methionine trna ligase

Summary

Summary: An enzyme that activates methionine with its specific transfer RNA. EC 6.1.1.10.

Top Publications

  1. ncbi Arc1p organizes the yeast aminoacyl-tRNA synthetase complex and stabilizes its interaction with the cognate tRNAs
    K Deinert
    Biochemie Zentrum Heidelberg BZH, University of Heidelberg, Im Neuenheimer Feld 328, D 69120 Heidelberg, Germany
    J Biol Chem 276:6000-8. 2001
  2. pmc The intracellular location of two aminoacyl-tRNA synthetases depends on complex formation with Arc1p
    K Galani
    Biochemie Zentrum Heidelberg, Im Neuenheimer Feld 328, D 69120 Heidelberg, Germany
    EMBO J 20:6889-98. 2001
  3. ncbi The tRNA aminoacylation co-factor Arc1p is excluded from the nucleus by an Xpo1p-dependent mechanism
    Kyriaki Galani
    Biochemie Zentrum Heidelberg, Im Neuenheimer Feld 328, D 69120 Heidelberg, Germany
    FEBS Lett 579:969-75. 2005
  4. pmc The yeast protein Arc1p binds to tRNA and functions as a cofactor for the methionyl- and glutamyl-tRNA synthetases
    G Simos
    University of Heidelberg, Institut fur Biochemie I, Germany
    EMBO J 15:5437-48. 1996
  5. ncbi Specific sequence homology and three-dimensional structure of an aminoacyl transfer RNA synthetase
    T Webster
    Science 226:1315-7. 1984
  6. ncbi Aminoacyl-tRNA synthetase complexes: beyond translation
    Sang Won Lee
    National Creative Research Initiatives Center for ARS Network, College of Pharmacy, Seoul National University, Seoul 151 742, Korea
    J Cell Sci 117:3725-34. 2004
  7. ncbi Role of 5SrRNA as a positive effector of some aminoacyl-tRNA synthetases in macromolecular complexes, with specific reference to methionyl-tRNA synthetase
    K Ogata
    Institute for Gene Expression, Dobashi Kyoritu Hospital, Ehime
    J Biochem 110:1037-44. 1991
  8. ncbi Cloning of a human cDNA encoding a protein with high homology to yeast methionyl-tRNA synthetase
    H Lage
    Institute of Pathology, Charite, Humboldt University Berlin, Germany
    Gene 178:187-9. 1996
  9. ncbi Pharmacophore-based virtual screening: the discovery of novel methionyl-tRNA synthetase inhibitors
    Su Yeon Kim
    Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, Republic of Korea
    Bioorg Med Chem Lett 16:4898-907. 2006
  10. ncbi The 2.0 A crystal structure of Thermus thermophilus methionyl-tRNA synthetase reveals two RNA-binding modules
    I Sugiura
    Department of Chemistry, Faculty of Science, Ochanomizu University, Otsuka, Bunkyo ku, 112 8610, Japan
    Structure 8:197-208. 2000

Scientific Experts

Detail Information

Publications152 found, 100 shown here

  1. ncbi Arc1p organizes the yeast aminoacyl-tRNA synthetase complex and stabilizes its interaction with the cognate tRNAs
    K Deinert
    Biochemie Zentrum Heidelberg BZH, University of Heidelberg, Im Neuenheimer Feld 328, D 69120 Heidelberg, Germany
    J Biol Chem 276:6000-8. 2001
    ....
  2. pmc The intracellular location of two aminoacyl-tRNA synthetases depends on complex formation with Arc1p
    K Galani
    Biochemie Zentrum Heidelberg, Im Neuenheimer Feld 328, D 69120 Heidelberg, Germany
    EMBO J 20:6889-98. 2001
    ..We suggest that the organization of aminoacyl-tRNA synthetases into a multimeric complex not only affects catalysis, but is also a means of segregating the tRNA- aminoacylation machinery mainly to the cytoplasmic compartment...
  3. ncbi The tRNA aminoacylation co-factor Arc1p is excluded from the nucleus by an Xpo1p-dependent mechanism
    Kyriaki Galani
    Biochemie Zentrum Heidelberg, Im Neuenheimer Feld 328, D 69120 Heidelberg, Germany
    FEBS Lett 579:969-75. 2005
    ..Thus, the cytoplasmic location of Arc1p is maintained by Xpo1p-dependent nuclear export and Arc1p could act as an adapter in the nucleocytoplasmic trafficking of tRNA and/or the tRNA-aminoacylation machinery...
  4. pmc The yeast protein Arc1p binds to tRNA and functions as a cofactor for the methionyl- and glutamyl-tRNA synthetases
    G Simos
    University of Heidelberg, Institut fur Biochemie I, Germany
    EMBO J 15:5437-48. 1996
    ..Arc1p is, therefore, a yeast protein with dual specificity: it associates with tRNA and aminoacyl-tRNA synthetases. This functional interaction may be required for efficient aminoacylation in vivo...
  5. ncbi Specific sequence homology and three-dimensional structure of an aminoacyl transfer RNA synthetase
    T Webster
    Science 226:1315-7. 1984
    ..The three synthetases probably fold identically in this region...
  6. ncbi Aminoacyl-tRNA synthetase complexes: beyond translation
    Sang Won Lee
    National Creative Research Initiatives Center for ARS Network, College of Pharmacy, Seoul National University, Seoul 151 742, Korea
    J Cell Sci 117:3725-34. 2004
    ..They may thus have joined the ARS community to coordinate protein synthesis with other biological processes...
  7. ncbi Role of 5SrRNA as a positive effector of some aminoacyl-tRNA synthetases in macromolecular complexes, with specific reference to methionyl-tRNA synthetase
    K Ogata
    Institute for Gene Expression, Dobashi Kyoritu Hospital, Ehime
    J Biochem 110:1037-44. 1991
    ..Northern blot analysis of RNA in the immunoprecipitate prepared from the liver supernatant incubated with the antibody against L5 indicated that 5SrRNA was complexed with L5.(ABSTRACT TRUNCATED AT 250 WORDS)..
