in-mycobacterium-tuberculosis-through-a-computational-approach
#2
Purva Bhatter, Karthik Raman, Vani Janakiraman
Microbial volatile organic compounds (VOCs) have gained prominence in the recent past for their potential use as disease markers. The discovery of microbial VOCs has benefited 'difficult to detect' diseases such as tuberculosis (TB). Few of the identified VOCs of Mycobacterium tuberculosis (Mtb) are currently being explored for their diagnostic potential. However, very little is known about the biosynthesis of these small lipophilic molecules. Here, we propose putative biosynthetic pathways in Mycobacterium tuberculosis for three VOCs, namely methyl nicotinate, methyl phenylacetate and methyl p-anisate, using computational approaches...
February 22, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28224386/%C3%AE-bisabolol-inhibits-aspergillus-fumigatus-af239-growth-via-affecting-microsomal-%C3%A2-24-sterol-methyltransferase-as-a-crucial-enzyme-in-ergosterol-biosynthesis-pathway
#3
Zahra Jahanshiri, Masoomeh Shams-Ghahfarokhi, Farnoush Asghari-Paskiabi, Reza Saghiri, Mehdi Razzaghi-Abyaneh
Finding new compounds with antifungal properties is an important task due to the side effects of common antifungal drugs and emerging antifungal resistance in fungal strains. ∆(24)-sterol methyltransferase (24-SMT) is a crucial enzyme that plays important roles in fungal ergosterol biosynthesis pathway and is not found in humans. In the present study, the effects of α-bisabolol on Aspergillus fumigatus Af239 growth and ergosterol synthesis on the base of 24-SMT enzyme activity were studied; in addition, the expression of erg6, the gene encoded 24-SMT, was considered...
March 2017: World Journal of Microbiology & Biotechnology
https://www.readbyqxmd.com/read/28138060/rna-puzzles-round-iii-3d-rna-structure-prediction-of-five-riboswitches-and-one-ribozyme
#4
Zhichao Miao, Ryszard W Adamiak, Maciej Antczak, Robert T Batey, Alexander J Becka, Marcin Biesiada, Michał J Boniecki, Janusz Bujnicki, Shi-Jie Chen, Clarence Yu Cheng, Fang-Chieh Chou, Adrian R Ferré-D'Amaré, Rhiju Das, Wayne K Dawson, Ding Feng, Nikolay V Dokholyan, Stanisław Dunin-Horkawicz, Caleb Geniesse, Kalli Kappel, Wipapat Kladwang, Andrey Krokhotin, Grzegorz E Łach, François Major, Thomas H Mann, Marcin Magnus, Katarzyna Pachulska-Wieczorek, Dinshaw J Patel, Joseph A Piccirilli, Mariusz Popenda, Katarzyna J Purzycka, Aiming Ren, Greggory M Rice, John Santalucia, Joanna Sarzynska, Marta Szachniuk, Arpit Tandon, Jeremiah J Trausch, Siqi Tian, Jian Wang, Kevin M Weeks, Benfeard Williams, Yi Xiao, Xiaojun Xu, Dong Zhang, Tomasz Zok, Eric Westhof
RNA-Puzzles is a collective experiment in blind 3D RNA structure prediction. We report here a third round of RNA-Puzzles. Five puzzles, 4, 8, 12, 13, 14, all structures of riboswitch aptamers and puzzle 7, a ribozyme structure, are included in this round of the experiment. The riboswitch structures include biological binding sites for small molecules (S-adenosyl methionine, cyclic diadenosine monophosphate, 5-amino 4-imidazole carboxamide riboside 5'-triphosphate, glutamine) and proteins (YbxF) and one set describes large conformational changes between ligand-free and ligand-bound states; the Varkud satellite ribozyme is the most recently solved structure of a known large ribozyme...
January 30, 2017: RNA
https://www.readbyqxmd.com/read/28135835/clinical-use-of-nutraceuticals-in-the-adjunctive-treatment-of-depression-in-mood-disorders
#5
Jerome Sarris
OBJECTIVES: The aim of this paper is to detail a summary of the current evidence in this area, to better inform clinical practice. Our recent systematic reviews and meta-analyses of nutrient pharmacotherapies in the treatment unipolar depression revealed primarily positive results for replicated studies testing S-adenosyl methionine (SAMe), methylfolate, omega-3 (EPA or ethyl-EPA), and Vitamin D; with supportive isolated studies found for creatine and an amino acid combination. Mixed results were found for zinc, folic acid, Vitamin C, and tryptophan; and non-significant study results for inositol...
