multienzyme complexes

Summary

Summary: Systems of enzymes which function sequentially by catalyzing consecutive reactions linked by common metabolic intermediates. They may involve simply a transfer of water molecules or hydrogen atoms and may be associated with large supramolecular structures such as MITOCHONDRIA or RIBOSOMES.

Top Publications

  1. ncbi Bisphosphonate inhibitors of Toxoplasma gondi growth: in vitro, QSAR, and in vivo investigations
    Yan Ling
    Laboratory of Molecular Parasitology, Department of Pathobiology and Center for Zoonoses Research, University of Illinois at Urbana Champaign, 2001 South Lincoln Avenue, Urbana, Illinois, 61802, USA
    J Med Chem 48:3130-40. 2005
  2. ncbi Identification and functional analysis of RNase E of Vibrio angustum S14 and two-hybrid analysis of its interaction partners
    Melissa A Erce
    Systems Biology Laboratory, School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
    Biochim Biophys Acta 1794:1107-14. 2009
  3. pmc Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade
    Simon A Hawley
    Division of Molecular Physiology, University of Dundee, Dundee DD1 5EH, UK
    J Biol 2:28. 2003
  4. pmc Virulence of Mycobacterium tuberculosis depends on lipoamide dehydrogenase, a member of three multienzyme complexes
    Aditya Venugopal
    Department of Microbiology and Immunology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA
    Cell Host Microbe 9:21-31. 2011
  5. ncbi Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase
    Simon A Hawley
    Division of Molecular Physiology University of Dundee, Dundee, Scotland, United Kingdom
    Cell Metab 2:9-19. 2005
  6. ncbi LKB1 is the upstream kinase in the AMP-activated protein kinase cascade
    Angela Woods
    Cellular Stress Group, MRC Clinical Sciences Centre, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom
    Curr Biol 13:2004-8. 2003
  7. ncbi Characterization of the AMP-activated protein kinase kinase from rat liver and identification of threonine 172 as the major site at which it phosphorylates AMP-activated protein kinase
    S A Hawley
    Biochemistry Department, The University, Dundee DD1 4HN, Scotland, United Kingdom
    J Biol Chem 271:27879-87. 1996
  8. ncbi Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells
    Angela Woods
    Cellular Stress Group, MRC Clinical Sciences Centre, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom
    Cell Metab 2:21-33. 2005
  9. ncbi Structure and functions of the 20S and 26S proteasomes
    O Coux
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Annu Rev Biochem 65:801-47. 1996
  10. ncbi The RNA degradosome of Escherichia coli: an mRNA-degrading machine assembled on RNase E
    Agamemnon J Carpousis
    Laboratoire de Microbiologie et Genetique Moleculaires, Unité Mixte de Recherche 5100, Centre National de la Recherche Scientifique et Université Paul Sabatier, 31062 Toulouse, France
    Annu Rev Microbiol 61:71-87. 2007

Detail Information

Publications282 found, 100 shown here

  1. ncbi Bisphosphonate inhibitors of Toxoplasma gondi growth: in vitro, QSAR, and in vivo investigations
    Yan Ling
    Laboratory of Molecular Parasitology, Department of Pathobiology and Center for Zoonoses Research, University of Illinois at Urbana Champaign, 2001 South Lincoln Avenue, Urbana, Illinois, 61802, USA
    J Med Chem 48:3130-40. 2005
    ..Overall, these results indicate that alkyl bisphosphonates are promising compounds for further development as agents against Toxoplasma gondii growth, in vivo...
  2. ncbi Identification and functional analysis of RNase E of Vibrio angustum S14 and two-hybrid analysis of its interaction partners
    Melissa A Erce
    Systems Biology Laboratory, School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, NSW, Australia
    Biochim Biophys Acta 1794:1107-14. 2009
    ..The role of RNase E as a hub protein and the implications of microdomain-mediated interactions in relation to specificity and function are discussed...
  3. pmc Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade
    Simon A Hawley
    Division of Molecular Physiology, University of Dundee, Dundee DD1 5EH, UK
    J Biol 2:28. 2003
    ..We recently showed that LKB1 exists as a complex with two accessory subunits, STRAD alpha/beta and MO25 alpha/beta...
  4. pmc Virulence of Mycobacterium tuberculosis depends on lipoamide dehydrogenase, a member of three multienzyme complexes
    Aditya Venugopal
    Department of Microbiology and Immunology, Weill Cornell Medical College, 1300 York Avenue, New York, NY 10065, USA
    Cell Host Microbe 9:21-31. 2011
    ..Mtb deficient in both DlaT and PdhC phenocopies Lpd-deficient Mtb. Thus, Mtb critically requires BCKADH along with PDH and PNR/P for pathogenesis. These findings position Lpd as a potential target for anti-infectives against Mtb...
  5. ncbi Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase
    Simon A Hawley
    Division of Molecular Physiology University of Dundee, Dundee, Scotland, United Kingdom
    Cell Metab 2:9-19. 2005
    ..Our results suggest a potential Ca(2+)-dependent neuroprotective pathway involving phosphorylation and activation of AMPK by CaMKKbeta...
  6. ncbi LKB1 is the upstream kinase in the AMP-activated protein kinase cascade
    Angela Woods
    Cellular Stress Group, MRC Clinical Sciences Centre, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom
    Curr Biol 13:2004-8. 2003
    ..These results identify a link between two protein kinases, previously thought to lie in unrelated, distinct pathways, that are associated with human diseases...
  7. ncbi Characterization of the AMP-activated protein kinase kinase from rat liver and identification of threonine 172 as the major site at which it phosphorylates AMP-activated protein kinase
    S A Hawley
    Biochemistry Department, The University, Dundee DD1 4HN, Scotland, United Kingdom
    J Biol Chem 271:27879-87. 1996
    ..A., Selbert, M. A., Goldstein, E. G., Edelman, A. M., Carling, D., and Hardie, D. G. (1995) J. Biol. Chem. 270, 27186-27191)...
  8. ncbi Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells
    Angela Woods
    Cellular Stress Group, MRC Clinical Sciences Centre, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, United Kingdom
    Cell Metab 2:21-33. 2005
    ..These results demonstrate that AMPK is regulated by at least two upstream kinases and suggest that AMPK may play a role in Ca(2+)-mediated signal transduction pathways...
  9. ncbi Structure and functions of the 20S and 26S proteasomes
    O Coux
    Department of Cell Biology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Annu Rev Biochem 65:801-47. 1996
    ..This article focuses on recent progress concerning the biochemical mechanisms and intracellular functions of the 20S and 26S proteasomes...
  10. ncbi The RNA degradosome of Escherichia coli: an mRNA-degrading machine assembled on RNase E
    Agamemnon J Carpousis
    Laboratoire de Microbiologie et Genetique Moleculaires, Unité Mixte de Recherche 5100, Centre National de la Recherche Scientifique et Université Paul Sabatier, 31062 Toulouse, France
    Annu Rev Microbiol 61:71-87. 2007
    ....
  11. pmc Stoichiometry and architecture of active DNA replication machinery in Escherichia coli
    Rodrigo Reyes-Lamothe
    Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK
    Science 328:498-501. 2010
    ..Single-strand binding protein has a broader spatial distribution than the core components, with 5 to 11 tetramers per replisome. This in vivo technique could provide single-molecule insight into other molecular machines...