  8. ncbi Cloning of a human cDNA encoding a protein with high homology to yeast methionyl-tRNA synthetase
    H Lage
    Institute of Pathology, Charite, Humboldt University Berlin, Germany
    Gene 178:187-9. 1996
    ..Northern blotting analysis of total RNA extracted from human gastric carcinoma cells demonstrated a single band with a mobility corresponding to a size of 3.0 kb...
  9. ncbi Pharmacophore-based virtual screening: the discovery of novel methionyl-tRNA synthetase inhibitors
    Su Yeon Kim
    Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, Republic of Korea
    Bioorg Med Chem Lett 16:4898-907. 2006
    ..In this study, potent lead compounds with a novel skeleton, including compound 27 with IC50 = 237 nM, were successfully identified as Escherichia coli MetRS inhibitors...
  10. ncbi The 2.0 A crystal structure of Thermus thermophilus methionyl-tRNA synthetase reveals two RNA-binding modules
    I Sugiura
    Department of Chemistry, Faculty of Science, Ochanomizu University, Otsuka, Bunkyo ku, 112 8610, Japan
    Structure 8:197-208. 2000
    ..The class I synthetases are further divided into three subclasses, a, b and c, according to sequence homology. No conserved structural features for tRNA recognition by class I synthetases have been established...
  11. ncbi Arc1p is required for cytoplasmic confinement of synthetases and tRNA
    Marie Pierre Golinelli-Cohen
    Laboratoire d Enzymologie et Biochimie Structurales, Centre National de la Recherche Scientifique, 1 Avenue de la Terrasse, Gif sur Yvette 91190, France
    Mol Cell Biochem 300:47-59. 2007
    ..Our results are consistent with a model according to which Arc1p is a bifunctional protein involved in the subcellular localization of ScMetRS and ScGluRS via its N-terminal domain and of tRNA via its C-terminal domain...
  12. pmc A study of communication pathways in methionyl- tRNA synthetase by molecular dynamics simulations and structure network analysis
    Amit Ghosh
    Molecular Biophysics Unit, Indian Institute of Science, Bangalore 560012, India
    Proc Natl Acad Sci U S A 104:15711-6. 2007
    ..The method developed here also could be used to investigate any protein system where the function takes place through long-distance communication...
  13. ncbi Reconstitution of yeast translation initiation
    Michael G Acker
    Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
    Methods Enzymol 430:111-45. 2007
    ..1998; Trachsel et al., 1977). The following describes methods for synthesizing and purifying the components of the yeast initiation system and assays useful for its characterization...
  14. ncbi An operational RNA code for faithful assignment of AUG triplets to methionine
    Thomas E Jones
    Barcelona Institute for Research in Biomedicine, Barcelona Science Park, C Samitier 1 5, Barcelona 08015, Catalonia, Spain
    Mol Cell 29:401-7. 2008
    ..Thus, in certain species, the fidelity of translation of methionine codons requires a discrimination mechanism that is independent of the information contained in the anticodon...
  15. ncbi Identification of novel inhibitors of methionyl-tRNA synthetase (MetRS) by virtual screening
    John Finn
    Trius Therapeutics, R and D, 6310 Nancy Ridge Drive, Suite 101, San Diego, CA 92121, USA
    Bioorg Med Chem Lett 18:3932-7. 2008
    ..aureus MetRS structure and this information was used to select compounds for testing. This resulted in a high hit rate of compounds that are in distinct structural classes from the known MetRS ligands...
  16. ncbi Methionyl-tRNA synthetase zinc binding domain. Three-dimensional structure and homology with rubredoxin and gag retroviral proteins
    D Fourmy
    Laboratoire de Biochimie, URA 240 CNRS Ecole Polytechnique, Palaiseau, France
    J Mol Biol 231:1078-89. 1993
    ..The solution structure of the zinc binding peptide shows significant discrepancies with the crystal structure of methionyl-tRNA synthetase...
  17. ncbi How methionyl-tRNA synthetase creates its amino acid recognition pocket upon L-methionine binding
    L Serre
    Centre de Biophysique Moleculaire, Centre National de la Recherche Scientifique, rue Charles Sadron, Orleans cedex 2, 45071, France
    J Mol Biol 306:863-76. 2001
    ..The structure of this complex supports a plausible mechanism for the selection of L-methionine versus L-homocysteine and suggests the possibility of information transfer between the different functional domains of the enzyme...
  18. ncbi Yeast cytoplasmic and mitochondrial methionyl-tRNA synthetases: two structural frameworks for identical functions
    B Senger
    UPR n degrees 9002 du CNRS, , 15, , Strasbourg Cedex, 67084, France
    J Mol Biol 311:205-16. 2001
    ..Both MetRSs catalyzed homocysteine editing and aminoacylation of coenzyme A in vitro. Thus, identical synthetic and editing functions can be carried out in different structural frameworks of cytoplasmic and mitochondrial MetRSs...
  19. ncbi Analysis of protein sequences and protein complexes by matrix-assisted laser desorption/ionization mass spectrometry
    M Belghazi
    , Talence, France
    Proteomics 1:946-54. 2001
    ..The spectral suppression phenomenon occurring for complex peptide mixtures analysed by MALDI is discussed, as well as the role of post-source decay analysis for confident protein identification...
  20. ncbi The appended C-domain of human methionyl-tRNA synthetase has a tRNA-sequestering function
    M Kaminska
    Laboratoire d Enzymologie et Biochimie Structurales, CNRS, 1 Avenue de la Terrasse, 91190 Gif sur Yvette, France
    Biochemistry 40:14309-16. 2001
    ..It may ensure an efficient capture of tRNA(Met) under conditions of suboptimal deacylated tRNA concentration prevailing in vivo, and may instigate direct transfer of aminoacylated tRNA from the synthetase to elongation factor EF-1alpha...
