s adenosylmethionine

Summary

Summary: Physiologic methyl radical donor involved in enzymatic transmethylation reactions and present in all living organisms. It possesses anti-inflammatory activity and has been used in treatment of chronic liver disease. (From Merck, 11th ed)

Top Publications

  1. ncbi SAM (dependent) I AM: the S-adenosylmethionine-dependent methyltransferase fold
    Jennifer L Martin
    Centre for Drug Design and Development, and Special Research Centre for Functional and Applied Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane QLD 4072, Australia
    Curr Opin Struct Biol 12:783-93. 2002
  2. ncbi S-adenosylmethionine: jack of all trades and master of everything?
    W A M Loenen
    Department of Toxicogenetics, Division 5, Leiden University Medical Centre, Building 2, T 03 011, Einthovenweg, Leiden, The Netherlands
    Biochem Soc Trans 34:330-3. 2006
  3. ncbi The Radical SAM Superfamily
    Perry A Frey
    Department of Biochemistry, University of Madison, Wisconin Madison, Wisconsin 53726, USA
    Crit Rev Biochem Mol Biol 43:63-88. 2008
  4. pmc AdoMet-dependent methylation, DNA methyltransferases and base flipping
    X Cheng
    Emory University School of Medicine, Department of Biochemistry, 1510 Clifton Road, Atlanta, GA 30322, USA
    Nucleic Acids Res 29:3784-95. 2001
  5. ncbi Crystal structure of the S-adenosylmethionine synthetase ternary complex: a novel catalytic mechanism of S-adenosylmethionine synthesis from ATP and Met
    Junichi Komoto
    Department of Molecular Biosciences, University of Kansas, 1200 Sunnyside Avenue, Lawrence, Kansas 66045 7534, USA
    Biochemistry 43:1821-31. 2004
  6. ncbi Mechanism of stimulation of catalytic activity of Dnmt3A and Dnmt3B DNA-(cytosine-C5)-methyltransferases by Dnmt3L
    Humaira Gowher
    International University Bremen, School of Engineering and Science, Campus Ring 1, 28759 Bremen, Germany
    J Biol Chem 280:13341-8. 2005
  7. ncbi Discovery of two novel radical S-adenosylmethionine proteins required for the assembly of an active [Fe] hydrogenase
    Matthew C Posewitz
    National Renewable Energy Laboratory, Colorado School of Mines, Golden, CO 80401, USA
    J Biol Chem 279:25711-20. 2004
  8. pmc Comparative genomics of the methionine metabolism in Gram-positive bacteria: a variety of regulatory systems
    Dmitry A Rodionov
    Institute for Information Transmission Problems, Russian Academy of Sciences, Bolshoi Karetny pereulok 19, Moscow 127994, Russia
    Nucleic Acids Res 32:3340-53. 2004
  9. ncbi RNA methylation under heat shock control
    H Bugl
    Department of Biology, University of Michigan, Ann Arbor 48109, USA
    Mol Cell 6:349-60. 2000
  10. pmc Crystal structure of the S-adenosylmethionine-dependent enzyme MoaA and its implications for molybdenum cofactor deficiency in humans
    Petra Hänzelmann
    Department of Biochemistry, Center for Structural Biology, State University of New York, Stony Brook, NY 11794 5115, USA
    Proc Natl Acad Sci U S A 101:12870-5. 2004

Detail Information

Publications276 found, 100 shown here

  1. ncbi SAM (dependent) I AM: the S-adenosylmethionine-dependent methyltransferase fold
    Jennifer L Martin
    Centre for Drug Design and Development, and Special Research Centre for Functional and Applied Genomics, Institute for Molecular Bioscience, University of Queensland, Brisbane QLD 4072, Australia
    Curr Opin Struct Biol 12:783-93. 2002
    ..Over the past two years, there has been a significant increase in the number of structures that are known to incorporate this fold, including several uncharacterized proteins and two proteins that lack methyltransferase activity...
  2. ncbi S-adenosylmethionine: jack of all trades and master of everything?
    W A M Loenen
    Department of Toxicogenetics, Division 5, Leiden University Medical Centre, Building 2, T 03 011, Einthovenweg, Leiden, The Netherlands
    Biochem Soc Trans 34:330-3. 2006
    ..This minireview discusses some of these diverse and amazing roles of this small metabolite...
  3. ncbi The Radical SAM Superfamily
    Perry A Frey
    Department of Biochemistry, University of Madison, Wisconin Madison, Wisconsin 53726, USA
    Crit Rev Biochem Mol Biol 43:63-88. 2008
    ....
  4. pmc AdoMet-dependent methylation, DNA methyltransferases and base flipping
    X Cheng
    Emory University School of Medicine, Department of Biochemistry, 1510 Clifton Road, Atlanta, GA 30322, USA
    Nucleic Acids Res 29:3784-95. 2001
    ..Several newly discovered MTase families in eukaryotes (DNA 5mC MTases and protein arginine and lysine MTases) offer new challenges in the MTase field...
  5. ncbi Crystal structure of the S-adenosylmethionine synthetase ternary complex: a novel catalytic mechanism of S-adenosylmethionine synthesis from ATP and Met
    Junichi Komoto
    Department of Molecular Biosciences, University of Kansas, 1200 Sunnyside Avenue, Lawrence, Kansas 66045 7534, USA
    Biochemistry 43:1821-31. 2004
    ..Pajares, M. A., Hermoso, J. A., Guillerm, D., Guillerm, G., and Sanz-Aparicio. J. (2003) J. Mol. Biol. 331, 407] is substantially different from our mechanism...
  6. ncbi Mechanism of stimulation of catalytic activity of Dnmt3A and Dnmt3B DNA-(cytosine-C5)-methyltransferases by Dnmt3L
    Humaira Gowher
    International University Bremen, School of Engineering and Science, Campus Ring 1, 28759 Bremen, Germany
    J Biol Chem 280:13341-8. 2005
    ..Following dissociation of Dnmt3L, Dnmt3A adopts a closed conformation leading to slow rates of DNA release. Therefore, Dnmt3L acts as a substrate exchange factor that accelerates DNA and AdoMet binding to de novo DNA methyltransferases...
  7. ncbi Discovery of two novel radical S-adenosylmethionine proteins required for the assembly of an active [Fe] hydrogenase
    Matthew C Posewitz
    National Renewable Energy Laboratory, Colorado School of Mines, Golden, CO 80401, USA
    J Biol Chem 279:25711-20. 2004
    ..This represents the first report on the nature of the accessory genes required for the maturation of an active [Fe] hydrogenase...
  8. pmc Comparative genomics of the methionine metabolism in Gram-positive bacteria: a variety of regulatory systems
    Dmitry A Rodionov
    Institute for Information Transmission Problems, Russian Academy of Sciences, Bolshoi Karetny pereulok 19, Moscow 127994, Russia
    Nucleic Acids Res 32:3340-53. 2004
    ..In particular, Oceanobacillus iheyensis possibly uses a homolog of the betaine-homocysteine methyltransferase bhmT gene from vertebrates to substitute missing bacterial-type methionine synthases...
  9. ncbi RNA methylation under heat shock control
    H Bugl
    Department of Biology, University of Michigan, Ann Arbor 48109, USA
    Mol Cell 6:349-60. 2000
    ..Null mutations in ftsJ show a dramatically altered ribosome profile, a severe growth disadvantage, and a temperature-sensitive phenotype. Our results reveal an unexpected link between the heat shock response and RNA metabolism...
  10. pmc Crystal structure of the S-adenosylmethionine-dependent enzyme MoaA and its implications for molybdenum cofactor deficiency in humans
    Petra Hänzelmann
    Department of Biochemistry, Center for Structural Biology, State University of New York, Stony Brook, NY 11794 5115, USA
    Proc Natl Acad Sci U S A 101:12870-5. 2004
    ..The noncysteinyl-ligated unique Fe site of the C-terminal [4Fe-4S] cluster is proposed to be involved in the binding and activation of 5'-GTP...