  12. ncbi The Anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways
    Lee G D Fryer
    Cellular Stress Group, Medical Research Council Clinical Sciences Centre, Hammersmith Hospital, DuCane Road, London W12 0NN, United Kingdom
    J Biol Chem 277:25226-32. 2002
    ..Our results demonstrate that AMPK can be activated by at least two distinct signaling mechanisms and suggest that it may play a wider role in the cellular stress response than was previously understood...
  13. pmc Single-molecule studies reveal the function of a third polymerase in the replisome
    Roxana E Georgescu
    The Rockefeller University, Howard Hughes Medical Institute, New York, New York, USA
    Nat Struct Mol Biol 19:113-6. 2012
    ..Second, tripolymerase replisomes are much more processive than dipolymerase replisomes. These features account for the unexpected three-polymerase-structure of bacterial replisomes...
  14. ncbi The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism
    Simon A Hawley
    Division of Molecular Physiology, School of Life Sciences and Wellcome Trust Biocentre, Dundee University, Dundee, Scotland, UK
    Diabetes 51:2420-5. 2002
    ..Our results also show that AMPK can be activated by mechanisms other than changes in the cellular AMP-to-ATP ratio...
  15. ncbi 5-Aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside inhibits cancer cell proliferation in vitro and in vivo via AMP-activated protein kinase
    Ramandeep Rattan
    Department of Pediatrics, Medical University of South Carolina, Charleston, South Carolina 29425, USA
    J Biol Chem 280:39582-93. 2005
    ..Altogether, these results indicate that AICAR can be utilized as a therapeutic drug to inhibit cancer, and AMPK can be a potential target for treatment of various cancers independent of the functional tumor suppressor gene, LKB...
  16. pmc RNase E-based ribonucleoprotein complexes: mechanical basis of mRNA destabilization mediated by bacterial noncoding RNAs
    Teppei Morita
    Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa, Nagoya 464 8602, Japan
    Genes Dev 19:2176-86. 2005
    ..The formation of ribonucleoprotein complexes containing RNases could be a general way by which small RNAs destabilize target mRNAs in both prokaryotes and eukaryotes...
  17. ncbi The ubiquitin-proteasome pathway is required for processing the NF-kappa B1 precursor protein and the activation of NF-kappa B
    V J Palombella
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, Massachusetts 02138
    Cell 78:773-85. 1994
    ..Thus, the ubiquitin-proteasome pathway functions not only in the complete degradation of polypeptides, but also in the regulated processing of precursors into active proteins...
  18. ncbi Ubiquitin-dependent protein degradation
    M Hochstrasser
    Department of Biochemistry and Molecular Biology, University of Chicago, Illinois 60637, USA
    Annu Rev Genet 30:405-39. 1996
    ..This diversity underlies both the high substrate specificity of the ubiquitin system and the variety of regulatory mechanisms that it serves...
  19. ncbi A gated channel into the proteasome core particle
    M Groll
    Max Planck Institut fur Biochemie, D 82152 Martinsried, Germany
    Nat Struct Biol 7:1062-7. 2000
    ..Inhibition by the alpha-subunit tails is relieved upon binding of the regulatory particle to the CP to form the proteasome holoenzyme...
  20. pmc Autotaxin, a secreted lysophospholipase D, is essential for blood vessel formation during development
    Laurens A van Meeteren
    Division of Cellular Biochemistry, The Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands
    Mol Cell Biol 26:5015-22. 2006
    ....
  21. ncbi A DEAD-box RNA helicase in the Escherichia coli RNA degradosome
    B Py
    Nuffield Department of Clinical Biochemisstry and Imperial Cancer Research Fund Laboratories, Institute of Molecular Medicine, UK
    Nature 381:169-72. 1996
    ..These results suggest that RhlB acts by unwinding RNA structures that impede the processive activity of PNPase. RhlB is thus an important enzyme in mRNA turnover...
  22. pmc beta-catenin is a target for the ubiquitin-proteasome pathway
    H Aberle
    Max Planck Institute for Immunobiology, Department of Molecular Embryology, Freiburg, Germany
    EMBO J 16:3797-804. 1997
    ..We show that ubiquitination of beta-catenin is greatly reduced in Wnt-expressing cells, providing the first evidence that the ubiquitin-proteasome degradation pathway may act downstream of GSK3beta in the regulation of beta-catenin...
  23. ncbi MHC class I expression in mice lacking the proteasome subunit LMP-7
    H J Fehling
    Basel Institute for Immunology, Switzerland
    Science 265:1234-7. 1994
    ..This demonstrates the involvement of LMP-7 in the MHC class I presentation pathway and suggests that LMP-7 functions as an integral part of the peptide supply machinery...
  24. ncbi Enolase in the RNA degradosome plays a crucial role in the rapid decay of glucose transporter mRNA in the response to phosphosugar stress in Escherichia coli
    Teppei Morita
    Division of Biological Science, Graduate School of Science, Nagoya University, Chikusa, Nagoya 464 8602, Japan
    Mol Microbiol 54:1063-75. 2004
    ..In addition, we show that PNPase and RhlB within the degradosome cooperate to eliminate short degradation intermediates of ptsG mRNA...
  25. pmc The chromosomal arsenic resistance genes of Thiobacillus ferrooxidans have an unusual arrangement and confer increased arsenic and antimony resistance to Escherichia coli
    B G Butcher
    Department of Microbiology, University of Stellenbosch, Matieland, South Africa 7602
    Appl Environ Microbiol 66:1826-33. 2000
    ..This divergent orientation was conserved in the four T. ferrooxidans strains investigated...
  26. ncbi Physical and functional interactions among RNase E, polynucleotide phosphorylase and the cold-shock protein, CsdA: evidence for a 'cold shock degradosome'
    Annie Prud'homme-Généreux
    Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, BC, V6T 1Z3, Canada
    Mol Microbiol 54:1409-21. 2004
    ..These findings show that the RNA degradosome is a flexible macromolecular machine capable of adapting to altered environmental conditions...
  27. ncbi Impairment of the ubiquitin-proteasome system by protein aggregation
    N F Bence
    Department of Biological Sciences, Stanford University, Stanford, CA 94305-5020, USA
    Science 292:1552-5. 2001
    ....
  28. ncbi A role for AMP-activated protein kinase in contraction- and hypoxia-regulated glucose transport in skeletal muscle
    J Mu
    Howard Hughes Medical Institute, The Cox Institute, The Department of Medicine, University of Pennsylvania Medical School, Philadelphia, PA 19104, USA
    Mol Cell 7:1085-94. 2001
    ..These data indicate that AMPK transmits a portion of the signal by which muscle contraction increases glucose uptake, but other AMPK-independent pathways also contribute to the response...
  29. ncbi Regulation and biological activities of the autotaxin-LPA axis
    Laurens A van Meeteren
    Division of Cellular Biochemistry, Centre for Biomedical Genetics, The Netherlands Cancer Institute, Plesmanlaan 121, Amsterdam, The Netherlands
    Prog Lipid Res 46:145-60. 2007
    ....
  30. ncbi TSC2 mediates cellular energy response to control cell growth and survival
    Ken Inoki
    Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA
    Cell 115:577-90. 2003
    ..These observations demonstrate a model where TSC2 functions as a key player in regulation of the common mTOR pathway of protein synthesis, cell growth, and viability in response to cellular energy levels...
  31. pmc Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production
    Makiko Umezu-Goto
    Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7 3 1 Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    J Cell Biol 158:227-33. 2002
    ..It also provides potential novel targets for therapy of pathophysiological states including cancer...