  21. pmc Incorporation of azides into recombinant proteins for chemoselective modification by the Staudinger ligation
    Kristi L Kiick
    Department of Polymer Science and Engineering, University of Massachusetts, Amherst, MA 01003, USA
    Proc Natl Acad Sci U S A 99:19-24. 2002
    ..Incorporation of azide-functionalized amino acids into proteins in vivo provides opportunities for protein modification under native conditions and selective labeling of proteins in the intracellular environment...
  22. ncbi Three-dimensional architecture of the eukaryotic multisynthetase complex determined from negatively stained and cryoelectron micrographs
    Mona T Norcum
    Department of Biochemistry, The University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216, USA
    FEBS Lett 512:298-302. 2002
    ..The structures have openings or indentations on most sides. Maximum dimensions are ca. 19x16x10 nm. The central cavity is 4 nm in diameter and extends two-thirds of the length of the particle...
  23. ncbi Potent and selective inhibitors of bacterial methionyl tRNA synthetase derived from an oxazolone-dipeptide scaffold
    Manish Tandon
    ArQule Inc, 19 Presidential Way, Woburn, MA 01801, USA
    Bioorg Med Chem Lett 14:1909-11. 2004
    ..As a result of the SAR expansion compound 14a was identified, as a potent SaMetRS inhibitor (IC(50)=18 nM) having moderate inhibition of MetRS derived from Enterococci faecalis (IC(50)=3.51 microM)...
  24. ncbi Definition of the heterocyclic pharmacophore of bacterial methionyl tRNA synthetase inhibitors: potent antibacterially active non-quinolone analogues
    Richard L Jarvest
    GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK
    Bioorg Med Chem Lett 14:3937-41. 2004
    ..Compound 46 demonstrated very good antibacterial activity against panels of antibiotic-resistant staphylococci and enterococci...
  25. ncbi Deoxyribosyl analogues of methionyl and isoleucyl sulfamate adenylates as inhibitors of methionyl-tRNA and isoleucyl-tRNA synthetases
    Sung Eun Kim
    Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Kwanak Ku, Seoul 151 742, Republic of Korea
    Bioorg Med Chem Lett 15:3389-93. 2005
    ..coli MRS revealed that the lack of the two hydroxyl groups on ribose was compensated by the formation of an extra hydrogen bond between the ring oxygen and His24, resulting in a small activity reduction...
  26. ncbi Structure and function of the C-terminal domain of methionyl-tRNA synthetase
    Thibaut Crepin
    Laboratoire de Biochimie, Unité Mixte de Recherche 7654, CNRS Ecole Polytechnique, F 91128 Palaiseau cedex, France
    Biochemistry 41:13003-11. 2002
    ..Comparison of the resulting mutants to native and C-truncated MetRS shows that the presence of the appended C-domain improves tRNA(Met) binding affinity. However, dimer formation is required to evidence the gain in affinity...
  27. ncbi Crystallographic study at 2.5 A resolution of the interaction of methionyl-tRNA synthetase from Escherichia coli with ATP
    S Brunie
    Laboratoire de Biochimie CNRS URA 240, Ecole Polytechnique, Palaiseau, France
    J Mol Biol 216:411-24. 1990
    ..The gamma-phosphate group interacts with the carbonyl oxygen atom and the side-chain of Asn17.(ABSTRACT TRUNCATED AT 400 WORDS)..
  28. pmc Horizontal transfer of drug-resistant aminoacyl-transfer-RNA synthetases of anthrax and Gram-positive pathogens
    James R Brown
    Bioinformatics Division, GlaxoSmithKline, 1250 South Collegeville Road, UP1345, Collegeville, Pennsylvania 19426, USA
    EMBO Rep 4:692-8. 2003
    ..This study shows the importance of understanding complex evolutionary networks of ancient horizontal gene transfer for the development of novel antibiotics...
  29. pmc Extension of a local backbone description using a structural alphabet: a new approach to the sequence-structure relationship
    Alexandre G de Brevern
    Equipe de Bioinformatique Genomique et Moleculaire EBGM, INSERM U436, Universite Denis Diderot Paris 7, France
    Protein Sci 11:2871-86. 2002
    ..The results show that the 3D structure of these protein data banks can be easily described by a combination of subgraphs included in the network. Finally, a Bayesian probabilistic approach improved the prediction rate by 4%...
  30. ncbi Methionyl-tRNA synthetase
    M A Deniziak
    Institute of Bioorganic Chemistry of the Polish Academy of Sciences, Poznan
    Acta Biochim Pol 48:337-50. 2001
    ..g. Arg-Gly-Asp (RGD) motifs. Additional activities involve MetRS in the maintenance of translational fidelity and in coordination of ribosome biogenesis with protein synthesis...
  31. ncbi Characterization of MSM1, the structural gene for yeast mitochondrial methionyl-tRNA synthetase
    A Tzagoloff
    Department of Biological Sciences, Columbia University, New York, NY 10027
    Eur J Biochem 179:365-71. 1989
    ..Based on the primary-sequence similarities of the three proteins, the mitochondrial enzyme appears to be more related to the bacterial than to the yeast cytoplasmic methionyl-tRNA synthetase...
  32. ncbi Cloning and characterization of mitochondrial methionyl-tRNA synthetase from a pathogenic fungi Candida albicans
    S W Lee
    Department of Biology, Sung Kyun Kwan University, 300 Chunchundong, Jangangu, Suwon, Kyunggido 440 746, South Korea
    Gene 215:311-8. 1998
    ..This cross-species aminoacylation activity suggests the conservation of interaction mode between tRNAMet and MetRS...
  33. ncbi Transcription and regulation of expression of the Escherichia coli methionyl-tRNA synthetase gene
    F Dardel
    Laboratoire de Biochimie, Ecole Polytechnique, Palaiseau, France
    Mol Gen Genet 223:121-33. 1990
    ..Transcription of a metG::lacZ fusion is induced in a metG mutant and, reciprocally, repression is observed in a methionyl-tRNA synthetase overproducing strain. A model of metG expression control is proposed...