  11. pmc Many paths to methyltransfer: a chronicle of convergence
    Heidi L Schubert
    Department of Biochemistry, University of Utah, Salt Lake City 84132 3201, USA
    Trends Biochem Sci 28:329-35. 2003
    ..Even within a particular MTase class the amino-acid sequence similarity can be as low as 10%. Thus, the structural and catalytic requirements for methyltransfer from AdoMet appear to be remarkably flexible...
  12. ncbi Domain alternation switches B(12)-dependent methionine synthase to the activation conformation
    Vahe Bandarian
    Biophysics Research Division and Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan 48109 1055, USA
    Nat Struct Biol 9:53-6. 2002
    ....
  13. ncbi S-Adenosyl-L-methionine (SAMe): from the bench to the bedside--molecular basis of a pleiotrophic molecule
    Teodoro Bottiglieri
    Baylor University Medical Center, Institute of Metabolic Disease, Dallas, TX 75226, USA
    Am J Clin Nutr 76:1151S-7S. 2002
    ..This article provides an overview of the biochemical, molecular, and therapeutic effects of this pleiotrophic molecule...
  14. ncbi Protein arginine methylation: Cellular functions and methods of analysis
    Steffen Pahlich
    Biochemisches Institut, Universitat Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland
    Biochim Biophys Acta 1764:1890-903. 2006
    ....
  15. ncbi In the cystathionine beta-synthase knockout mouse, elevations in total plasma homocysteine increase tissue S-adenosylhomocysteine, but responses of S-adenosylmethionine and DNA methylation are tissue specific
    Silvina F Choumenkovitch
    Vitamin Metabolism Laboratory, Jean Mayer U S Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA
    J Nutr 132:2157-60. 2002
    ....
  16. ncbi S-adenosylmethionine and its products
    M A Grillo
    Dipartimento di Medicina e Oncologia Sperimentale, Sezione di Biochimica, Universita di Torino, Torino, Italy
    Amino Acids 34:187-93. 2008
    ....
  17. pmc S-adenosylmethionine stabilizes cystathionine beta-synthase and modulates redox capacity
    Anna Prudova
    Redox Biology Center and Biochemistry Department, University of Nebraska, Lincoln, NE 68588 0664, USA
    Proc Natl Acad Sci U S A 103:6489-94. 2006
    ..A mechanistic basis for the coordinate changes in redox and methylation metabolism that are a hallmark of several complex diseases is explained by these observations...
  18. ncbi DNA cytosine C5 methyltransferase Dnmt1: catalysis-dependent release of allosteric inhibition
    Zeljko M Svedruzić
    Department of Chemistry and Biochemistry, University of California, Santa Barbara, California 93106, USA
    Biochemistry 44:9472-85. 2005
    ..We describe limitations in the Michaelis-Menten kinetic analysis of Dnmt1 and suggest alternative approaches...
  19. pmc Radical SAM, a novel protein superfamily linking unresolved steps in familiar biosynthetic pathways with radical mechanisms: functional characterization using new analysis and information visualization methods
    H J Sofia
    Applied Mathematics, Environmental Molecular Sciences Laboratory EMSL, Pacific Northwest National Laboratory, Richland, WA 99352, USA
    Nucleic Acids Res 29:1097-106. 2001
    ..Two functional predictions for unknown proteins are made based on integrating other data types such as motif, domain, operon and biochemical pathway into an organized view of similarity relationships...
  20. pmc AdoMet radical proteins--from structure to evolution--alignment of divergent protein sequences reveals strong secondary structure element conservation
    Yvain Nicolet
    Department of Chemistry 16 573, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA
    Nucleic Acids Res 32:4015-25. 2004
    ..These differences in barrel architecture also explain how AdoMet radical enzymes can act on substrates that range in size from 10 atoms to 608 residue proteins...
  21. ncbi Plasma S-adenosylhomocysteine is a more sensitive indicator of cardiovascular disease than plasma homocysteine
    D M Kerins
    Departments of Biochemistry and Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA
    Am J Clin Nutr 74:723-9. 2001
    ..Both plasma total homocysteine and S-adenosylhomocysteine are significantly correlated with plasma creatinine in patients...
  22. ncbi Reconstitution and mechanism of the stimulation of de novo methylation by human DNMT3L
    Michael S Kareta
    Section of Molecular and Cellular Biology and Center for Genetics and Development, University of California, Davis, California 95616, USA
    J Biol Chem 281:25893-902. 2006
    ..Binding of DNMT3L to DNMT3A2 promotes a dramatic reorganization of DNMT3A2 subunits and leads to the formation of specific complexes with enhanced DNA methyltransferase activity and increased SAM binding...
  23. ncbi The crystal structure of MT0146/CbiT suggests that the putative precorrin-8w decarboxylase is a methyltransferase
    Jacob P Keller
    Department of Biological Sciences, 702A Fairchild Center, MC2434, Columbia University, New York, NY 10027, USA
    Structure 10:1475-87. 2002
    ..Therefore, MT0146/CbiT probably functions as a precorrin methyltransferase and represents the first enzyme identified with this activity that does not have the canonical precorrin methyltransferase fold...
  24. ncbi Riboswitches that sense S-adenosylmethionine and S-adenosylhomocysteine
    Joy Xin Wang
    Department of Molecular, Cellular and Developmental Biology, Yale University, 266 Whitney Avenue, New Haven, CT 06520, USA
    Biochem Cell Biol 86:157-68. 2008
    ....
  25. pmc Human mitochondrial transcription factor B1 interacts with the C-terminal activation region of h-mtTFA and stimulates transcription independently of its RNA methyltransferase activity
    Vicki McCulloch
    Department of Biochemistry, Rollins Research Center, Emory University School of Medicine, Atlanta, Georgia 30322 3050, USA
    Mol Cell Biol 23:5816-24. 2003
    ..Altogether, these data provide important new insight into the mechanism of transcription initiation in human mitochondria and indicate that the dual functions of h-mtTFB1 can be separated...
  26. ncbi Aclacinomycin 10-hydroxylase is a novel substrate-assisted hydroxylase requiring S-adenosyl-L-methionine as cofactor
    Anna Jansson
    Department of Medical Biochemistry and Biophysics, Karolinska Institutet, S 171 77 Stockholm, Sweden
    J Biol Chem 280:3636-44. 2005
    ..The enzyme lacks methyltransferase activity due to the positioning of the AdoMet methyl group unfavorable for a SN2-type methyl transfer to the substrate...
  27. pmc Mutational analysis of conserved residues in HhaI DNA methyltransferase
    Umesh T Sankpal
    Department of Biochemistry, Indian Institute of Science, Bangalore 560012, India
    Nucleic Acids Res 30:2628-38. 2002
    ..This study implies plasticity in the recognition of cofactor by HhaI DNA methyltransferase...
  28. pmc A mechanism for S-adenosyl methionine assisted formation of a riboswitch conformation: a small molecule with a strong arm
    Wei Huang
    Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803, USA
    Nucleic Acids Res 37:6528-39. 2009
    ..An electrostatic potential map reveals a 'hot spot' at the Mg binding site in the presence of SAM. These results suggest that SAM binding helps to position J1/2 in a manner that is favorable for P1 helix formation...
  29. ncbi Reductive cleavage of S-adenosylmethionine by biotin synthase from Escherichia coli
    Sandrine Ollagnier-de Choudens
    Laboratoire de Chimie et Biochimie des Centres Redox Biologiques, Departement de Biologie Moléculaire et Structurale Chimie Biologie, CEA CNRS Université Joseph Fourier, UMR 5047, Grenoble, France
    J Biol Chem 277:13449-54. 2002
    ....