  32. pmc Role of AMP-activated protein kinase in mechanism of metformin action
    G Zhou
    Department of Molecular Endocrinology, Merck Research Laboratories, Rahway, New Jersey 07065, USA
    J Clin Invest 108:1167-74. 2001
    ..Activation of AMPK provides a unified explanation for the pleiotropic beneficial effects of this drug; these results also suggest that alternative means of modulating AMPK should be useful for the treatment of metabolic disorders...
  33. ncbi Identification of human plasma lysophospholipase D, a lysophosphatidic acid-producing enzyme, as autotaxin, a multifunctional phosphodiesterase
    Akira Tokumura
    Faculty of Pharmaceutical Sciences, The University of Tokushima, Tokushima 770 8505, Japan
    J Biol Chem 277:39436-42. 2002
    ....
  34. pmc Evolutionarily conserved proteins MnmE and GidA catalyze the formation of two methyluridine derivatives at tRNA wobble positions
    Ismaïl Moukadiri
    Laboratorio de Genetica Molecular, Centro de Investigacion Principe Felipe, 46012 Valencia, Spain
    Nucleic Acids Res 37:7177-93. 2009
    ..Our results allow us to reformulate the bacterial MnmE*GidA dependent pathway and propose a novel mechanism for the modification reactions performed by the MnmE and GidA family proteins...
  35. ncbi Cell cycle regulation via p53 phosphorylation by a 5'-AMP activated protein kinase activator, 5-aminoimidazole- 4-carboxamide-1-beta-D-ribofuranoside, in a human hepatocellular carcinoma cell line
    K Imamura
    Investigative Treatment Division, National Cancer Center Research Institute East, Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan
    Biochem Biophys Res Commun 287:562-7. 2001
    ..Our results suggest that AICAR may regulate cell growth via p53 phosphorylation, and also indicate the possibility of p53 phosphorylation...
  36. ncbi A possible linkage between AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling pathway
    Naoki Kimura
    Biosignal Research Center, Kobe University, Kobe 657 8501, Japan
    Genes Cells 8:65-79. 2003
    ..AMP-activated protein kinase (AMPK) modulates metabolism in response to energy demand by responding to changes in AMP...
  37. pmc Ribonuclease E organizes the protein interactions in the Escherichia coli RNA degradosome
    N F Vanzo
    Laboratoire de Microbiologie et Genetique Moleculaire, UPR 9007, Centre National de la Recherche Scientifique CNRS, 31062 Toulouse Cedex, France
    Genes Dev 12:2770-81. 1998
    ....
  38. ncbi AMP-activated protein kinase activators can inhibit the growth of prostate cancer cells by multiple mechanisms
    Xiaoqin Xiang
    Diabetes Research Unit, Section of Endocrinology, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA
    Biochem Biophys Res Commun 321:161-7. 2004
    ..The results suggest that AMPK is a potential target for the treatment of prostate cancer...
  39. ncbi Microbial arsenic: from geocycles to genes and enzymes
    Rita Mukhopadhyay
    Department of Biochemistry and Molecular Biology, Wayne State University School of Medicine, Detroit, MI 48201, USA
    FEMS Microbiol Rev 26:311-25. 2002
    ..Proposed reaction mechanisms in each case involve three cysteine thiols and S-As bond intermediates, so convergent evolution to similar mechanisms has taken place...
  40. pmc Single-molecule analysis reveals that the lagging strand increases replisome processivity but slows replication fork progression
    Nina Y Yao
    Howard Hughes Medical Institute, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
    Proc Natl Acad Sci U S A 106:13236-41. 2009
    ..The lagging strand significantly increases the processivity of the replisome, possibly reflecting the increased grip to DNA provided by 2 DNA polymerases anchored to sliding clamps on both the leading and lagging strands...
  41. ncbi ER degradation of a misfolded luminal protein by the cytosolic ubiquitin-proteasome pathway
    M M Hiller
    Institut für Biochemie der Universität Stuttgart, Pfaffenwaldring 55, D 70569 Stuttgart, Germany
    Science 273:1725-8. 1996
    ..It is likely that CPY* entered the ER, was glycosylated, and was then transported back out of the ER lumen to the cytoplasmic side of the organelle, where it was conjugated with ubiquitin and degraded...
  42. ncbi Sec61-mediated transfer of a membrane protein from the endoplasmic reticulum to the proteasome for destruction
    E J Wiertz
    Center for Cancer Research, Department of Biology, Massachusetts Institute of Technology, Cambridge 02139, USA
    Nature 384:432-8. 1996
    ..This process involves the Sec61 complex, in what appears to be a reversal of the reaction by which it translocates nascent chains into the endoplasmic reticulum...
  43. ncbi Protein quality control: U-box-containing E3 ubiquitin ligases join the fold
    Douglas M Cyr
    Dept of Cell and Developmental Biology and The UNC Cystic Fibrosis Center, 524 Taylor Hall, University of North Carolina, Chapel Hill, NC 27599 7060, USA
    Trends Biochem Sci 27:368-75. 2002
    ..These data indicate a model for protein quality control in which the interaction of Hsp70 and Hsp90 with co-chaperones that have either folding or degradatory activity helps to determine the fate of non-native cellular proteins...
  44. ncbi The ubiquitin/26S proteasome pathway, the complex last chapter in the life of many plant proteins
    Richard D Vierstra
    Cellular and Molecular Biology Program, Department of Horticulture, 1575 Linden Drive, University of Wisconsin Madison, Madison, WI 53706, USA
    Trends Plant Sci 8:135-42. 2003
    ..Consequently, it appears that the ubiquitin/26S proteasome pathway rivals transcription complexes and protein kinase cascades as the main player in plant cell regulation...
  45. ncbi Structure of 20S proteasome from yeast at 2.4 A resolution
    M Groll
    Max Planck Institut fur Biochemie, Martinsreid, Germany
    Nature 386:463-71. 1997
    ....
  46. pmc An RNA degradosome assembly in Caulobacter crescentus
    Steven W Hardwick
    Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK
    Nucleic Acids Res 39:1449-59. 2011
    ..Finally, we observe that the abundance of RNase E varies through the cell cycle, with maxima at morphological differentiation and cell division. This variation may contribute to the program of gene expression during cell division...
  47. ncbi Inactivating PAPSS2 mutations in a patient with premature pubarche
    Cees Noordam
    Department of Pediatrics Metabolic and Endocrine Disorders, Radboud University Nijmegen Medical Center, Nijmegen, The Netherlands
    N Engl J Med 360:2310-8. 2009
    ..In vitro coincubation of human SULT2A1 and wild-type or mutant PAPSS2 proteins confirmed the inactivating nature of the mutations. These observations indicate that PAPSS2 deficiency is a monogenic adrenocortical cause of androgen excess...
  48. ncbi AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism
    Barbara B Kahn
    Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center and Department of Medicine, Harvard Medical School, Boston, Massachusetts 02215, USA
    Cell Metab 1:15-25. 2005
    ..Through signaling, metabolic, and gene expression effects, AMPK enhances insulin sensitivity and fosters a metabolic milieu that may reduce the risk for obesity and type 2 diabetes...
  49. pmc Coordinating DNA replication by means of priming loop and differential synthesis rate
    Manjula Pandey
    Department of Biochemistry, University of Medicine and Dentistry of New Jersey Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA
    Nature 462:940-3. 2009
    ....
  50. ncbi AMP-activated protein kinase is involved in endothelial NO synthase activation in response to shear stress
    Yingjia Zhang
    Division of Biomedical Sciences, University of California, Riverside, CA 92521 0121, USA
    Arterioscler Thromb Vasc Biol 26:1281-7. 2006
    ..In this study, we investigate the regulation of the AMPK-eNOS pathway in vascular endothelial cells (ECs) by shear stress and the activation of aortic AMPK in a mouse model with a high level of voluntary running (High-Runner)...