January 1, 2017: Australasian Psychiatry: Bulletin of Royal Australian and New Zealand College of Psychiatrists
https://www.readbyqxmd.com/read/28004936/computational-study-of-the-degradation-of-s-adenosyl-methionine-in-water
#6
Timm Lankau, Tzu Nung Kuo, Chin Hui Yu
The degradation of S-adenosyl methionine (SAM) to homoserine-γ-lactone (HSL) and methyltioadenine (MTA) in water is studied with MD simulations. The AM1 Hamiltonian is used for the quantum part and the flexible AMBER force field for the H2O molecules. The MD simulations predict the free energy barrier for the degradation reaction to be between 109 and 112 kJ mol(-1) and an overall gain in free energy of -26 kJ mol(-1). The high barrier and the low energy gain of this reaction can be linked to interactions among the carboxylate group of the SAM molecule and solvent H2O molecules, which are not observed on the product side...
January 19, 2017: Journal of Physical Chemistry. A
https://www.readbyqxmd.com/read/27997431/attenuation-of-genome-wide-5-methylcytosine-level-is-an-epigenetic-feature-of-cutaneous-malignant-melanomas
#7
Goran Micevic, Nicholas Theodosakis, Janis M Taube, Marcus W Bosenberg, Nemanja Rodić
Epigenetic modification of DNA, namely covalent changes of cytosine residues, plays a key role in the maintenance of inactive chromatin regions, both in health and in disease. In the vast majority of malignant melanomas, the most notable known epigenetic abnormality is the attenuation of 5-hydroxymethylcytosine (5-hmC) residues. However, it remains unknown whether a decrease in 5-hmC represents a primary defect of melanoma cancer epigenome or whether it is secondary to the loss of 5-methylcytosine (5-mC), a chemical substrate for 5-hmC...
December 16, 2016: Melanoma Research
https://www.readbyqxmd.com/read/27994001/stability-of-the-human-sperm-dna-methylome-to-folic-acid-fortification-and-short-term-supplementation
#8
D Chan, S McGraw, K Klein, L M Wallock, C Konermann, C Plass, P Chan, B Robaire, R A Jacob, C M T Greenwood, J M Trasler
STUDY QUESTION: Do short-term and long-term exposures to low-dose folic acid supplementation alter DNA methylation in sperm? SUMMARY ANSWER: No alterations in sperm DNA methylation patterns were found following the administration of low-dose folic acid supplements of 400 μg/day for 90 days (short-term exposure) or when pre-fortification of food with folic acid and post-fortification sperm samples (long-term exposure) were compared. WHAT IS KNOWN ALREADY: Excess dietary folate may be detrimental to health and DNA methylation profiles due to folate's role in one-carbon metabolism and the formation of S-adenosyl methionine, the universal methyl donor...
February 2017: Human Reproduction
https://www.readbyqxmd.com/read/27986076/transcriptome-analysis-in-switchgrass-discloses-ecotype-difference-in-photosynthetic-efficiency
#9
Desalegn D Serba, Srinivasa Rao Uppalapati, Nick Krom, Shreyartha Mukherjee, Yuhong Tang, Kirankumar S Mysore, Malay C Saha
BACKGROUND: Switchgrass, a warm-season perennial grass studied as a potential dedicated biofuel feedstock, is classified into two main taxa - lowland and upland ecotypes - that differ in morphology and habitat of adaptation. But there is limited information on their inherent molecular variations. RESULTS: Transcriptome analysis by RNA-sequencing (RNA-Seq) was conducted for lowland and upland ecotypes to document their gene expression variations. Mapping of transcriptome to the reference genome (Panicum virgatum v1...
December 16, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27958669/an-orthogonal-d2-o-based-induction-system-that-provides-insights-into-d-amino-acid-pattern-formation-by-radical-s-adenosylmethionine-peptide-epimerases
#10
Brandon I Morinaka, Marjan Verest, Michael F Freeman, Muriel Gugger, Jörn Piel
Radical S-adenosyl methionine peptide epimerases (RSPEs) are an enzyme family that accomplishes regiospecific and irreversible introduction of multiple d-configured residues into ribosomally encoded peptides. Collectively, RSPEs can generate diverse epimerization patterns in a wide range of substrates. Previously, the lack of rapid methods to localize epimerized residues has impeded efforts to investigate the function and applicative potential of RSPEs. An efficient mass spectrometry-based assay is introduced that permits characterization of products generated in E...
December 13, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27939670/identification-and-characterization-of-a-catechol-o-methyltransferase-cdna-in-the-catfish-heteropneustes-fossilis-tissue-sex-and-seasonal-variations-and-effects-of-gonadotropin-and-2-hydroxyestradiol-17%C3%AE-on-mrna-expression
#11
R Chaube, A Rawat, R M Inbaraj, J Bobe, Y Guiguen, A Fostier, K P Joy
Catechol-O-methyltransferase (COMT) is involved in the methylation and inactivation of endogenous and xenobiotic catechol compounds, and serves as a common biochemical link in the catecholamine and catecholestrogen metabolism. Studies on cloning, sequencing and function characterization comt gene in lower vertebrates like fish are fewer. In the present study, a full-length comt cDNA of 1442bp with an open-reading frame (ORF) of 792bp, and start codon (ATG) at nucleotide 162 and stop codon (TAG) at nucleotide 953 was isolated and characterized in the stinging catfish Heteropneustes fossilis (accession No...