  30. pmc Aquifex aeolicus tRNA (N2,N2-guanine)-dimethyltransferase (Trm1) catalyzes transfer of methyl groups not only to guanine 26 but also to guanine 27 in tRNA
    Takako Awai
    Department of Materials Science and Biotechnology, Graduate School of Science and Engineering, Ehime University, Bunkyo 3, Matsuyama, Ehime 790 8577
    J Biol Chem 284:20467-78. 2009
    ..Moreover, we prepared an additional 22 mutant tRNA transcripts and clarified that the recognition sites exist in the T-arm structure. This long distance recognition results in multisite recognition by the enzyme...
  31. ncbi Hypermethylation of the cap structure of both yeast snRNAs and snoRNAs requires a conserved methyltransferase that is localized to the nucleolus
    John Mouaikel
    Institut de Genetique Moleculaire, IFR 24 CNRS UMR 5535, 1919 Route de Mende, 34000 Montpellier, France
    Mol Cell 9:891-901. 2002
    ..Consistently, Tgs1p is also localized in the nucleolus. Our results suggest a trafficking pathway in which yeast snRNAs and snoRNAs cycle through the nucleolus to undergo m(7)G cap hypermethylation...
  32. ncbi Structure of the SAM-II riboswitch bound to S-adenosylmethionine
    Sunny D Gilbert
    Department of Chemistry and Biochemistry, Campus Box 215, University of Colorado, Boulder, Colorado 80309, USA
    Nat Struct Mol Biol 15:177-82. 2008
    ..Chemical probing of this RNA in the absence and presence of ligand shows how the structure changes in response to S-adenosylmethionine to sequester the ribosomal binding site and affect translational gene regulation...
  33. ncbi S-adenosylmethionine/homocysteine cycle alterations modify DNA methylation status with consequent deregulation of PS1 and BACE and beta-amyloid production
    Andrea Fuso
    Laboratorio di Ricerca, Dipartimento di Chirurgia P Valdoni, Universita di Roma La Sapienza, 00161 Rome, Italy
    Mol Cell Neurosci 28:195-204. 2005
    ..The use of deprived medium was intended to mimic a mild nutritional deficit involved in the onset of AD...
  34. pmc Generation of cell-to-cell signals in quorum sensing: acyl homoserine lactone synthase activity of a purified Vibrio fischeri LuxI protein
    A L Schaefer
    Department of Microbiology, University of Iowa, Iowa City 52242, USA
    Proc Natl Acad Sci U S A 93:9505-9. 1996
    ....
  35. pmc The crystal structure of Nep1 reveals an extended SPOUT-class methyltransferase fold and a pre-organized SAM-binding site
    Alexander B Taylor
    Department of Biochemistry, X ray Crystallography Core Laboratory, The University of Texas Health Science Center San Antonio, San Antonio, TX 78229, USA
    Nucleic Acids Res 36:1542-54. 2008
    ..Therefore, our structures together with previous genetic data suggest that Nep1 is a genuine rRNA methyltransferase...
  36. ncbi S-adenosylmethionine conformations in solution and in protein complexes: conformational influences of the sulfonium group
    George D Markham
    The Institute for Cancer Research, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, Pennsylvania 19111, USA
    Biochemistry 41:7636-46. 2002
    ..The sulfonium sulfur is in van der Waals contact with a protein heteroatom in the structures of four proteins, which reflects an energetically favorable contact. Interactions of the sulfonium with aromatic rings are rarely observed...
  37. ncbi Electron-nuclear double resonance spectroscopic evidence that S-adenosylmethionine binds in contact with the catalytically active [4Fe-4S](+) cluster of pyruvate formate-lyase activating enzyme
    Charles J Walsby
    Department of Chemistry, Northwestern University, Evanston, Illinois 60208 3113, USA
    J Am Chem Soc 124:3143-51. 2002
    ..We have used this information to construct a model for the interaction of AdoMet with the [4Fe-4S](2+/+) cluster of PFL-AE and have proposed a mechanism for radical generation that is consistent with these results...
  38. pmc Probing a rate-limiting step by mutational perturbation of AdoMet binding in the HhaI methyltransferase
    Egle Merkiene
    Laboratory of Biological DNA Modification, Institute of Biotechnology LT 02241 Vilnius, Lithuania
    Nucleic Acids Res 33:307-15. 2005
    ..Our analysis indicates that the rate-limiting breakdown of a long-lived ternary product complex is initiated by the dissociation of AdoHcy or the opening of the catalytic loop in the enzyme...
  39. ncbi A dimeric viral SET domain methyltransferase specific to Lys27 of histone H3
    Karishma L Manzur
    Structural Biology Program, Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, One Gustave L Levy Place, New York, New York 10029, USA
    Nat Struct Biol 10:187-96. 2003
    ..Cofactor S-adenosyl-L-methionine (SAM) binds at the opening of the beta-barrel, and amino acids C-terminal to Lys27 in H3 and in the flexible C-terminal tail of the enzyme confer the specificity of this viral histone methyltransferase...
  40. ncbi Direct transfer of extended groups from synthetic cofactors by DNA methyltransferases
    Christian Dalhoff
    Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, D 52056 Aachen, Germany
    Nat Chem Biol 2:31-2. 2006
    ....
  41. ncbi Insight into the polar reactivity of the onium chalcogen analogues of S-adenosyl-L-methionine
    David F Iwig
    Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA
    Biochemistry 43:13496-509. 2004
    ..In the accompanying paper, we use the information obtained in these model studies to probe the mechanism of cyclopropane fatty acid synthase via use of the onium chalcogens of AdoMet as methyl donors...
  42. ncbi Biochemical characterization of the HydE and HydG iron-only hydrogenase maturation enzymes from Thermatoga maritima
    Jon K Rubach
    Laboratoire de Chimie et Biochimie des Centres Redox Biologiques, UMR 5047, Département Réponses et Dynamiques Cellulaires, CEA Grenoble, 17 rue des Martyrs, 38054 Grenoble Cedex 9, France
    FEBS Lett 579:5055-60. 2005
    ..The HydG protein binds one [4Fe-4S] cluster, and probably an additional one. Both enzymes are able to reductively cleave S-adenosylmethionine (SAM) when reduced by dithionite, confirming that they are Radical-SAM enzymes...
  43. ncbi Simultaneous detection of S-adenosylmethionine and S-adenosylhomocysteine in mouse and rat tissues by capillary electrophoresis
    Eric O Uthus
    USDA ARS Grand Forks Human Nutrition Research Center, Grand Forks, ND 58202, USA
    Electrophoresis 24:1221-6. 2003
    ..The method is linear over ranges of 1-100 microM SAM and 1-250 microM SAH. This method can be used to determine tissue concentrations of SAM and SAH, two metabolites that can provide insight into many biological processes...
  44. ncbi Lipoyl synthase requires two equivalents of S-adenosyl-L-methionine to synthesize one equivalent of lipoic acid
    Robert M Cicchillo
    Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania 16802, USA
    Biochemistry 43:6378-86. 2004
    ..Last, our data indicate that 2 equiv of AdoMet are cleaved irreversibly in forming 1 equiv of [lipoyl]H-protein and are consistent with a model in which two LipA proteins are required to synthesize one lipoyl group...
  45. ncbi gamma-Secretase is differentially modulated by alterations of homocysteine cycle in neuroblastoma and glioblastoma cells
    Andrea Fuso
    Department of Surgery P Valdoni, University of Rome La Sapienza, Rome, Italy
    J Alzheimers Dis 11:275-90. 2007
    ..Moreover, we found that homocysteine alterations had an effect on neuroblastoma but not on glioblastoma cells; this suggests a possible differential role of the two cell types in Alzheimer disease...