  51. pmc A minimal bacterial RNase J-based degradosome is associated with translating ribosomes
    Yulia Redko
    Departement de Microbiologie, Unité Pathogenèse de Helicobacter, Institut Pasteur, 75724 Paris Cedex 15, France
    Nucleic Acids Res 41:288-301. 2013
    ..Together, our findings imply that in H. pylori, the mRNA-degrading machinery is associated with the translation apparatus, a situation till now thought to be restricted to eukaryotes and archaea...
  52. pmc HRD4/NPL4 is required for the proteasomal processing of ubiquitinated ER proteins
    N W Bays
    Division of Biology, Section of Cell and Developmental Biology, University of California San Diego, La Jolla, CA 92093 0347, USA
    Mol Biol Cell 12:4114-28. 2001
    ..We also found that each member of the Cdc48p-Ufd1p-Npl4p complex is individually required for ERAD...
  53. ncbi Sequence-structure-function analysis of the bifunctional enzyme MnmC that catalyses the last two steps in the biosynthesis of hypermodified nucleoside mnm5s2U in tRNA
    Martine Roovers
    Institut de Recherches Microbiologiques Jean Marie Wiame, B 1070 Bruxelles, Belgium
    Proteins 71:2076-85. 2008
    ..Interestingly, the N-terminal domain is capable of independent folding, while the isolated C-terminal domain is incapable of folding on its own, a situation similar to the one reported recently for the rRNA modification enzyme RsmC...
  54. pmc Structural consequences of effector protein complex formation in a diiron hydroxylase
    Lucas J Bailey
    Department of Biochemistry, University of Wisconsin, 433 Babcock Drive, Madison, WI 53706 1544, USA
    Proc Natl Acad Sci U S A 105:19194-8. 2008
    ..This description provides insight into the functional role of effector protein binding in all carboxylate-bridged diiron hydroxylases...
  55. pmc Assay of both activities of the bifunctional tRNA-modifying enzyme MnmC reveals a kinetic basis for selective full modification of cmnm5s2U to mnm5s2U
    David Pearson
    Center for Integrated Protein Science CiPSM at the Department of Chemistry, LMU Munich, Butenandtstrasse 5 13, 81377 Munich, Germany
    Nucleic Acids Res 39:4818-26. 2011
    ..The assay method developed here represents a general approach for the comparative analysis of tRNA-modifying enzymes...
  56. ncbi Mechanisms of MHC class I--restricted antigen processing
    E Pamer
    Department of Internal Medicine and Section of Immunobiology, Yale University School of Medicine, Howard Hughes Medical Institute, New Haven, CT 06510, USA
    Annu Rev Immunol 16:323-58. 1998
    ..A homologous set of beta 2 m-associated membrane glycoproteins, the CD1 molecules, appears to bind lipid-based ligands within the endocytic pathway...
  57. ncbi Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells
    Noriyuki Ouchi
    Molecular Cardiology Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, Massachusetts 02118, USA
    J Biol Chem 279:1304-9. 2004
    ..These data indicate that adiponectin can function to stimulate the new blood vessel growth by promoting cross-talk between AMP-activated protein kinase and Akt signaling within endothelial cells...
  58. ncbi Lysophosphatidic acid and autotaxin stimulate cell motility of neoplastic and non-neoplastic cells through LPA1
    Kotaro Hama
    Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7 3 1, Hongo, Bunkyo ku, Tokyo 113 0033, Japan
    J Biol Chem 279:17634-9. 2004
    ..The present study suggests that ATX and LPA(1) represent potential targets for cancer therapy...
  59. ncbi Possible involvement of the alpha1 isoform of 5'AMP-activated protein kinase in oxidative stress-stimulated glucose transport in skeletal muscle
    Taro Toyoda
    Dept of Medicine and Clinical Science, Kyoto Univ Graduate School of Medicine, 54 Shogoin Kawaharacho, Sakyo ku, Kyoto, 606 8507, Japan
    Am J Physiol Endocrinol Metab 287:E166-73. 2004
    ....
  60. ncbi Gene expression profiles of lysophosphatidic acid-related molecules in the prostate: relevance to prostate cancer and benign hyperplasia
    Yu Zeng
    Department of Urology, Kagawa University Faculty of Medicine, Kita gun, Kagawa, Japan
    Prostate 69:283-92. 2009
    ..To elucidate gene expression profiles of lysophosphatidic acid (LPA)-related molecules in cancer, pre-cancerous lesion, and benign hyperplasia of the prostate...
  61. ncbi The non-mevalonate pathway of isoprenoid precursor biosynthesis
    William N Hunter
    Division of Biological Chemistry and Drug Discovery, College of Life Sciences, University of Dundee, Scotland, UK
    J Biol Chem 282:21573-7. 2007
    ..Detailed knowledge of the pathway may also be exploited to genetically modify microorganisms and plants to produce compounds of agricultural and medical interest...
  62. ncbi The crystal structure of human PAPS synthetase 1 reveals asymmetry in substrate binding
    Stefan Harjes
    Molekulare und Strukturelle Biophysik, Max Planck Institut fur molekulare Physiologie, Otto Hahn Str 11, and Interdisciplinary Center of Magnetic Resonance IZMR, 44227 Dortmund, Germany
    J Mol Biol 347:623-35. 2005
    ..These observations strongly indicate structural changes during the reaction cycle. Furthermore crystals soaked with ADP and APS could be prepared and the corresponding structures could be solved...
  63. ncbi From conformational chaos to robust regulation: the structure and function of the multi-enzyme RNA degradosome
    Maria W Górna
    Department of Biochemistry, University of Cambridge, Tennis Court Road, Cambridge CB2 1GA, UK
    Q Rev Biophys 45:105-45. 2012
    ..Parallels are drawn with analogous machinery in organisms from all life domains. Finally, we conjecture on roles of the degradosome as a regulatory hub for complex cellular processes...
  64. pmc X-ray structure of a hydroxylase-regulatory protein complex from a hydrocarbon-oxidizing multicomponent monooxygenase, Pseudomonas sp. OX1 phenol hydroxylase
    Matthew H Sazinsky
    Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA
    Biochemistry 45:15392-404. 2006
    ..Comparisons between the ToMOH and PHH structures provide insights into their substrate regiospecificities...
  65. pmc Thrombin activates AMP-activated protein kinase in endothelial cells via a pathway involving Ca2+/calmodulin-dependent protein kinase kinase beta
    Nadine Stahmann
    Institute of Molecular Cell Biology, Friedrich Schiller University of Jena, Nonnenplan 2, 07743 Jena, Germany
    Mol Cell Biol 26:5933-45. 2006
    ..We also demonstrate that endothelial cells possess two pathways to activate AMPK, one Ca2+/CaMKKbeta dependent and one AMP/LKB1 dependent...
  66. ncbi Human 3'-phosphoadenosine 5'-phosphosulfate synthetase (isoform 1, brain): kinetic properties of the adenosine triphosphate sulfurylase and adenosine 5'-phosphosulfate kinase domains
    Eric B Lansdon
    Department of Chemistry and Section of Molecular and Cellular Biology, University of California, One Shields Avenue, Davis, California 95616, USA
    Biochemistry 43:4356-65. 2004
    ..Chlorate and perchlorate form dead-end E.MgATP.oxyanion complexes. Phenylalanine, reported to be an inhibitor of brain ATP sulfurylase, was without effect on PAPS synthetase isoform 1...