  34. ncbi Methionyl-tRNA synthetase gene from an extreme thermophile, Thermus thermophilus HB8. Molecular cloning, primary-structure analysis, expression in Escherichia coli, and site-directed mutagenesis
    O Nureki
    Department of Biophysics and Biochemistry, Faculty of Science, University of Tokyo, Japan
    J Biol Chem 266:3268-77. 1991
    ..Further upstream a region contains a nucleotide sequence homologous to that of the 5' half of T. thermophilus initiator tRNA(Met)...
  35. ncbi Biochemical and phylogenetic analyses of methionyl-tRNA synthetase isolated from a pathogenic microorganism, Mycobacterium tuberculosis
    S Kim
    Sung Kyun Kwan University, Department of Biology, Suwon, Kyunggido, South Korea
    FEBS Lett 427:259-62. 1998
    ....
  36. ncbi Methionyl-tRNA synthetase from Escherichia coli. Primary structure of the active crystallised tryptic fragment
    D G Barker
    Eur J Biochem 127:449-57. 1982
    ..We have also sequenced 300 nucleotides upstream of this coding segment where we find a large invert repeat in the putative methionyl-tRNA synthetase promoter region...
  37. ncbi Genetic engineering of methionyl-tRNA synthetase: in vitro regeneration of an active synthetase by proteolytic cleavage of a methionyl-tRNA synthetase--beta-galactosidase chimeric protein
    P H Hirel
    Laboratoire de Biochimie, CNRS UA240, Palaiseau, France
    Biochimie 70:773-82. 1988
    ..The methionyl-tRNA synthetase moiety can be regenerated by mild proteolysis, thus providing a simple method for purifying and studying mutated proteins...
  38. ncbi Expression, localization and alternative function of cytoplasmic asparaginyl-tRNA synthetase in Brugia malayi
    Michael Kron
    Department of Medicine, Michigan State University, B323 Life Science Building, East Lansing, MI 48824, USA
    Mol Biochem Parasitol 129:33-9. 2003
    ..These data support the hypothesis that all AARS are not equally expressed in B. malayi and that these enzymes may demonstrate important alternative functions in filaria...
  39. ncbi Structural basis for translational fidelity ensured by transfer RNA lysidine synthetase
    Kotaro Nakanishi
    Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama, Kanagawa 225 8501, Japan
    Nature 461:1144-8. 2009
    ..Our findings also provide a rationale for the necessity of incorporating specific modifications at the precursor level during tRNA biogenesis...
  40. ncbi Metabolism of homocysteine-thiolactone in plants
    Hieronim Jakubowski
    Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey UMDNJ New Jersey Medical School, International Center for Public Health, Newark, New Jersey 07101, USA
    J Biol Chem 278:6765-70. 2003
    ..Thus, Hcy-thiolactone and Hcy bound to protein by an amide (or peptide) linkage (Hcy-N-protein) are significant components of plant Hcy metabolism...
  41. ncbi Intron positions delineate the evolutionary path of a pervasively appended peptide in five human aminoacyl-tRNA synthetases
    Kiyotaka Shiba
    Department of Protein Engineering, Cancer Institute, Japanese Foundation for Cancer Research, 1 37 1, Kami Ikebukuro, Toshima, Tokyo 170 8455, Japan
    J Mol Evol 55:727-33. 2002
    ..In similar fashion, the motif in glycyl-tRNA synthetase spread to the C terminal of methionyl-tRNA synthetase not later than 1000 million years ago...
  42. pmc Methionyl-tRNA synthetase from Caenorhabditis elegans: a specific multidomain organization for convergent functional evolution
    Svitlana Havrylenko
    Laboratoire d Enzymologie et Biochimie Structurales, CNRS, 91190 Gif sur Yvette, France
    Protein Sci 19:2475-84. 2010
    ....
  43. ncbi Mutations in methylenetetrahydrofolate reductase or cystathionine beta-synthase gene, or a high-methionine diet, increase homocysteine thiolactone levels in humans and mice
    Grazyna Chwatko
    Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, International Center for Public Health, 225 Warren St, Newark, NJ 07101 1709, USA
    FASEB J 21:1707-13. 2007
    ..7-fold and 25-fold increases in plasma and urinary Hcy-thiolactone levels, respectively. Thus, we conclude that hyperhomocysteinemia leads to significant increases in the atherogenic metabolite Hcy-thiolactone in humans and mice...
  44. pmc Extent of N-terminal methionine excision from Escherichia coli proteins is governed by the side-chain length of the penultimate amino acid
    P H Hirel
    Laboratoire de Biochimie, Unité Associée 240 Centre National de la Recherche Scientifique, Ecole Polytechnique, Palaiseu, France
    Proc Natl Acad Sci U S A 86:8247-51. 1989
    ..This molecular model accounts for the rate of N-terminal methionine excision in E. coli, as deduced from the analysis of 100 protein N-terminal sequences...
  45. pmc Genetic dissection of protein-protein interactions in multi-tRNA synthetase complex
    S B Rho
    Department of Biological Science, National Creative Research Initiatives Center for ARS Network, Sung Kyun Kwan University, Suwon, Kyunggido 440 746, Korea
    Proc Natl Acad Sci U S A 96:4488-93. 1999
    ..Thus, small peptide appendices seem to link together different synthetases into a complex. In addition, five interacting pairs that had not been detected previously were suggested from the observed peptide-dependent complexes...
  46. ncbi Identification and origin of Nε-homocysteinyl-lysine isopeptide in humans and mice
    Rafał Głowacki
    Department of Environmental Chemistry, Łódź University, 90 236, Łódź, Poland
    Amino Acids 39:1563-9. 2010
    ..We also show that Nε-Hcy-Lys is generated by proteolytic degradation of N-Hcy-protein in mouse liver extracts. Our data indicate that free Nε-Hcy-Lys is an important pathology-related component of Hcy metabolism in humans and mice...
  47. ncbi The specificity of translational control switched with transfer RNA identity rules
    M Graffe
    Institut de Biologie Physico Chimique, Paris, France
    Science 255:994-6. 1992
    ..This identity swap in the leader messenger RNA indicates that tRNA identity rules may be extended to interactions of synthetases with other RNAs...