  46. ncbi A mathematical model of the methionine cycle
    Michael C Reed
    Department of Mathematics, Duke University, Durham, NC 27708, USA
    J Theor Biol 226:33-43. 2004
    ..We conduct computational "experiments" that give understanding of the regulatory behavior of the methionine cycle under normal conditions and the behavior in the presence of genetic variation and dietary deficiencies...
  47. pmc A pathogenic linked mutation in the catalytic core of human cystathionine beta-synthase disrupts allosteric regulation and allows kinetic characterization of a full-length dimer
    Suvajit Sen
    Redox Biology Center and the Biochemistry Department, University of Nebraska, Lincoln, Nebraska 68588 0664, USA
    Biochemistry 46:4110-6. 2007
    ..Furthermore, analysis of individual single mutations has permitted, for the first time, partial kinetic characterization of a full-length dimeric form of human cystathionine beta-synthase...
  48. ncbi The structure of the C-terminal domain of methionine synthase: presenting S-adenosylmethionine for reductive methylation of B12
    M M Dixon
    Biophysics Research Division, University of Michigan, 930 N University, Ann Arbor, MI 48109 1055, USA
    Structure 4:1263-75. 1996
    ..The structures of the AdoMet binding site and the cobalamin-binding domains (previously determined) provide a starting point for understanding the methyl transfer reactions of methionine synthase...
  49. pmc Crystal structure of coproporphyrinogen III oxidase reveals cofactor geometry of Radical SAM enzymes
    Gunhild Layer
    Institute of Microbiology, Technical University Braunschweig, Spielmannstrasse 7, D 38106 Braunschweig, Germany
    EMBO J 22:6214-24. 2003
    ..The structure of HemN reveals the cofactor geometry required for Radical SAM catalysis and sets the stage for the development of inhibitors with antibacterial function due to the uniquely bacterial occurrence of the enzyme...
  50. ncbi Interactions of the Escherichia coli methionine repressor with the metF operator and with its corepressor, S-adenosylmethionine
    I Saint-Girons
    J Biol Chem 261:10936-40. 1986
    ..Equilibrium dialysis experiments showed that the met aporepressor binds 2 mol of S-adenosylmethionine per mol of dimer with a dissociation constant of 200 microM...
  51. pmc Natural variability in S-adenosylmethionine (SAM)-dependent riboswitches: S-box elements in bacillus subtilis exhibit differential sensitivity to SAM In vivo and in vitro
    Jerneja Tomsic
    Department of Microbiology and The RNA Group, The Ohio State University, Columbus, Ohio 43210, USA
    J Bacteriol 190:823-33. 2008
    ..A wide range of responses to SAM were observed for the 11 S-box-regulated transcriptional units in Bacillus subtilis, demonstrating that S-box riboswitches can be calibrated to different physiological requirements...
  52. pmc The yggH gene of Escherichia coli encodes a tRNA (m7G46) methyltransferase
    Lara G S De Bie
    Laboratoire de Microbiologie, Universite Libre de Bruxelles, B 1070 Brussels, Belgium
    J Bacteriol 185:3238-43. 2003
    ..Additionally, we generated an E. coli strain with a disrupted yggH gene and show that the mutant strain lacks tRNA (m(7)G46) methyltransferase activity...
  53. pmc Crystal structure of biotin synthase, an S-adenosylmethionine-dependent radical enzyme
    Frederick Berkovitch
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
    Science 303:76-9. 2004
    ..The structure places the substrates between the Fe4S4 cluster, essential for radical generation, and the Fe2S2 cluster, postulated to be the source of sulfur, with both clusters in unprecedented coordination environments...
  54. ncbi Transport of sulfonium compounds. Characterization of the s-adenosylmethionine and s-methylmethionine permeases from the yeast Saccharomyces cerevisiae
    A Rouillon
    Centre de Genetique Moleculaire, CNRS, 91198 Gif sur Yvette, France
    J Biol Chem 274:28096-105. 1999
    ....
  55. ncbi Crystal structure and mechanism of a bacterial fluorinating enzyme
    Changjiang Dong
    Centre for Biomolecular Sciences, The University of St Andrews, Fife KY16 9ST, UK
    Nature 427:561-5. 2004
    ..Both substrate and products have been observed bound to the enzyme, enabling us to propose a nucleophilic substitution mechanism for this biological fluorination reaction...
  56. ncbi Folding of the SAM aptamer is determined by the formation of a K-turn-dependent pseudoknot
    Benoit Heppell
    Departement de Biologie, Faculte des Sciences, Universite de Sherbrooke, Sherbrooke, Quebec, Canada J1K 2R1
    Biochemistry 47:1490-9. 2008
    ..Finally, we show that SAM riboswitch ligand binding is facilitated by the L7Ae K-turn binding protein, which suggests that K-turn motifs may be protein anchor sites used by riboswitches to promote RNA folding...
  57. pmc The x-ray crystal structure of lysine-2,3-aminomutase from Clostridium subterminale
    Bryan W Lepore
    Department of Biochemistry, College of Agricultural and Life Sciences, University of Wisconsin, 1710 University Avenue, Madison, WI 53726, USA
    Proc Natl Acad Sci U S A 102:13819-24. 2005
    ..The chain fold in the central domain is in part analogous to other radical-SAM enzymes...
  58. ncbi Thiamine biosynthesis in Escherichia coli: in vitro reconstitution of the thiazole synthase activity
    Roberta Leonardi
    School of Chemistry, University of Southampton, Southampton SO17 1BJ, United Kingdom
    J Biol Chem 279:17054-62. 2004
    ..The activity is strongly stimulated by the addition of S-adenosylmethionine and NADPH...
  59. ncbi The S(MK) box is a new SAM-binding RNA for translational regulation of SAM synthetase
    Ryan T Fuchs
    Department of Microbiology, The Ohio State University, 484 West 12th Avenue, Columbus, Ohio 43210, USA
    Nat Struct Mol Biol 13:226-33. 2006
    ..The S(MK) box therefore represents a new SAM-binding riboswitch distinct from the previously identified S box RNAs...
  60. pmc The aptamer core of SAM-IV riboswitches mimics the ligand-binding site of SAM-I riboswitches
    Zasha Weinberg
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520 8103, USA
    RNA 14:822-8. 2008
    ..Our findings support the view that RNA has considerable structural versatility and reveal that riboswitches exploit this potential to expand the scope of RNA in genetic regulation...
  61. ncbi Molecular-recognition characteristics of SAM-binding riboswitches
    Jinsoo Lim
    Department of Molecular, Cellular, and Developmental Biology, Yale University, New Haven, CT 06520, USA
    Angew Chem Int Ed Engl 45:964-8. 2006
  62. ncbi N2-methylation of guanosine at position 10 in tRNA is catalyzed by a THUMP domain-containing, S-adenosylmethionine-dependent methyltransferase, conserved in Archaea and Eukaryota
    Jean Armengaud
    Commissariat à l Energie Atomique VALRHO, DSV DIEP SBTN, Service de Biochimie post génomique and Toxicologie Nucléaire, F 30207 Bagnols sur Ceze, France
    J Biol Chem 279:37142-52. 2004
    ..The co-occurrence of these two guanosine dimethyltransferases in both Archaea and Eukaryota but not in Bacteria is a hallmark of distinct tRNAs maturation strategies between these domains of life...
  63. pmc Evidence for a second class of S-adenosylmethionine riboswitches and other regulatory RNA motifs in alpha-proteobacteria
    Keith A Corbino
    Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT 06520 8103, USA
    Genome Biol 6:R70. 2005
    ..Riboswitches are most common in the genomes of low GC Gram-positive bacteria (for example, Bacillus subtilis contains examples of all known riboswitches), and some riboswitch classes seem to be restricted to this group...
  64. ncbi Quantification of serum and urinary S-adenosylmethionine and S-adenosylhomocysteine by stable-isotope-dilution liquid chromatography-mass spectrometry
    Sally P Stabler
    Division of Hematology, Department of Medicine, University of Colorado Health Sciences Center, Denver, CO 80262, USA
    Clin Chem 50:365-72. 2004
    ....