  67. ncbi A principal role for the proteasome in endoplasmic reticulum-associated degradation of misfolded intracellular cystic fibrosis transmembrane conductance regulator
    Marina S Gelman
    Department of Biological Sciences, Stanford University, Stanford, California 94305 5020, USA
    J Biol Chem 277:11709-14. 2002
    ..Our results suggest that ubiquitin-proteasome-mediated degradation is the dominant pathway for disposal of misfolded CFTR in mammalian cells and provide new mechanistic insight into endoplasmic reticulum-associated degradation...
  68. pmc Inhibition of Schistosoma mansoni thioredoxin-glutathione reductase by auranofin: structural and kinetic aspects
    Francesco Angelucci
    Department of Biochemical Sciences A Rossi Fanelli, Sapienza University of Rome and Istituto Pasteur Fondazione Cenci Bolognetti, P le Aldo Moro 5, 00185 Rome, Italy
    J Biol Chem 284:28977-85. 2009
    ..Therefore, we propose that Sec mediates the transfer of gold from its ligands in AF to the redox-active Cys couples of TGR...
  69. ncbi Hysteresis in thioredoxin-glutathione reductase (TGR) from the adult stage of the liver fluke Fasciola hepatica
    Alberto Guevara-Flores
    Departamento de Bioquimica, Facultad de Medicina, Universidad Nacional Autonoma de Mexico, Apartado Postal 70 159, 04510, DF Mexico
    Parasitol Int 60:156-60. 2011
    ..et al. (2008) J Biol Chem 283: 17898] needs to be reevaluated...
  70. pmc Elucidation of the active conformation of the APS-kinase domain of human PAPS synthetase 1
    Nikolina Sekulic
    Department of Biochemistry and Molecular Genetics, University of Illinois at Chicago, IL 60607, USA
    J Mol Biol 367:488-500. 2007
    ..Both structures reveal extended N termini that approach the active site of the neighboring monomer. Together, these results significantly increase our understandings of how catalysis is achieved by APS-kinase...
  71. ncbi Degenerative knee joint disease in mice lacking 3'-phosphoadenosine 5'-phosphosulfate synthetase 2 (Papss2) activity: a putative model of human PAPSS2 deficiency-associated arthrosis
    Alice F Ford-Hutchinson
    Department of Biochemistry and Molecular Biology, The McCaig Center for Joint Injury and Arthritis Research, University of Calgary, Calgary, Alberta, T2N 4N1, Canada
    Osteoarthritis Cartilage 13:418-25. 2005
    ..We investigated whether loss of Papss2 activity would similarly lead to degenerative joint disease in mice...
  72. pmc Boronic acid-based inhibitor of autotaxin reveals rapid turnover of LPA in the circulation
    Harald M H G Albers
    Division of Cell Biology, Netherlands Proteomics Centre, Centre of Biomedical Genetics, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
    Proc Natl Acad Sci U S A 107:7257-62. 2010
    ..Thus, boronic acid-based small molecules hold promise as candidate drugs to target ATX...
  73. ncbi Unraveling the potential of intrinsically disordered proteins as drug targets: application to Mycobacterium tuberculosis
    Meenakshi Anurag
    G N R Knowledge Center of Genome Informatics, Institute of Genomics and Integrative Biology, CSIR, New Delhi, 110007, India
    Mol Biosyst 5:1752-7. 2009
    ..Future applications of this method can provide new insight into understanding the molecular mechanism of IDPs and their potential role as drug targets...
  74. ncbi Discovery and optimization of boronic acid based inhibitors of autotaxin
    Harald M H G Albers
    Division of Cell Biology, The Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands
    J Med Chem 53:4958-67. 2010
    ..The most potent of these compounds inhibits ATX-mediated LPC hydrolysis in the nanomolar range (IC(50) = 6 nM). The finding that ATX can be targeted by boronic acids may aid the development of ATX inhibitors for therapeutic use...
  75. ncbi A protein complex mediating mRNA degradation in Escherichia coli
    B Py
    Imperial Cancer Research Fund Laboratories, Institute of Molecular Medicine, Oxford, UK
    Mol Microbiol 14:717-29. 1994
    ..The identification of a complex which includes several activities associated with mRNA degradation has implications for the mechanisms and co-ordinated control of mRNA degradation...
  76. ncbi New lessons for combinatorial biosynthesis from myxobacteria. The myxothiazol biosynthetic gene cluster of Stigmatella aurantiaca DW4/3-1
    B Silakowski
    Gesellschaft fur Biotechnologische Forschung mbH, Mascheroder Weg 1, 38124 Braunschweig, Germany
    J Biol Chem 274:37391-9. 1999
    ..The carbon backbone of an amino acid added to the myxothiazol-acid is assumed to be removed via an unprecedented module with homology to monooxygenases within MtaG...
  77. ncbi Biochemistry of arsenic detoxification
    Barry P Rosen
    Department of Biochemistry and Molecular Biology, Wayne State University, School of Medicine, 48201, Detroit, MI, USA
    FEBS Lett 529:86-92. 2002
    ..While the overall schemes for arsenic resistance are similar in prokaryotes and eukaryotes, some of the specific proteins are the products of separate evolutionary pathways...
  78. ncbi AMP-activated protein kinase alpha2 activity is not essential for contraction- and hyperosmolarity-induced glucose transport in skeletal muscle
    Nobuharu Fujii
    Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women s Hospital and Harvard Medical School, Boston, Massachusetts 02215, USA
    J Biol Chem 280:39033-41. 2005
    ..Muscle contraction- and hyperosmolarity-induced glucose transport may be regulated by a redundant mechanism in which AMPK alpha2 is one of multiple signaling pathways...
  79. pmc Perturbation of Hsp90 interaction with nascent CFTR prevents its maturation and accelerates its degradation by the proteasome
    M A Loo
    Mayo Foundation, S C Johnson Medical Research Center, Mayo Clinic Scottsdale, 13400 E Shea Blvd, Scottsdale, AZ 85259, USA
    EMBO J 17:6879-87. 1998
    ..This is the first direct evidence of a role for Hsp90 in the maturation of a newly synthesized integral membrane protein by interaction with its cytoplasmic domains on the ER surface...
  80. pmc Muscle cachexia: current concepts of intracellular mechanisms and molecular regulation
    P O Hasselgren
    Department of Surgery, University of Cincinnati, Cincinnati, Ohio 45267 0558, USA
    Ann Surg 233:9-17. 2001
    ..To review present knowledge of intracellular mechanisms and molecular regulation of muscle cachexia...
  81. pmc The mycosubtilin synthetase of Bacillus subtilis ATCC6633: a multifunctional hybrid between a peptide synthetase, an amino transferase, and a fatty acid synthase
    E H Duitman
    Department of Genetics, Groningen Biomolecular Sciences and Biotechnology Institute, Kerklaan 30, 9751 NN Haren, The Netherlands
    Proc Natl Acad Sci U S A 96:13294-9. 1999
    ..subtilis ATCC6633, with the complete genome sequence of B. subtilis strain 168 indicates that the fengycin and mycosubtilin lipopeptide synthetase operons are exchanged between the two B. subtilis strains...
  82. ncbi Ubiquitin-dependent degradation of TGF-beta-activated smad2
    R S Lo
    Cell Biology Program, Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10021, USA
    Nat Cell Biol 1:472-8. 1999
    ..If degradation is averted, the phosphorylated Smad2 remains in the nucleus in an active state. By targeting Smad2 for destruction, TGF-beta ensures the irreversible termination of its own signalling function...