  48. ncbi Protein homocysteinylation: a new mechanism of atherogenesis?
    Jerzy Bełtowski
    Department of Pathophysiology, Medical University, Lublin, Poland
    Postepy Hig Med Dosw (Online) 59:392-404. 2005
    ..Protein homocysteinylation may contribute to accelerated atherogenesis in individuals with hyperhomocysteinemia...
  49. ncbi Inhibitory effect of REP3123 on toxin and spore formation in Clostridium difficile, and in vivo efficacy in a hamster gastrointestinal infection model
    Urs A Ochsner
    Replidyne, Inc, Louisville, CO 80027, USA
    J Antimicrob Chemother 63:964-71. 2009
    ..This novel agent was investigated for its ability to block the production of toxins and spores, and was tested for efficacy in vivo in a hamster model...
  50. ncbi Protective mechanisms against homocysteine toxicity: the role of bleomycin hydrolase
    Jaroslaw Zimny
    Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey New Jersey Medical School, International Center for Public Health, Newark, New Jersey 07101, USA
    J Biol Chem 281:22485-92. 2006
    ..Our data suggest that BLH protects cells against Hcy toxicity by hydrolyzing intracellular Hcy-thiolactone...
  51. ncbi Homocysteine thiolactone and protein homocysteinylation in human endothelial cells: implications for atherosclerosis
    H Jakubowski
    Department of Microbiology, UMDNJ New Jersey Medical School, Newark, NJ, USA
    Circ Res 87:45-51. 2000
    ..These data support a hypothesis that metabolic conversion of homocysteine to thiolactone and protein homocysteinylation by thiolactone may play a role in homocysteine-induced vascular damage...
  52. ncbi The role of paraoxonase 1 in the detoxification of homocysteine thiolactone
    Hieronim Jakubowski
    Department of Biochemistry and Biotechnology, University of Life Sciences, Poznan, Poland
    Adv Exp Med Biol 660:113-27. 2010
    ..This article outlines Hcy-thiolactone pathobiology and reviews evidence documenting the role of PON1 in minimizing Hcy-thiolactone and N-Hcy-protein accumulation...
  53. ncbi Pathophysiological consequences of homocysteine excess
    Hieronim Jakubowski
    Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, International Center for Public Health, Newark, NJ 07101, USA
    J Nutr 136:1741S-1749S. 2006
    ..Potential utility of Hcy-thiolactone, N-Hcy-protein, or anti-N-Hcy-protein autoantibodies as markers of Hcy excess is discussed...
  54. ncbi Translational incorporation of S-nitrosohomocysteine into protein
    H Jakubowski
    Department of Microbiology and Molecular Genetics, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07103, USA
    J Biol Chem 275:21813-6. 2000
    ..S-Nitrosylation-mediated translational incorporation of Hcy into protein may occur under natural conditions in cells and contribute to Hcy-induced pathogenesis in atherosclerosis...
  55. ncbi The determination of homocysteine-thiolactone in biological samples
    Hieronim Jakubowski
    Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, International Center for Public Health, Newark 07101, USA
    Anal Biochem 308:112-9. 2002
    ..The data support the conclusion that homocysteine-thiolactone is a ubiquitous metabolite whose levels are directly related to homocysteine levels...
  56. pmc Exome sequencing identifies a significant variant in methionyl-tRNA synthetase (MARS) in a family with late-onset CMT2
    Michael Gonzalez
    Dr John T McDonald Foundation Department of Human Genetics, John P Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA
    J Neurol Neurosurg Psychiatry 84:1247-9. 2013
    ..This is supported by strong functional and evolutionary evidence, yet the absence of additional unrelated cases warrant future studies to substantiate this conclusion. ..
  57. pmc Switching from an induced-fit to a lock-and-key mechanism in an aminoacyl-tRNA synthetase with modified specificity
    Emmanuelle Schmitt
    Ecole Polytechnique, Laboratoire de Biochimie, F 91128 Palaiseau cedex, France CNRS, UMR7654, Laboratoire de Biochimie, Ecole Polytechnique, F 91128 Palaiseau cedex, France
    J Mol Biol 394:843-51. 2009
    ..Therefore, the mutations cause the enzyme to switch from an induced-fit mechanism to a lock-and-key one, thereby enhancing its catalytic efficiency...
  58. pmc Crystallization of Mycobacterium smegmatis methionyl-tRNA synthetase in the presence of methionine and adenosine
    Henrik Ingvarsson
    Department of Cell and Molecular Biology, Uppsala University, Biomedical Center, Box 596, SE 751 24 Uppsala, Sweden
    Acta Crystallogr Sect F Struct Biol Cryst Commun 65:618-20. 2009
    ..9, b = 138.9, c = 123.3 A, beta = 124.8 degrees . The presence of three molecules in the asymmetric unit corresponded to a solvent content of 60% and a Matthews coefficient of 3.1 A(3) Da(-1). Structure determination is in progress...
  59. ncbi Determination of three-dimensional structure and residues of the novel tumor suppressor AIMP3/p18 required for the interaction with ATM
    Kyung Jin Kim
    Pohang Accelerator Laboratory, Pohang University of Science and Technology, Pohang 790 784, Korea
    J Biol Chem 283:14032-40. 2008
    ..Thus, this work identified the two potential molecular interaction sites of AIMP3 and determined the residues critical for its tumor-suppressive activity through the interaction with ATM...
  60. ncbi Spectrum of activity and mode of action of REP3123, a new antibiotic to treat Clostridium difficile infections
    Ian A Critchley
    Replidyne, Inc, Louisville, CO 80027, USA
    J Antimicrob Chemother 63:954-63. 2009
    ..The aim of this study was to characterize the antimicrobial profile of REP3123, a novel inhibitor of methionyl-tRNA synthetase (MetRS) in development for the treatment of Clostridium difficile infection...