  65. ncbi Structure of protein phosphatase methyltransferase 1 (PPM1), a leucine carboxyl methyltransferase involved in the regulation of protein phosphatase 2A activity
    Nicolas Leulliot
    Institut de Biochimie et de Biophysique Moléculaire et Cellulaire CNRS UMR 8619, Universite Paris Sud, Bat 430, 91405 Orsay, France
    J Biol Chem 279:8351-8. 2004
    ..The structure of PPM1 in a second crystal form provides clues to the dynamic nature of the PPM1/PP2A interaction...
  66. ncbi Cystathionine beta-synthase is coordinately regulated with proliferation through a redox-sensitive mechanism in cultured human cells and Saccharomyces cerevisiae
    Kenneth N Maclean
    Department of Pediatrics, University of Colorado School of Medicine, Denver, Colorado 80262, USA
    J Cell Physiol 192:81-92. 2002
    ..Our data indicates that screening compounds for the ability to affect transsulfuration in cultured cell models must take proliferation status into account to avoid masking regulatory interactions that may be of significance in vivo...
  67. ncbi Presenilin 1 gene silencing by S-adenosylmethionine: a treatment for Alzheimer disease?
    Sigfrido Scarpa
    Dipartimento di Chirurgia P Valdoni, Universita di Roma La Sapienza, Rome, Italy
    FEBS Lett 541:145-8. 2003
    ..Here we report that SAM administration, in human neuroblastoma SK-N-SH cell cultures, downregulates PS1 gene expression and Ab production...
  68. ncbi Alleviation of intrasteric inhibition by the pathogenic activation domain mutation, D444N, in human cystathionine beta-synthase
    Ruby Evande
    Biochemistry Department, University of Nebraska, Lincoln, NE 68588 0664, USA
    Biochemistry 41:11832-7. 2002
    ..e., wild-type enzyme as isolated), "activated" (wild-type enzyme + AdoMet or the D444N mutant as isolated), and superactivated (D444N mutant + AdoMet or wild-type enzyme lacking the C-terminal regulatory domain)...
  69. ncbi Salt stress enhances xylem development and expression of S-adenosyl-L-methionine synthase in lignifying tissues of tomato plants
    Inmaculada Sánchez-Aguayo
    Departamento de Biologia Celular, Facultad de Biologia, Universidad de Sevilla, 41012 Sevilla, Spain
    Planta 220:278-85. 2004
    ....
  70. ncbi The generation of 5'-deoxyadenosyl radicals by adenosylmethionine-dependent radical enzymes
    Joseph T Jarrett
    Department of Biochemistry and Biophysics, University of Pennsylvania, 905B Stellar Chance Laboratory, 422 Curie Boulevard, Philadelphia, PA 19104 6059, USA
    Curr Opin Chem Biol 7:174-82. 2003
    ..The utilization of this radical as a catalytic and stoichiometric oxidant in many different enzyme reactions reflects the broad diversity of radical enzymes throughout biology...
  71. ncbi Structure and function of radical SAM enzymes
    Gunhild Layer
    Divison of Structural Biology, German Research Center for Biotechnology GBF, Mascheroder Weg 1, D 38124 Braunschweig, Germany
    Curr Opin Chem Biol 8:468-76. 2004
    ..Remaining differences emphasize the plasticity of the protein scaffold in functionally accommodating 600 family members...
  72. ncbi S-adenosylmethionine and Pneumocystis
    Salim Merali
    Department of Medical and Molecular Parasitology, New York University School of Medicine, 341 East 25th Street, New York, NY, USA
    FEMS Microbiol Lett 237:179-86. 2004
    ..Preliminary data indicate that deliberate reduction of host lung AdoMet by nicotine treatment is therapeutic in the rat model of Pneumocystis pneumonia...
  73. pmc Discovery and characterization of a marine bacterial SAM-dependent chlorinase
    Alessandra S Eustáquio
    Center for Marine Biotechnology and Biomedicine, Scripps Institution of Oceanography, University of California San Diego, 9500 Gilman Drive, La Jolla, California 92093, USA
    Nat Chem Biol 4:69-74. 2008
    ....
  74. pmc Crystal structure of tRNA(m1G37)methyltransferase: insights into tRNA recognition
    Hyung Jun Ahn
    Structural Proteomics Laboratory, School of Chemistry and Molecular Engineering, Seoul National University, Seoul 151 742, Korea
    EMBO J 22:2593-603. 2003
    ..The C-terminal domain shows structural similarity to trp repressor. We propose a plausible model for the TrmD(2)-tRNA(2) complex, which provides insights into recognition of the general tRNA structure by TrmD...
  75. ncbi DMB (DNMT-magnetic beads) assay: measuring DNA methyltransferase activity in vitro
    Tomoki Yokochi
    Epigenetic Gene Regulation and Cancer Section, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
    Methods Mol Biol 287:285-96. 2004
    ..This DMB assay is simple and easy, has very low background, and, most importantly, is highly reproducible for the precise enzymatic analysis of any DNA methyltransferase in vitro...
  76. ncbi An mRNA structure that controls gene expression by binding S-adenosylmethionine
    Wade C Winkler
    Department of Molecular, Cellular and Developmental Biology, Yale University, PO Box 208103, New Haven, Connecticut 06520 8103, USA
    Nat Struct Biol 10:701-7. 2003
    ..This and related findings indicate that direct interaction between small metabolites and allosteric mRNAs is an important and widespread form of genetic regulation in bacteria...
  77. ncbi S-Adenosylmethionine: molecular, biological, and clinical aspects--an introduction
    Charles S Lieber
    Section of Liver Disease and Nutrition, Bronx VA Medical Center, Mount Sinai School of Medicine, NY 10468, USA
    Am J Clin Nutr 76:1148S-50S. 2002
    ..This symposium reviewed the biological and corresponding molecular aspects of SAMe metabolism and the clinical consequences of its deficiency or supplementation in various tissues...
  78. ncbi Deep knot structure for construction of active site and cofactor binding site of tRNA modification enzyme
    Osamu Nureki
    Department of Biotechnology, Faculty of Engineering, Ehime University, Matsuyama 790 8577, Japan
    Structure 12:593-602. 2004
    ..Based on Gua18 modeling onto the active site, we propose that once Gua18 binds, the phosphate group activates Arg41, which then deprotonates the 2'-OH group for methylation...
  79. ncbi Methionine metabolism in plants: chloroplasts are autonomous for de novo methionine synthesis and can import S-adenosylmethionine from the cytosol
    Stéphane Ravanel
    Departement de Reponse et Dynamique Cellulaires, CEA Grenoble, 17 rue des Martyrs, 38054 Grenoble Cedex 9, France
    J Biol Chem 279:22548-57. 2004
    ..Therefore, the chloroplastic AdoMet carrier serves as a link between cytosolic and chloroplastic one-carbon metabolism...
  80. ncbi Specificity and mechanism of RNA cap guanine-N2 methyltransferase (Tgs1)
    Stephane Hausmann
    Molecular Biology Program, Sloan Kettering Institute, New York, New York 10021, USA
    J Biol Chem 280:4021-4. 2005
    ..We conclude that Tgs1 is guanine-specific, that N7 methylation must precede N2 methylation, that Tgs1 acts via a distributive mechanism, and that the chemical steps of TMG synthesis do not require input from RNA or protein cofactors...
  81. ncbi Binding of adenosine-based ligands to the MjDim1 rRNA methyltransferase: implications for reaction mechanism and drug design
    Heather C O'Farrell
    Department of Physiology and Biophysics, Virginia Commonwealth University, Richmond, Virginia 23298 0133, USA
    Biochemistry 49:2697-704. 2010
    ..We also discuss the inability thus far to determine a structure of a target adenosine bound in its active site...