  83. ncbi Modulation of polyketide synthase activity by accessory proteins during lovastatin biosynthesis
    J Kennedy
    School of Pharmacy, Bacteriology Department, University of Wisconsin, Madison, WI 53706, USA
    Science 284:1368-72. 1999
    ..The noniterative lovastatin diketide synthase (LDKS) enzyme specifies formation of 2-methylbutyrate and interacts closely with an additional transesterase (LovD) responsible for assembling lovastatin from this polyketide and monacolin J...
  84. ncbi SUMO-1 modification of IkappaBalpha inhibits NF-kappaB activation
    J M Desterro
    School of Biomedical Science, University of St Andrews, Fife, United Kingdom
    Mol Cell 2:233-9. 1998
    ..Thus, while ubiquitination targets proteins for rapid degradation, SUMO-1 modification acts antagonistically to generate proteins resistant to degradation...
  85. ncbi The LKB1 tumor suppressor negatively regulates mTOR signaling
    Reuben J Shaw
    Department of Systems Biology, Harvard Medical School and Division of Signal Transduction, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA
    Cancer Cell 6:91-9. 2004
    ..These findings position aberrant mTOR activation at the nexus of these germline neoplastic conditions and suggest the use of mTOR inhibitors in the treatment of Peutz-Jeghers syndrome...
  86. pmc Dementia revealed: novel chromosome 6 locus for late-onset Alzheimer disease provides genetic evidence for folate-pathway abnormalities
    Adam C Naj
    Dr John T Macdonald Foundation Department of Human Genetics, John P Hussman Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, United States of America
    PLoS Genet 6:e1001130. 2010
    ..This finding is noteworthy, as MTHFD1L may play a role in the generation of methionine from homocysteine and influence homocysteine-related pathways and as levels of homocysteine are a significant risk factor for LOAD development...
  87. ncbi Activation of 5'-AMP-activated kinase is mediated through c-Src and phosphoinositide 3-kinase activity during hypoxia-reoxygenation of bovine aortic endothelial cells. Role of peroxynitrite
    Ming Hui Zou
    Vascular Research Laboratory, Department of Surgery, Graduate School of Medicine, The University of Tennessee, Knoxville, Tennessee 37920, USA
    J Biol Chem 278:34003-10. 2003
    ....
  88. ncbi Hypothalamic AMP-activated protein kinase mediates counter-regulatory responses to hypoglycaemia in rats
    S M Han
    Department of Internal Medicine, University of Ulsan College of Medicine, Poongnap dong, Songpa Gu, Seoul 138 736, South Korea
    Diabetologia 48:2170-8. 2005
    ..As AMPK is expressed in the hypothalamus, an important site of neuroendocrine regulation, the present study was undertaken to determine whether hypothalamic AMPK mediates counter-regulatory responses to hypoglycaemia...
  89. ncbi Leptin stimulates fatty-acid oxidation by activating AMP-activated protein kinase
    Yasuhiko Minokoshi
    Division of Endocrinology, Diabetes and Metabolism, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA
    Nature 415:339-43. 2002
    ..Blocking AMPK activation inhibits the phosphorylation of ACC stimulated by leptin. Our data identify AMPK as a principal mediator of the effects of leptin on fatty-acid metabolism in muscle...
  90. pmc What happens when replication and transcription complexes collide?
    Richard T Pomerantz
    The Rockefeller University, Howard Hughes Medical Institute, New York, NY, USA
    Cell Cycle 9:2537-43. 2010
    ..Here we review past and recent advances that formulate our current understanding of how the bacterial replisome deals with transcription complexes along the path of chromosome duplication...
  91. ncbi Life with carbon monoxide
    Stephen W Ragsdale
    Department of Biochemistry, Beadle Center, University of Nebraska, Lincoln, NE 68588 0664, USA
    Crit Rev Biochem Mol Biol 39:165-95. 2004
    ..The enzymes that are coupled to CODH/ACS are also described, with a focus on a corrinoid protein, a methyltransferase, and pyruvate ferredoxin oxidoreductase...
  92. ncbi Adenosine monophosphate-activated protein kinase suppresses vascular smooth muscle cell proliferation through the inhibition of cell cycle progression
    Motoyuki Igata
    Department of Metabolic Medicine, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 860 8554, Japan
    Circ Res 97:837-44. 2005
    ..These data suggest for the first time that AMPK suppresses VSMC proliferation via cell cycle regulation by p53 upregulation. Therefore, AMPK activation in VSMCs may be a therapoietic target for the prevention of vascular diseases...
  93. pmc Microtubule-assisted mechanism for functional metabolic macromolecular complex formation
    Songon An
    Department of Chemistry, Pennsylvania State University, University Park, PA 16802, USA
    Proc Natl Acad Sci U S A 107:12872-6. 2010
    ..Collectively, we propose a microtubule-assisted mechanism for functional purinosome formation in HeLa cells...
  94. ncbi Polyglutamation of methotrexate with common polymorphisms in reduced folate carrier, aminoimidazole carboxamide ribonucleotide transformylase, and thymidylate synthase are associated with methotrexate effects in rheumatoid arthritis
    Thierry Dervieux
    Prometheus Laboratories, San Diego, California, USA
    Arthritis Rheum 50:2766-74. 2004
    ....
  95. ncbi Activation of protein phosphatase 2A by palmitate inhibits AMP-activated protein kinase
    Yong Wu
    Division of Endocrinology and Diabetes, Department of Medicine, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma 73104, USA
    J Biol Chem 282:9777-88. 2007
    ..Taken together, we conclude that palmitate inhibits the phosphorylation of both AMPK and endothelial nitric-oxide synthase in endothelial cells via ceramide-dependent PP2A activation...
  96. pmc Multiple genetic modifications of the erythromycin polyketide synthase to produce a library of novel "unnatural" natural products
    R McDaniel
    Kosan Biosciences, Inc, 1450 Rollins Road, Burlingame, CA 94010, USA
    Proc Natl Acad Sci U S A 96:1846-51. 1999
    ..The manipulation of multiple biosynthetic steps in a PKS is an important milestone toward the goal of producing large libraries of unnatural natural products for biological and pharmaceutical applications...
  97. pmc Expression of autotaxin and lysophosphatidic acid receptors increases mammary tumorigenesis, invasion, and metastases
    Shuying Liu
    Department of Systems Biology, University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA
    Cancer Cell 15:539-50. 2009
    ..Thus, ATX and LPA receptors can contribute to the initiation and progression of breast cancer...
  98. pmc Recruitment to stalled replication forks of the PriA DNA helicase and replisome-loading activities is essential for survival
    Carolina B Gabbai
    Molecular Biology Program, Weill Cornell Graduate School of Medical Sciences, New York, NY, USA
    DNA Repair (Amst) 9:202-9. 2010
    ..This review focuses on the activities of PriA and its role in replication fork assembly and maintaining genomic integrity...
  99. ncbi A heterodimer of human 3'-phospho-adenosine-5'-phosphosulphate (PAPS) synthases is a new sulphate activating complex
    Daniel Grum
    Structural and Medicinal Biochemistry, Centre for Medical Biotechnology ZMB, Faculty of Biology and Geography, University of Duisburg Essen, 45117 Essen, Germany
    Biochem Biophys Res Commun 395:420-5. 2010
    ..Due to divergent catalytic efficacies of PAPSS1 and -S2, the heterodimer might be a way of regulating PAPS synthase function within mammalian cells...