December 8, 2016: General and Comparative Endocrinology
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
#12
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/27834868/steric-clash-in-the-set-domain-of-histone-methyltransferase-nsd1-as-a-cause-of-sotos-syndrome-and-its-genetic-heterogeneity-in-a-brazilian-cohort
#13
Kyungsoo Ha, Priya Anand, Jennifer A Lee, Julie R Jones, Chong Ae Kim, Debora Romeo Bertola, Jonathan D J Labonne, Lawrence C Layman, Wolfgang Wenzel, Hyung-Goo Kim
Most histone methyltransferases (HMTase) harbor a predicted Su(var)3-9, Enhancer-of-zeste, Trithorax (SET) domain, which transfers a methyl group to a lysine residue in their substrates. Mutations of the SET domains were reported to cause intellectual disability syndromes such as Sotos, Weaver, or Kabuki syndromes. Sotos syndrome is an overgrowth syndrome with intellectual disability caused by haploinsufficiency of the nuclear receptor binding SET domain protein 1 (NSD1) gene, an HMTase at 5q35.2-35.3. Here, we analyzed NSD1 in 34 Brazilian Sotos patients and identified three novel and eight known mutations...
November 9, 2016: Genes
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
#14
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/27826834/bacterial-dna-methylation-and-methylomes
#15
Josep Casadesús
Formation of C5-methylcytosine, N4-methylcytosine, and N6-methyladenine in bacterial genomes is postreplicative and involves transfer of a methyl group from S-adenosyl-methionine to a base embedded in a specific DNA sequence context. Most bacterial DNA methyltransferases belong to restriction-modification systems; in addition, "solitary" or "orphan" DNA methyltransferases are frequently found in the genomes of bacteria and phage. Base methylation can affect the interaction of DNA-binding proteins with their cognate sites, either by a direct effect (e...
2016: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/27822545/proteome-remodeling-in-response-to-sulfur-limitation-in-candidatus-pelagibacter-ubique
#16
Daniel P Smith, Carrie D Nicora, Paul Carini, Mary S Lipton, Angela D Norbeck, Richard D Smith, Stephen J Giovannoni
The alphaproteobacterium "Candidatus Pelagibacter ubique" strain HTCC1062 and most other members of the SAR11 clade lack genes for assimilatory sulfate reduction, making them dependent on organosulfur compounds that occur naturally in seawater. To investigate how these cells adapt to sulfur limitation, batch cultures were grown in defined medium containing either limiting or nonlimiting amounts of dimethylsulfoniopropionate (DMSP) as the sole sulfur source. Protein and mRNA expression were measured before, during, and after the transition from exponential growth to stationary phase...
July 2016: MSystems
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
#17
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...
December 2016: Environmental Pollution
https://www.readbyqxmd.com/read/27727432/s-adenosyl-methionine-same-for-depression-in-adults
#18
REVIEW
Ilaria Galizia, Lucio Oldani, Karine Macritchie, Erica Amari, Dominic Dougall, Tessa N Jones, Raymond W Lam, Guido Jacopo Massei, Lakshmi N Yatham, Allan H Young
BACKGROUND: Depression is a recurrent illness with high rates of chronicity, treatment-resistance and significant economic impact. There is evidence in the literature that S-adenosyl methionine (SAMe), a naturally occurring compound in the human body, has antidepressant efficacy. This product may be an important addition to the armamentarium of antidepressant agents. OBJECTIVES: To assess the effects of SAMe in comparison with placebo or antidepressants for the treatment of depression in adults...
October 10, 2016: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/27717843/homology-modeling-of-homo-sapiens-lipoic-acid-synthase-substrate-docking-and-insights-on-its-binding-mode
#19
Ezhilarasi Krishnamoorthy, Sameer Hassan, Luke Elizabeth Hanna, Indira Padmalayam, Rama Rajaram, Vijay Viswanathan
Lipoic acid synthase (LIAS) is an iron-sulfur cluster mitochondrial enzyme which catalyzes the final step in the de novo pathway for the biosynthesis of lipoic acid, a potent antioxidant. Recently there has been significant interest in its role in metabolic diseases and its deficiency in LIAS expression has been linked to conditions such as diabetes, atherosclerosis and neonatal-onset epilepsy, suggesting a strong inverse correlation between LIAS reduction and disease status. In this study we use a bioinformatics approach to predict its structure, which would be helpful to understanding its role...
October 4, 2016: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/27689866/chemical-proteomic-profiling-of-human-methyltransferases
#20
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
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