  82. ncbi Structure of the S-adenosylmethionine riboswitch regulatory mRNA element
    Rebecca K Montange
    Nature 441:1172-5. 2006
    ..Ligand binding induces the formation of a series of tertiary interactions with one of the helices, serving as a communication link between the aptamer and expression platform domains...
  83. ncbi S-adenosylmethionine and Pneumocystis carinii
    S Merali
    Department of Medical and Molecular Parasitology, New York University School of Medicine, New York, New York 10010, USA
    J Biol Chem 275:14958-63. 2000
    ..carinii in the lungs. These findings demonstrate that P. carinii is an AdoMet auxotroph. The uptake and metabolism of this compound are rational chemotherapeutic targets...
  84. pmc The Gcd10p/Gcd14p complex is the essential two-subunit tRNA(1-methyladenosine) methyltransferase of Saccharomyces cerevisiae
    J Anderson
    Laboratory of Eukaryotic Gene Regulation, National Institute of Child Health and Human Development, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 97:5173-8. 2000
    ..Our results provide a demonstration of a two-component tRNA MTase and suggest that binding of AdoMet and tRNA substrates depends on different subunits of the complex...
  85. ncbi Three-dimensional crystal structures of Escherichia coli met repressor with and without corepressor
    J B Rafferty
    Astbury Department of Biophysics, University of Leeds, UK
    Nature 341:705-10. 1989
    ..We propose that the interaction of met repressor with DNA occurs through either a pair of symmetry-related alpha-helices or a pair of beta-strands, and suggest a model for binding of several dimers to met operator regions...
  86. ncbi The 2.2 A structure of the rRNA methyltransferase ErmC' and its complexes with cofactor and cofactor analogs: implications for the reaction mechanism
    G Schluckebier
    Abbott Laboratories, D46Y AP 10, 100 Abbott Park Road, Abbott Park, IL, 60064, USA
    J Mol Biol 289:277-91. 1999
    ..A model for the transition-state based on the atomic details of the active site is consistent with a one-step methyl-transfer mechanism and might serve as a first step towards the design of potent Erm inhibitors...
  87. ncbi B-vitamin deprivation induces hyperhomocysteinemia and brain S-adenosylhomocysteine, depletes brain S-adenosylmethionine, and enhances PS1 and BACE expression and amyloid-beta deposition in mice
    Andrea Fuso
    Department of Surgery P Valdoni, Sapienza University of Rome, Italy
    Mol Cell Neurosci 37:731-46. 2008
    ..Collectively, these findings are consistent with the hypothesis that abnormal methylation in association with hyperhomocysteinemia may contribute to Alzheimer's disease...
  88. ncbi S-adenosylmethionine as an oxidant: the radical SAM superfamily
    Susan C Wang
    Department of Biochemistry, University of Wisconsin Madison, 1710 University Avenue, Madison, WI 53726, USA
    Trends Biochem Sci 32:101-10. 2007
    ..Recent results are beginning to determine the unique biochemistry for some of the radical SAM enzymes, for example, lysine 2,3 aminomutase, pyruvate formate lyase activase and biotin synthase...
  89. pmc Metabolic derangement of methionine and folate metabolism in mice deficient in methionine synthase reductase
    C Lee Elmore
    Life Sciences Institute, University of Michigan, Ann Arbor, MI, USA
    Mol Genet Metab 91:85-97. 2007
    ..The different metabolite profiles in the various genetic mouse models for hyperhomocyst(e)inemia may be useful in understanding biological effects of elevated homocyst(e)ine...
  90. ncbi Reversed-phase high-performance liquid chromatography procedure for the simultaneous determination of S-adenosyl-L-methionine and S-adenosyl-L-homocysteine in mouse liver and the effect of methionine on their concentrations
    W Wang
    Department of Pathology, Medical College of Ohio, Toledo 43614-5806, USA
    J Chromatogr B Biomed Sci Appl 762:59-65. 2001
    ..This indicated that methionine was promptly converted to SAM and then rapidly catabolized into SAH. Thus, the metabolism of methionine to SAM should be considered in the supplementation of methionine to maintain SAM levels in the body...
  91. ncbi Crystal structure of the radical SAM enzyme catalyzing tricyclic modified base formation in tRNA
    Yoko Suzuki
    Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, B34 4259 Nagatsuta cho, Midori ku, Yokohama shi, Kanagawa 226 8501, Japan
    J Mol Biol 372:1204-14. 2007
    ..Mutational analyses in yeast supported the validity of this complex model structure, which provides a structural insight into the radical reaction involving two [4Fe-4S] clusters to create a complex tricyclic base...
  92. pmc A universal competitive fluorescence polarization activity assay for S-adenosylmethionine utilizing methyltransferases
    Tiffany L Graves
    Department of Pharmaceutical Sciences, Biomanufacturing Research Institute and Technology Enterprise, North Carolina Central University, Durham, NC 27707, USA
    Anal Biochem 373:296-306. 2008
    ..The IC(50) value obtained using a selective COMT inhibitor was consistent with previously published data. Thus, this sensitive and homogeneous assay is amenable for screening compounds for inhibitors of methyltransferase activity...
  93. pmc Crystal structures of the SAM-III/S(MK) riboswitch reveal the SAM-dependent translation inhibition mechanism
    Changrui Lu
    Department of Molecular Biology and Genetics, Cornell University, 251 Biotechnology Building, Ithaca, New York 14853, USA
    Nat Struct Mol Biol 15:1076-83. 2008
    ..We captured a structural snapshot of the S(MK) box riboswitch sampling the near-cognate ligand S-adenosyl-L-homocysteine (SAH) in which SAH was found to adopt an alternative conformation and fails to make several key interactions...
  94. pmc Control of radical chemistry in the AdoMet radical enzymes
    Kaitlin S Duschene
    Department of Chemistry and Biochemistry, Montana State University, Bozeman, 59717, United States
    Curr Opin Chem Biol 13:74-83. 2009
    ....
  95. pmc Anaerobic functionalization of unactivated C-H bonds
    Squire J Booker
    Department of Chemistry, The Pennsylvania State University, University Park, 16802, United States
    Curr Opin Chem Biol 13:58-73. 2009
    ..In addition to surveying reactions that have been studied at various levels of detail, this review will speculate on the mechanisms of other types of reactions that this chemistry lends itself to...
  96. ncbi The mechanism of DNA cytosine-5 methylation. Kinetic and mutational dissection of Hhai methyltransferase
    G Vilkaitis
    Institute of Biotechnology, Laboratory of Biological DNA Modification, LT-2028 Vilnius, Lithuania
    J Biol Chem 276:20924-34. 2001
    ..In contrast to previous reports, our results imply a random substrate binding order mechanism for M.HhaI...
  97. ncbi Comparison of protein structures reveals monophyletic origin of the AdoMet-dependent methyltransferase family and mechanistic convergence rather than recent differentiation of N4-cytosine and N6-adenine DNA methylation
    J M Bujnicki
    Molecular Biology Research Program, Henry Ford Health System, One Ford Place, Suite 5D Detroit, MI 48202, USA
    In Silico Biol 1:175-82. 1999
    ..Such evolutionary analysis of methyltransferases has never been published yet in the literature and will guide further phylogenetical studies based on both sequence and structure comparison...
  98. pmc Functional studies of [FeFe] hydrogenase maturation in an Escherichia coli biosynthetic system
    Paul W King
    Basic Sciences Center, NREL, Golden, CO 80401, USA
    J Bacteriol 188:2163-72. 2006
    ..Together, these results demonstrate that the catalytic domain and a functionally complete set of Hyd maturation proteins are fundamental to achieving biosynthesis of catalytic [FeFe] hydrogenases...