  61. pmc Structures of Trypanosoma brucei methionyl-tRNA synthetase with urea-based inhibitors provide guidance for drug design against sleeping sickness
    Cho Yeow Koh
    Department of Biochemistry, University of Washington, Seattle, Washington, United States of America
    PLoS Negl Trop Dis 8:e2775. 2014
    ..This suggests a possibility that a general 'ATP-engaging' binding mode can be utilized for the design and development of inhibitors targeting tRNA synthetases of other disease-causing pathogen. ..
  62. ncbi Homocysteine-thiolactone and S-nitroso-homocysteine mediate incorporation of homocysteine into protein in humans
    Hieronim Jakubowski
    Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, International Center for Public Health, Newark 07101 1709, USA
    Clin Chem Lab Med 41:1462-6. 2003
    ..Hcy-thiolactone is present in human plasma. Modification with Hcy-thiolactone leads to protein damage. Hcy-thiolactone is detoxified by Hcy-thiolactonase/paraoxonase present in a subset of high-density lipoprotein particles in humans...
  63. ncbi Variations in clique and community patterns in protein structures during allosteric communication: investigation of dynamically equilibrated structures of methionyl tRNA synthetase complexes
    Amit Ghosh
    Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India 560012
    Biochemistry 47:11398-407. 2008
    ..This ought to enhance our understanding of the functioning of aaRS in general...
  64. ncbi Enzymatic conversion of cytidine to lysidine in anticodon of bacterial isoleucyl-tRNA--an alternative way of RNA editing
    Henri Grosjean
    Laboratoire d Enzymologie et Biochimie Structurales, Centre National de la Recherche Scientifique, 1 Avenue de la Terrasse, F 91198 Gif sur Yvette, France
    Trends Biochem Sci 29:165-8. 2004
  65. ncbi Detection of biological macromolecules on a biochip dedicated to UV specific absorption
    Kristelle Robin
    Thales Research and Technology, Palaiseau Cedex, France
    Biosens Bioelectron 24:1585-91. 2009
    ..This label-free optical method may be helpful in controlling biochip coatings, and subsequent biological coupling at the surface of a biochip...
  66. ncbi The pathophysiological hypothesis of homocysteine thiolactone-mediated vascular disease
    H Jakubowski
    Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, International Center for Public Health, Newark, NJ 07101, USA
    J Physiol Pharmacol 59:155-67. 2008
    ..We conclude that genetic or dietary hyperhomocysteinemia significantly elevates proatherothrombotic metabolites Hcy-thiolactone and N-Hcy-proteins in humans and mice...
  67. pmc Induced resistance to methionyl-tRNA synthetase inhibitors in Trypanosoma brucei is due to overexpression of the target
    Ranae M Ranade
    Department of Medicine, University of Washington, Seattle, Washington, USA
    Antimicrob Agents Chemother 57:3021-8. 2013
    ..This is the first published report of induced drug resistance in the African trypanosome due to overexpression of the target enzyme...
  68. pmc Structure of Leishmania major methionyl-tRNA synthetase in complex with intermediate products methionyladenylate and pyrophosphate
    Eric T Larson
    Department of Biochemistry, University of Washington, Seattle, WA 98195 7742, USA
    Biochimie 93:570-82. 2011
    ....
  69. ncbi Investigation of bioisosteric effects on the interaction of substrates/ inhibitors with the methionyl-tRNA synthetase from Escherichia coli
    M D Vaughan
    Department of Chemistry, University of Waterloo, 200 University Avenue, Waterloo, ON, N2L 3G1, Canada
    Med Chem 1:227-37. 2005
    ..25 nM and 2.4 nM respectively. A discussion of this data in relation to structural information provided by the recent determination of the three-dimensional structures of the E. coli enzyme with several of these compounds is presented...
  70. ncbi Design and synthesis of quinolinones as methionyl-tRNA synthetase inhibitors
    - Farhanullah
    Laboratory of Medicinal Chemistry, Research Institute of Pharmaceutical Sciences, College of Pharmacy, Seoul National University, Shinlim Dong, Seoul 151 742, Republic of Korea
    Bioorg Med Chem 14:7154-9. 2006
    ..aureus, two Enterococcus faecalis, and one Enterococcus faecium. Among all the synthesized quinolinones, compound 20 displayed significant inhibitory activities in the strains of E. faecalis and E. faecium...
  71. pmc Misacylation of specific nonmethionyl tRNAs by a bacterial methionyl-tRNA synthetase
    Thomas E Jones
    Department of Biochemistry and Molecular Biology and Institute of Biophysical Dynamics, University of Chicago, Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 108:6933-8. 2011
    ....
  72. pmc Structural basis of yeast aminoacyl-tRNA synthetase complex formation revealed by crystal structures of two binary sub-complexes
    Hannes Simader
    Structural and Computational Biology Unit, European Molecular Biology Laboratory EMBL, Meyerhofstrasse 1, D 69117 Heidelberg, Germany
    Nucleic Acids Res 34:3968-79. 2006
    ..The results demonstrate a novel role for this fold as a heteromerization domain specific to eukaryotic aaRS, associated proteins and protein translation elongation factors...
  73. pmc Eukaryotic-like Ser/Thr protein kinases SpkC/F/K are involved in phosphorylation of GroES in the Cyanobacterium synechocystis
    Anna Zorina
    Institute of Plant Physiology, Botanicheskaya Street 35, 127276 Moscow, Russia
    DNA Res 18:137-51. 2011
    ..This suggests that these three STPKs are organized in a sequential order or a cascade and they work one after another to finally phosphorylate the GroES...
  74. ncbi In situ kinetic trapping reveals a fingerprint of reversible protein thiol oxidation in the mitochondrial matrix
    Johanna Engelhard
    Division of Redox Regulation, DKFZ ZMBH Alliance, German Cancer Research Center, 69120 Heidelberg, Germany
    Free Radic Biol Med 50:1234-41. 2011
    ..In conclusion, we find that in situ kinetic trapping provides starting points for future functional studies of intramitochondrial redox regulation...