  100. ncbi The FK520 gene cluster of Streptomyces hygroscopicus var. ascomyceticus (ATCC 14891) contains genes for biosynthesis of unusual polyketide extender units
    K Wu
    Kosan Biosciences Inc, Hayward, CA 94545, USA
    Gene 251:81-90. 2000
    ..Gene 169, 1-7), consistent with labeling data showing that rapamycin biosynthesis uses only malonyl and methylmalonyl extender units...
  101. ncbi A Gne knockout mouse expressing human GNE D176V mutation develops features similar to distal myopathy with rimmed vacuoles or hereditary inclusion body myopathy
    May Christine V Malicdan
    Department of Neuromuscular Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, 4 1 1 Ogawahigashi cho, Kodaira, Tokyo 187 8502, Japan
    Hum Mol Genet 16:2669-82. 2007
    ..Our findings underscore the notion that hyposialylation plays an important role in the pathomechanism of DMRV/hIBM...

Research Grants62

  1. Pyruvate Dehydrogenase E1: Structure-Function Studies
    William F Furey; Fiscal Year: 2012
    ..pathways that operate through simple diffusion of substrates and products between enzymes, PDHc and other multienzyme complexes employ substrate channeling between the E1, E2, and E3 enzymatic components...
  2. Assembly Line Biosynthesis of Bacterial Siderophores
    FRED L HEFFRON; Fiscal Year: 2012
    ..of protein-protein communication between these NRPSs that facilitates the selective interaction in the multienzyme complexes. Our results could lead to the exploration of new avenues in the fascinating field of NRPSs communication ..
  3. Structure and Mechanism of alpha-Ketoacid Decarboxylases and Dehydrogenases
    Frank Jordan; Fiscal Year: 2013
    ..coli and human pyruvate dehydrogenase multienzyme complexes. These complexes are at a key junction in metabolism of virtually all cells, converting the product of ..
  4. Artificial Metabolons: Models for proximity-driven control over multienzyme pathw
    Christine D Keating; Fiscal Year: 2012
    ..However, because these multienzyme complexes ("metabolons") are quite challenging to study in vivo or to isolate without disruption in vitro, the ..
  5. MECHANISM OF E. COLI PYRUVATE DEHYDROGENASE COMPLEX-E1
    Frank Jordan; Fiscal Year: 2004
    ..the principal investigator believes that in the coming years he and his collaborators have an opportunity to contribute to a better molecular-level understanding of this member of a very large class of related multienzyme complexes.
  6. Control of Initiation of Development in M. xanthus
    Mitchell Singer; Fiscal Year: 2006
    ..Large multienzyme complexes termed polyketide synthases and peptide synthetases, many of which are produced during starvation, ..
  7. MINORITY PREDOCTORAL FELLOWSHIP PROGRAM
    NATASHA NESBITT; Fiscal Year: 2005
    Lipoic acid, 6,8,-thioctic acid, is a key component of many multienzyme complexes that are essential in primary metabolism. It is found in most prokaryotes and eukaryotes as well as plant and animal tissue...
  8. FATTY ACID OXIDATION COMPLEXES FROM E COLI AND MAMMALS
    Song Yu Yang; Fiscal Year: 1999
    This project is aimed at gaining insights into the structure-function relationships of the beta-oxidation multienzyme complexes from prokaryotic and eukaryotic cells and ultimately at identifying genetic defect in the genes coding for ..
  9. STRUCTURE OF AMINOACYL-TRNA SYNTHETASE COMPLEXES
    MONA NORCUM; Fiscal Year: 1993
    This proposal is designed to determine the structural organization of multienzyme complexes of eukaryotic aminoacyl-tRNA synthetases...
  10. Mechanistic Studies of Lipoic Acid Synthase
    Squire J Booker; Fiscal Year: 2010
    Lipoic acid is an essential sulfur-containing cofacor that is found in several multienzyme complexes that are involved in energy metabolism...
  11. VisualSonics Vevo 770 Imaging System
    Lawrence Young; Fiscal Year: 2007
    ..Adult cardiovascular disease is the leading cause of death in this country and congenital heart disease a major cause of disability and death in children. [unreadable] [unreadable] [unreadable]..
  12. Computational Approach to Ligand Discovery for LPA GPCR and PPAR
    Abby L Parrill; Fiscal Year: 2010
    ..This research can therefore lead to new treatments for cardiovascular disease and cancer. ..
  13. Regulation of energy metabolism in the failing heart
    Raymond Russell; Fiscal Year: 2005
    ..The findings of these studies will help to characterize the defects in energy metabolism in the failing heart and aid in the design of therapies that improve energy transduction in the failing human heart. ..
  14. The Endocytic Machinery of Dendritic Spines
    Michael D Ehlers; Fiscal Year: 2010
    ....
  15. Defibrotide for the treatment of severe hepatic veno-cc*
    Paul Richardson; Fiscal Year: 2007
    ..Abstract Not Provided ..
  16. Bioorganic Chemistry of Carbon Monoxide Dehydrogenase
    PAUL LINDAHL; Fiscal Year: 2007
    ..ACS/CODH is involved in C1 metabolism and it contains a tunnel through which CO migrates, impacting the field of metabolic channeling. ..
  17. Single-particle fluorescence studies of viral fusion
    Antoine Van Oijen; Fiscal Year: 2008
    ..The proposed development and use of single-particle imaging techniques to study the fusion mechanism of influenza will lead to a more complete and dynamic picture of the various pathways involved. ..
  18. Role of AMPK in hypoglycemia-sensing in the ventromedial hypothalamus
    RORY MCCRIMMON; Fiscal Year: 2008
    ..Finally, the proposal aims to obtain data that will support the hypothesis that recurrent hypoglycemia induces mitochondrial biogenesis in the VMH, an effect that may be mediated by AMPK. ..
  19. Molecular Targets of A-beta-Induced Synaptic Dysfunction
    Michael Ehlers; Fiscal Year: 2008
    ..As such, the proposed research holds promise for the development of new therapeutic approaches for AD-associated memory loss and cognitive deficit. ..
  20. Function and regulation of cardiac uncoupling proteins
    Raymond Russell; Fiscal Year: 2009
    ..It is anticipated that the results of these studies will yield important insights into the role of UCPs in the clinically important disorders of myocardial ischemia/reperfusion and heart failure. ..
  21. Synaptic Targeting of NMDA Receptors
    Michael Ehlers; Fiscal Year: 2009
    ..Moreover, because NMDA receptors participate in the pathogenesis of a wide range of neurologic disorders, psychiatric disease, and states of addiction, these studies hold promise for the development of novel therapeutic strategies. ..
  22. Diet Therapy of Long-Chain Fatty Acid Oxidation Defects
    MELANIE GILLINGHAM; Fiscal Year: 2005
    ..abstract_text> ..
  23. Kinetic Simulations of Minimal Living Systems
    PAUL LINDAHL; Fiscal Year: 2002
    ..Simulation and animations will be critically compared to the properties of real cells. Mechanism will be modified, corrected, and embellished as deficiencies are noted and more experimental data become available. ..
  24. MECHANISM OF INHIBITION OF CFTR BY AMP-ACTIVATED KINASE
    KENNETH HALLOWS; Fiscal Year: 2005
    ..A final goal is to extend the search for functional effects of AMPK to transport systems that are closely associated with and modulated by CFTR. ..
  25. ASCB Conf:Nontraditional Functions of Ubiquitin and UbLs
    Cecile Pickart; Fiscal Year: 2002
    ..There will also be a poster session. The format of the Conference, and its small size, are designed to foster interactions among the 200 participants. ..
  26. BIACORE 3000 Biosensor
    Cecile Pickart; Fiscal Year: 2004
    ..In recognition of this fact, the Bloomberg School of Public Health has made a substantial commitment to the long-term operation and maintenance of the Biacore 3000 ..