  99. ncbi An in vitro screening method for DNA cytosine-C5-methylase inhibitor
    Takashi Tamura
    Department of Bioresources Chemistry, Faculty of Agriculture, Okayama University, Japan
    Nat Prod Lett 16:25-7. 2002
    ..Our method uses a commercially available Hae III methylase (cytosine C5 methylase), its corresponding Hae III endonuclease, and lambda DNA as their substrate...
  100. pmc Natural history of S-adenosylmethionine-binding proteins
    Piotr Z Kozbial
    Stowers Institute for Medical Research, Kansas City, MO 64110, USA
    BMC Struct Biol 5:19. 2005
    ..We addressed this issue by computational comparison of sequences and structures of various S-adenosylmethionine-binding proteins...
  101. ncbi Biochemistry: biosynthesis of an organofluorine molecule
    David O'Hagan
    School of Chemistry and Centre for Biomolecular Sciences, University of St Andrews, North Haugh, St Andrews, Fife KY16 9ST, UK
    Nature 416:279. 2002
    ..To our knowledge, this is the first fluorinase enzyme to be identified, a discovery that opens up a new biotechnological opportunity for the preparation of organofluorine compounds...

Research Grants63

  1. Role of SAMe on UBC9 and sumolyation in liver cancer and alcoholic liver injury
    Maria Lauda Tomasi; Fiscal Year: 2012
    ..Three aims are proposed in this application to test these hypotheses and elucidate how SAMe affects signaling pathways that are important in hepatocarcinogenesis and development of alcoholic liver injury. ..
  2. Prospective studies of cancer etiology and prevention in Shanghai and Singapore
    Jian Min Yuan; Fiscal Year: 2013
    ..The findings of the proposed study will have great impact on reducing incidence and mortality of lung and liver cancers in humans. ..
  3. Role of Polyamines in MYCN-Amplified Neuroblastoma
    ANDRE BACHMANN; Fiscal Year: 2009
    ..Our research will be useful in the development of novel treatments for the most aggressive forms of the childhood cancer neuroblastoma. ..
  4. The mechanisms by which alcohol and HIV render the lung susceptible to injury
    DAVID MARSHALL GUIDOT; Fiscal Year: 2013
    ..This research project is designed to determine how alcohol and HIV-1 interact to make the lung susceptible to injury, and to develop effective treatments that can improve the health of these vulnerable individuals. ..
  5. Genistein and Prostate Cancer
    Rajvir Dahiya; Fiscal Year: 2010
    ....
  6. Folate and S-adenosyimethionine in Methyl Group and One-carbon Metabolism
    Conrad Wagner; Fiscal Year: 2012
    ....
  7. Role of ALDH7A1 in Ethanol-Induced Oxidative Damage
    CHAD NICHOLAS BROCKER; Fiscal Year: 2011
    ..This long term goal of this project is to elucidate the protective functions of ALDH7A1 during excessive alcohol consumption. ..
  8. ROLE OF SAMe IN LIVER FUNCTION AND INJURY
    SHELLY CHI LOO LU; Fiscal Year: 2012
    ..The goal of this project is to understand how SAMe controls these processes and how injury and cancer occur when SAMe metabolism is perturbed. ..
  9. A Novel Murine Model of Chronic Inflammatory Periodontitus
    Helieh S Oz; Fiscal Year: 2010
    ..Specific aims for this proposal will examine targeted antioxidant therapies using mouse models of oral disease as a potential strategy for adjunctive management of human periodontitis. ..
  10. DYSREGULATION OF GSH SYNTHESIS DURING LIVER INJURY AND FIBROSIS
    SHELLY CHI LOO LU; Fiscal Year: 2013
    ....
  11. EFFECT OF DRUGS OF ABUSE ON NEURONAL REDOX AND METHYLATION STATUS
    Richard C Deth; Fiscal Year: 2012
    ..The results will provide an entirely new way of thinking about how drugs of abuse affect the brain and could lead to improved ways to treatment to treat drug addiction. ..
  12. Structure and Mechanism of SAM-responsive Riboswitches
    Robert T Batey; Fiscal Year: 2013
    ..A deeper knowledge of how RNA specifically interacts with small molecules will help pave the way for a new generation of therapeutics that target non-protein coding RNAs that are pervasive in both bacteria and eukaryotes. ..
  13. MAMMALIAN POLYAMINE METABOLISM
    David J Feith; Fiscal Year: 2013
    ..The successful completion of these studies will lead to a more complete understanding of polyamine function in epithelial carcinogenesis and will enhance future development of polyamine-targeted therapies to prevent and treat cancer. ..
  14. Polyamine Metabolism in Leishmania
    Buddy Ullman; Fiscal Year: 2013
    ..donovani polyamine pathway. ..
  15. Role of MAT and SAMe in Colon Cancer Pathogenesis and Treatment
    SHELLY CHI LOO LU; Fiscal Year: 2012
    ..abstract_text> ..
  16. Epigenetic regulation of alcoholic steatohepatitis in a mouse model
    CHARLES HOPKINSON HALSTED; Fiscal Year: 2012
    ....
  17. Diphthamide biosynthesis
    Hening Lin; Fiscal Year: 2012
    ....
  18. Homocysteine, Adiponectin, and Alcoholic Liver Disease
    Zhenyuan Song; Fiscal Year: 2013
    ..We will use the state-of-the-art technologies to investigate this clinically relevant process. ..
  19. NYU Lung Cancer Biomarker Center
    William N Rom; Fiscal Year: 2013
    ..Importantly, we will cross validate biomarker panels in the same prospective high risk smoker cohorts. ..
  20. Development Of An Eye Drop To Treat Presbyopia
    William H Garner; Fiscal Year: 2012
    ..Encore Vision's goal is to develop a safe topical ocular drop as an option for the treatment of presbyopia. ..
  21. Hepatic Steatosis and the Lipid Metabolome
    GHULAM A S ANSARI; Fiscal Year: 2012
    ..This project will identify biomarkers of fatty liver for an early diagnosis, and also potential targets for the development of new drugs to prevent ALD and perhaps NAFLD. ..
  22. Hyperhomocysteinemia, S-adenosylhomocysteine Accumulation, and Epigenetics
    Warren D Kruger; Fiscal Year: 2013
    ..Achieving these aims will lead to understanding the mechanism by which elevated tHcy causes disease and will give us new insight into potential interventions that could delay or eliminate the onset of homocysteine related diseases. ..
  23. Gene-Nutrient Interactions in Neural Tube Defects
    Patrick J Stover; Fiscal Year: 2012
    ..abstract_text> ..
  24. Polyamine and trypanothione metabolism in Trypanosoma brucei
    Margaret A Phillips; Fiscal Year: 2013
    ....
  25. REGULATION OF METHIONINE METABOLISM IN BACILLUS SUBTILIS
    Tina M Henkin; Fiscal Year: 2013
    ..The goal of this project is to investigate the molecular mechanisms underlying RNA-mediated ligand recognition and gene regulation in response to modulation of RNA structure. ..
  26. REGULATION AND FUNCTIONS OF METHIONINE ADENOSYLTRANSFERASE GENES IN LIVER
    SHELLY CHI LOO LU; Fiscal Year: 2013
    ....
  27. Dietary Folate: Impact on Prostate Tumor Biology, Genetics and Epigenetics
    DOMINIC JAMES SMIRAGLIA; Fiscal Year: 2010
    ..If so, this could have very important implications for prostate cancer in men allowing us to slow the progression in men showing the very first signs of prostate cancer and therefore significantly reducing mortality from this disease. ..
  28. FASEB SRC on Biological Methylation: From DNA and Histones to Disease
    Paul A Wade; Fiscal Year: 2012
    ..Approximately 150 scientists will attend to coordinate, exchange, and disseminate information on the underlying mechanisms controlling epigenetic methylation and to explore the contribution of dysregulated methylation to human disease. ..