  75. pmc Dual role of methionyl-tRNA synthetase in the regulation of translation and tumor suppressor activity of aminoacyl-tRNA synthetase-interacting multifunctional protein-3
    Nam Hoon Kwon
    Medicinal Bioconvergence Research Center, Seoul National University, Seoul 151 742, Korea
    Proc Natl Acad Sci U S A 108:19635-40. 2011
    ....
  76. ncbi Anti-N-homocysteinylated protein autoantibodies and cardiovascular disease
    Hieronim Jakubowski
    Department of Microbiology and Molecular Genetics, UMDNJ New Jersey Medical School, International Center for Public Health, Newark, NJ 07101 1709, USA
    Clin Chem Lab Med 43:1011-4. 2005
    ....
  77. ncbi Arc1p: anchoring, routing, coordinating
    Mathieu Frechin
    UPR 9002 Architecture et Réactivité de l ARN, Universite de Strasbourg, CNRS, Institut de Biologie Moleculaire et Cellulaire, 15 rue Rene Descartes, F 67084 Strasbourg CEDEX, France
    FEBS Lett 584:427-33. 2010
    ....
  78. ncbi Promiscuous methionyl-tRNA synthetase mediates adaptive mistranslation to protect cells against oxidative stress
    Jin Young Lee
    Medicinal Bioconvergence Research Center, College of Pharmacy, Seoul National University, Seoul 151 742, Korea
    J Cell Sci 127:4234-45. 2014
    ..This controlled inaccuracy of MRS seems to serve as a defense mechanism against ROS-mediated damage at the cost of translational fidelity. ..
  79. ncbi Crystal structure of Escherichia coli methionyl-tRNA synthetase at 2.5 A resolution
    C Zelwer
    J Mol Biol 155:63-81. 1982
  80. pmc Regulation of methionyl-transfer ribonucleic acid synthetase formation in Escherichia coli and Salmonella typhimurium
    E R Archibold
    J Bacteriol 114:1007-13. 1973
    ..These results suggest that aminoacylation of methionine-tRNA is a necessary step in repression control of methionyl-tRNA synthetase of both E. coli and S. typhimurium strains...
  81. ncbi Identification of an expanded set of translationally active methionine analogues in Escherichia coli
    K L Kiick
    Department of Polymer Science and Engineering, University of Massachusetts, Amherst, MA 01003, USA
    FEBS Lett 502:25-30. 2001
    ..These investigations suggest important opportunities for protein engineering, as expansion of the translational apparatus toward other amino acid analogues by similar strategies should also be possible...
  82. ncbi Importance of the anticodon sequence in the aminoacylation of tRNAs by methionyl-tRNA synthetase and by valyl-tRNA synthetase in an Archaebacterium
    V Ramesh
    Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    J Biol Chem 276:3660-5. 2001
    ..The CAU-->GAC anticodon mutant is most likely aminoacylated with valine in vivo. Thus, the anticodon plays an important role in the recognition of tRNA by at least two of the halobacterial aminoacyl-tRNA synthetases...
  83. ncbi Modification of aminoacyl-tRNA synthetases with pyridoxal-5'-phosphate. Identification of the labeled amino acid residues
    T Kalogerakos
    Laboratoire de Biochemie, CNRS URA 240, Ecole Polytechnique, Palaiseau, France
    Biochimie 76:33-44. 1994
    ..It is concluded that these residues participate to the binding sites of the phosphates of ATP on the studied synthetases...
  84. pmc L-arginine recognition by yeast arginyl-tRNA synthetase
    J Cavarelli
    UPR 9004 Biologie Structurale, , CNRS INSERM ULP, BP 163, 67404 Illkirch Cedex, France
    EMBO J 17:5438-48. 1998
    ..This tyrosine is also conserved in other class I aaRS active sites but plays several functional roles. The ArgRS structure allows the definition of a new framework for sequence alignments and subclass definition in class I aaRSs...
  85. pmc Molecular mimicry in translational control of E. coli threonyl-tRNA synthetase gene. Competitive inhibition in tRNA aminoacylation and operator-repressor recognition switch using tRNA identity rules
    P Romby
    UPR du CNRS no 9002, Institut de Biologie Moleculaire et Cellulaire, Strasbourg, France
    Nucleic Acids Res 20:5633-40. 1992
    ..The present data demonstrate that the anticodon-like sequence is one major determinant for the identity of the operator and the regulation specificity. It further shows that the tRNA-like operator obeys to tRNA identity rules...
  86. ncbi The p43 component of the mammalian multi-synthetase complex is likely to be the precursor of the endothelial monocyte-activating polypeptide II cytokine
    S Quevillon
    Laboratoire d Enzymologie et Biochimie Structurales, CNRS UPR 9063, 91190 Gif sur Yvette, France
    J Biol Chem 272:32573-9. 1997
    ..The release of a truncated p43 from the complex could be involved in mediation of the signaling of tumor cells and stimulation of an acute inflammatory response...
  87. ncbi Further study on association of 5SrRNA-L5 protein complex and methionyl-tRNA to methionyl-tRNA synthetase in the macromolecular aminoacyl-tRNA synthetase complex
    K Ogata
    Institute for Gene Expression, Dobashi Kyoritsu Hospital, Ehime
    J Biochem 120:869-80. 1996
    ..5SRNP and 5SrRNA markedly enhanced the MetRS activity in the MetRS complex, indicating that 5SRNP(A) plays a role as a positive effector of MetRS...
  88. ncbi Human tyrosyl-tRNA synthetase shares amino acid sequence homology with a putative cytokine
    T A Kleeman
    Department of Biochemistry and Molecular Biology, Louisiana State University Medical Center, Shreveport, Louisiana 71130 3932, USA
    J Biol Chem 272:14420-5. 1997
    ....
  89. ncbi Mapping of the zinc binding domain of Escherichia coli methionyl-tRNA synthetase
    D Fourmy
    Unité de Recherche Associée 240 du Centre National de la Recherche Scientifique Ecole Polytechnique, Palaiseau, France
    J Mol Biol 231:1068-77. 1993
    ..The possible role of the zinc atom and of its chelating residues in the folding of the active centre of methionyl-tRNA synthetase is discussed...