  27. Mechanisms of ENaC Regulation by AMP-activated Kinase
    KENNETH HALLOWS; Fiscal Year: 2005
    ..abstract_text> ..
  28. Targeting Cysteine Proteases: Antiparasitic Chemotherapy
    James McKerrow; Fiscal Year: 2008
    ..No Abstract Provided. ..
  29. KALLISTATIN IN HYPERTENSION
    Julie Chao; Fiscal Year: 2008
    ..abstract_text> ..
  30. Topical Conference: Systems Biol & Metabolic Engineering
    Vassily Hatzimanikatis; Fiscal Year: 2003
    ..The conference will also provide 4 fellowships to graduate students for attending the conference. ..
  31. Alcohol abuse in a small rodent neuroAIDS model
    Johnny He; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  32. HYPOXIC STRESS MECHANISMS IN RADIATION AND CHEMOTHERAPY
    Keith Laderoute; Fiscal Year: 2009
    ..An understanding of these MTF-1-dependent properties should aid in the development of novel prognostic and new modalities for neoplastic diseases. ..
  33. GENETICS OF COCAINE INDUCED PSYCHOSIS
    Joel Gelernter; Fiscal Year: 2003
    ..This program of research will improve our understanding of the genetics underlying human brain responses to chronic cocaine exposure, thus leading to better diagnosis and treatments for cocaine dependence and other addictive disorders. ..
  34. MOLECULAR MEDIATORS OF DIABETIC RENAL HYPERTROPHY
    John Kyriakis; Fiscal Year: 2002
    ..These studies, they hope, will expand our knowledge of signal transduction in the diabetic kidney and contribute to the development of novel treatments for diabetic nephropathy using signaling components as targets. ..
  35. Prostaglandin 19-& 20-Hydroxylation by Cytochrome P450
    Bettie Sue Masters; Fiscal Year: 2005
    ..abstract_text> ..
  36. Protein Tyrosine Phosphatase 1B and Insulin Action
    Barbara Kahn; Fiscal Year: 2005
    ..Our goal is to find new therapeutic targets to reduce insulin resistance and prevent or ameliorate type 2 diabetes. ..
  37. CRYSTALLOGRAPHIC STUDIES OF ELECTRON TRANSFER PROTEINS
    Douglas Rees; Fiscal Year: 2002
    ..4. the correspondence between crystallographically defined metallocluster structures and spectroscopically assigned oxidation states in the Fe-protein and MoFe-protein. ..
  38. REGULATION OF PROTEIN TURNOVER IN SEPSIS
    Scot R Kimball; Fiscal Year: 2010
    ....
  39. GENETIC CONTROL OF NITRATE RESPIRATION IN E. COLI
    Valley J Stewart; Fiscal Year: 2010
    ..Thus, results from the model species E. coli enhance understanding for a broad range of pathogens that significantly impact public health. ..
  40. TARGETING OF BRAIN PROTEIN PHOSPHATASE 1
    ROGER COLBRAN; Fiscal Year: 2002
    ..These Aims provide novel insights into the physiological regulation of PP1, a key modulator of synaptic function. ..
  41. REGULATION OF LEUCINE OXIDATION
    Robert Harris; Fiscal Year: 2001
    ..To clone, express, and characterize BCKDH phosphatase and determine its role in regulation of the activity state of the BCKDH complex. ..
  42. MOLECULAR ANALYSIS OF TRANSCRIPTIONAL ADAPTORS
    Leonard Guarente; Fiscal Year: 2001
    ..Finally, a possible link between this coactivator and TBP will be investigated genetically and biochemically. ..
  43. 400 MHz NMR Spectrometer for Shared Use
    Craig Townsend; Fiscal Year: 2004
    ..9) investigation of the hypothesis that aromatic amino acids are required to specify a distinct conformational state by NMR spin relaxation techniques, to elucidate important parameters for protein design. ..
  44. Synaptic Glutamate Release in Drosphila
    Aaron DiAntonio; Fiscal Year: 2008
    ..The results of these experiments will provide novel and fundamental information on the mechanisms by which VGLUT contributes to the development and function of glutamatergic synapses. ..
  45. Causes and consequences of AMPK activation in the heart
    JAMES BALSCHI; Fiscal Year: 2005
    ..abstract_text> ..
  46. Modeling Oxygen Activation by Monocopper Enzyme Sites
    BENJAMIN GHERMAN; Fiscal Year: 2006
    ....
  47. Third International Mdm2 Workshop
    Ute Moll; Fiscal Year: 2005
    ..abstract_text> ..
  48. High Throughput Assay for Screening Compounds(RMI)
    James McKerrow; Fiscal Year: 2005
    ..Computational and informatics capability is in place to acquire, store and cross-reference this data, and provide access to the scientific community through an open-source website. ..
  49. Models of Familial Parkinson's Disease: PINK1
    Ted Dawson; Fiscal Year: 2006
    ....
  50. Modulation of HBV Replication by the Immunoproteasome
    Michael Robek; Fiscal Year: 2006
    ..These studies may provide a better understanding of the host factors that modulate HBV replication and that ultimately determine the outcome of infection. ..
  51. Enzymatic Cleavage of the C-N Bond in Glycine
    DAVID MERKLER; Fiscal Year: 2005
    ..abstract_text> ..
  52. REGULATION OF SUMO CONJUGATION TO THE YEAST SEPTINS
    Erica Johnson; Fiscal Year: 2005
    ..Consequently, the fundamental understanding of SUMO conjugation provided by these studies should illuminate the role of SUMO not only in yeast septin function but also in inflammation and cancer. ..
  53. Ethanol Effects on Antigen Presentation in Liver Cells
    Natalia Osna; Fiscal Year: 2006
    ..unreadable] [unreadable]..
  54. Role of H11 kinase in cardiac cell growth
    Christophe Depre; Fiscal Year: 2007
    ..These experiments will unravel novel mechanisms and signaling pathways of cardiac growth, which may result in new therapeutic avenues for both ischemic heart disease and heart failure. ..
  55. Host Protein Degradation by Schistosome Parasites
    James McKerrow; Fiscal Year: 2007
    ..abstract_text> ..
  56. LOW PH INDUCIBLE DNA REPAIR IN STREPTOCOCCUS MUTANS
    ROBERT QUIVEY; Fiscal Year: 2005
    ..mutans exonuclease, including a description of the genetic elements that participate in regulating synthesis of the enzyme and the protein(s) that function to regulate transcription of the exonuclease gene. ..
  57. Reversible and Temporally Inducible LRRK2 Knockout Mice
    Ted Dawson; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  58. Substrates of SAG-SCF E3 ligase regulate hypoxia response
    Yi Sun; Fiscal Year: 2007
    ..These initial studies will set the stage for a more detailed investigation of the mechanism of SAG mediated suppression of apoptosis. [unreadable] [unreadable]..
  59. REGULATION OF PYRUVATE DEHYDROGENASE KINASE
    Robert Harris; Fiscal Year: 2008
    ....
  60. Natural Product Model of Action Studies
    CRAIG CREWS; Fiscal Year: 2008
    ..abstract_text> ..
  61. Fluorogenic Assays for Measuring the Activity of Ceramidase and Sphingomyelinase
    Colin Ferguson; Fiscal Year: 2008
    ..These assays will help to further basic research in this growing field and potentially be used for developing new drugs for diseases such as cancer, diabetes, and Alzheimer's disease. [unreadable] [unreadable] [unreadable]..