  29. Alcohol abuse, oxidative stress, and zinc deficiency in lung disease
    Ashish J Mehta; Fiscal Year: 2013
    ....
  30. Targeting Trypanosoma brucei S-adenosylmethionine decarboxylase in Drug Discovery
    NAHIR VELEZ; Fiscal Year: 2012
    ..The work described in this proposal characterizes an essential enzyme that has unique features in the parasite, with the goal of developing new chemotherapeutic agents against this devastating disease. ..
  31. Methionine Adenosyltransferase as a Therapeutic Target for Liver Fibrosis
    Komal Ramani; Fiscal Year: 2013
    ..My long term plan is to establish myself as an independent Investigator in the field of human liver fibrosis and cirrhosis. ..
  32. 2010 FASEB Conference "Biological Methylation:From DNA to Histones and Beyond"
    Paula M Vertino; Fiscal Year: 2010
    ..Approximately 150 scientists will attend to coordinate, exchange, and disseminate information on the underlying mechanisms controlling epigenetic methylation and to explore the contribution of dysregulated methylation to human disease. ..
  33. Integration of S-adenosylmethionine Metabolism with Epigenetics and Cell Cycle
    Stacey Borrego; Fiscal Year: 2013
    ..My thesis proposal will only begin to address nutrient imbalance as a factor of epigenetic changes. However, I will develop tools to allow others to expand research on the interaction between nutrients and epigenetics. ..
  34. Immune enhancement for immunological non-responders to ART
    DAVID MARSHALL GUIDOT; Fiscal Year: 2013
    ....
  35. Wilson Disease: Regulation of Steatosis by Methionine Metabolism
    Valentina Medici; Fiscal Year: 2013
    ..The study will also provide insights into the role of copper and methionine metabolism in more common diseases, such as non-alcoholic fatty liver disease. ..
  36. Targeting S-adenosylmethionine decarboxylase for HAT drug discovery
    Margaret A Phillips; Fiscal Year: 2013
    ....
  37. Biomarkers of Methionine Metabolism and Risk for Colorectal Adenoma
    Martha J Shrubsole; Fiscal Year: 2010
    ....
  38. Methyltransferease sensors for homogenous HTS assays
    Jeremy S Paige; Fiscal Year: 2012
    ..This project will develop a simple, homogenous fluorescence assay that can be applied to any MT, enabling large-scale HTS for MT inhibitors. ..
  39. Methionine Adenosyltransferase as a Therapeutic Target for Liver Fibrosis
    Komal Ramani; Fiscal Year: 2010
    ....
  40. The Enzymology of Phosphonate Metabolism
    Frank M Raushel; Fiscal Year: 2013
    ....
  41. Homocysteine &Heme: A Role in Thrombosis?
    Jan P Kraus; Fiscal Year: 2012
    ..abstract_text> ..
  42. Co(II)-Radical Pair Dynamics in B12 Enzyme Catalysis
    Kurt Warncke; Fiscal Year: 2012
    ....
  43. Effect of Alcohol on Hepatic Creatine Biosynthesis: Role of Defective Methylation
    Kusum K Kharbanda; Fiscal Year: 2013
    ....
  44. Mechanistic Investigation of the Radical SAM Deaminase Desll
    Mark W Ruszczycky; Fiscal Year: 2010
    ..Their characterization provides the foundation necessary for the development of effective antibiotics ..
  45. An Activity-Based Assay to Screen for PRMT1 Inhibitors
    Kerri A Mowen; Fiscal Year: 2013
    ..Since aberrant PRMT1 activity has been associated with cardiovascular, malignant, infectious, and autoimmune disease, it may be a viable therapeutic target for several indications. ..
  46. Mechanisms of Alcohol-Induced Immunosuppression
    Shirish S Barve; Fiscal Year: 2010
    ..Moreover, the data from these studies would support our future goals by providing a basis for relevant clinical paradigms for the development of potential therapeutic intervention(s) for alcoholic patients. ..
  47. Novel resveratrol analogs and colorectal cancer treatment
    Chunming Liu; Fiscal Year: 2013
    ....
  48. Structure, Function and Conformational Dynamics of the Ste14p Methyltransferase
    Christine A Hrycyna; Fiscal Year: 2013
    ....
  49. Understanding hydrogen atom transfer reactions in enzymes
    E NEIL MARSH; Fiscal Year: 2013
    ..A better understanding of these enzymes may help in the design of drugs to fight diseases such as cancer and arthritis, and in engineering micro-organisms to clean up toxic chemicals in the environment. ..
  50. DIET METHIONINE--S-ADO, POLYAMINES AND MAMMARY TUMORS
    ERVIN HAWRYLEWICZ; Fiscal Year: 1993
    ..Tumor burden will be related to metabolic pathway, animal model and dietary protein-casein concentration...
  51. S-Adenosylmethionine and Pneumocystis treatment
    Salim Merali; Fiscal Year: 2010
    ..We will also determine the relative importance to Pneumocystis of AdoMet obtained from lungs and from the entire extracellular pool. ..
  52. Rational Design of Inhibitors of Polyamine Synthesis
    Steven Ealick; Fiscal Year: 2007
    ..An external committee with expertise in clinical oncology will advise us on project priorities and potential clinical trials. ..
  53. Battling AIDS via Mechanistic Understanding of the tRNA Phe modification enzyme T
    Lei Li; Fiscal Year: 2013
    ..The revealed structure of "X" could additionally shed light on the reaction mechanism of TYW1, which will be tested in this proposal as well as in the future investigations after the R21 grant period. ..
  54. CONTROL OF EUCARYOTIC FUNCTION BY METHYLATION
    Steven Clarke; Fiscal Year: 2009
    ..abstract_text> ..
  55. Mechanisms of Radical-Dependent Biological Methylation
    Squire J Booker; Fiscal Year: 2013
    ..We will characterize this reaction further using a variety of kinetic, spectroscopic, and biochemical techniques, and provide biochemical and/or structural evidence for each of the postulated intermediates in the reaction. ..
  56. S-Adenosylmethionine and Pneumocystis treatment
    Salim Merali; Fiscal Year: 2009
    ..Completion of these Aims will lay the groundwork for developing the nicotine or nicotine analogues as sole or adjunctive therapy for PCP. ..
  57. Catalytic Mechanism of Biotin Synthase
    JOSEPH JARRETT; Fiscal Year: 2007
    ..abstract_text> ..
  58. ABNORMAL METABOLISM IN ALCOHOLIC CIRRHOSIS
    Rajender Chawla; Fiscal Year: 1993
    ..This may be partly due to cysteine and choline deficiencies identified by us. In addition, these patients may be at a greater risk to develop hepatomas since choline deficient diets by themselves act as carcinogens...
  59. Modulation of DNA methylation status by dietary zinc: role in cancer prevention
    LOUISE FONG; Fiscal Year: 2009
    ..In addition, the results will identify targets for chemoprevention, diagnosis, and treatment of this deadly cancer. ..
  60. TRANSPORT OF S-ADENOSYLMETHIONINE IN RICKETTSIA
    David Wood; Fiscal Year: 2002
    ..Completion of these studies will contribute to our understanding of how this pathogen exploits the intracellular niche as well as provide insight into rickettsial evolution. ..
  61. L-DOPA OVERLOAD: MECHANISMS FOR THE SIDE EFFECTS.
    CLIVEL GEORGE CHARLTON; Fiscal Year: 2010
    ..abstract_text> ..
  62. T LYMPHOCYTE DIFFERENTIATION:ROLE OF ADENOXYLMETHIONINE
    Malak Kotb; Fiscal Year: 1992
    ....
  63. Carcinogenesis: Effects of Diet Deficient in Methyl Donors
    Shi Huang; Fiscal Year: 2007
    ..The new understanding that will emerge from these studies will help clarify the role of nutrient metabolism in carcinogenesis. The results may have important public health implications. ..