  90. ncbi Molecular recognition governing the initiation of translation in Escherichia coli. A review
    E Schmitt
    Laboratoire de Biochimie, URA CNRS no 1970, Ecole Polytechnique, Palaiseau, France
    Biochimie 78:543-54. 1996
    ..Finally, peptide deformylase and methionine aminopeptidase, which catalyze the amino terminal maturation of nascent polypeptides, can also be associated to the translation initiation process...
  91. ncbi Structure and expression of two aminoacyl-tRNA synthetase genes from Saccharomyces cerevisiae
    F Meussdoerffer
    J Biol Chem 258:6293-9. 1983
    ..Two polyadenylated transcripts are homologous to the methionyl-tRNA synthetase gene. The major MES1 transcript is not affected by the general control or starvation for several different amino acids, including methionine...
  92. ncbi Contributions of aminoacyl-tRNA synthetase-interacting multifunctional protein-3 to mammalian translation initiation
    Min Jeong Ku
    Department of Life Science, Gachon University, San 65, Bokjeong dong, Sujeong Gu, Seongnam si, 461 701, Kyeonggi Do, Korea
    Amino Acids 44:1241-5. 2013
    ..Due to the protections that MRS and eIF2γ are provided from the interactions with AIMP3, cellular levels of MRS and eIF2γ may be able to be maintained high enough for their canonical and/or non-canonical functions...
  93. pmc Discovery of aminoacyl-tRNA synthetase activity through cell-surface display of noncanonical amino acids
    A James Link
    Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA
    Proc Natl Acad Sci U S A 103:10180-5. 2006
    ..The Leu-13 --> Gly (L13G) mutation is found in each of the three MetRS mutants, and the MetRS variant containing this single mutation is highly efficient in producing recombinant proteins that contain azidonorleucine...
  94. ncbi Convergent evolution of two different random RNAs for specific interaction with methionyl-tRNA synthetase
    Taehee Kang
    Center for Medicinal Protein Network and Systems Biology, Seoul National University, Seoul 151 742, Republic of Korea
    Biochem Biophys Res Commun 432:281-6. 2013
    ....
  95. ncbi Leucyl-tRNA synthetase from the hyperthermophilic bacterium Aquifex aeolicus recognizes minihelices
    Min Gang Xu
    State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, The Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China
    J Biol Chem 279:32151-8. 2004
    ..Therefore, the context of tRNA is crucial for the editing of mischarged products. However, the minihelix(Leu) cannot be misaminoacylated, perhaps because of the tRNA-independent pretransfer editing activity of alpha beta-LeuRS...
  96. pmc Adaptation to tRNA acceptor stem structure by flexible adjustment in the catalytic domain of class I tRNA synthetases
    Cuiping Liu
    Department of Biochemistry and Molecular Biology, Thomas Jefferson University, Philadelphia, PA 19107, USA
    RNA 18:213-21. 2012
    ..This work demonstrates that by flexible insertion of a structural motif to dock on 1-72, the catalytic domain of class I tRNA synthetases can acquire structural plasticity to adapt to changes at the end of the tRNA acceptor stem...
  97. pmc Large mutational target size for rapid emergence of bacterial persistence
    Hany S Girgis
    Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA
    Proc Natl Acad Sci U S A 109:12740-5. 2012
    ..Our findings reveal a large mutational target size for increasing persistence frequency, which has fundamental implications for the emergence of antibiotic tolerance in the clinical setting...
  98. pmc Mutations in the mitochondrial methionyl-tRNA synthetase cause a neurodegenerative phenotype in flies and a recessive ataxia (ARSAL) in humans
    Vafa Bayat
    Program in Developmental Biology, Baylor College of Medicine, Houston, Texas, United States of America
    PLoS Biol 10:e1001288. 2012
    ..Patient cells also exhibited reduced Complex I activity, increased ROS, and a slower cell proliferation rate, similar to Drosophila Aats-met mutants...
  99. pmc Role of methionine and formylation of initiator tRNA in initiation of protein synthesis in Escherichia coli
    U Varshney
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139
    J Bacteriol 174:7819-26. 1992
    ..Consequently, a subset of mutant tRNAs which are defective in formylation and therefore inactive in initiation when they are aminoacylated with glutamine become partially active when MetRS is overproduced...
  100. ncbi Identification of the metal ligands and characterization of a putative zinc finger in methionyl-tRNA synthetase
    B Xu
    Department of Biochemistry and Molecular Biology, University of Texas Medical School, Houston 77225
    J Biol Chem 268:16259-64. 1993
    ..coli methionyl-tRNA synthetase. The role of the enzyme-bound metal appears to be structural and not directly involved in catalysis...
  101. pmc Metal-binding site in a class I tRNA synthetase localized to a cysteine cluster inserted into nucleotide-binding fold
    J A Landro
    Department of Biology, Massachusetts Institute of Technology, Cambridge 02139
    Proc Natl Acad Sci U S A 90:2261-5. 1993
    ..With this result there is now at least one example of a class I and of a class II E. coli tRNA synthetase with a metal-binding domain important for activity inserted into the catalytic domain...

Research Grants4

  1. Structure-based Optimization of T. brucei methionyl tRNA Synthetase Inhibitors
    Erkang Fan; Fiscal Year: 2013
    ..The goal for this project is to identify one lead and one backup compound that are ready for comprehensive GLP preclinical pharmacology and toxicology studies for further development. ..
  2. A novel approach to characterize the Toxoplasma gondii secretome in vivo
    Jon P Boyle; Fiscal Year: 2013
    ..Such effectors may represent new potential targets for therapeutic intervention. ..
  3. PROTEIN-NUCLEIC ACID INTERACTIONS
    Umadas Maitra; Fiscal Year: 1992
    ....
  4. Mechanisms of Disease in the Newborn Human Infant
    F Cole; Fiscal Year: 2006
    ..As such, this program should provide for new pediatric scholars to lead the way for future advances in this important area of child health. ..