novobiocin

Summary

Summary: An antibiotic compound derived from Streptomyces niveus. It has a chemical structure similar to coumarin. Novobiocin binds to DNA gyrase, and blocks adenosine triphosphatase (ATPase) activity. (From Reynolds, Martindale The Extra Pharmacopoeia, 30th ed, p189)

Top Publications

  1. ncbi The high-resolution crystal structure of a 24-kDa gyrase B fragment from E. coli complexed with one of the most potent coumarin inhibitors, clorobiocin
    F T Tsai
    Laboratory of Molecular Biophysics, University of Oxford, United Kingdom
    Proteins 28:41-52. 1997
  2. ncbi The entropic penalty of ordered water accounts for weaker binding of the antibiotic novobiocin to a resistant mutant of DNA gyrase: a thermodynamic and crystallographic study
    G A Holdgate
    Zeneca Pharmaceuticals, Macclesfield, Cheshire, U K
    Biochemistry 36:9663-73. 1997
  3. pmc Alteration of Escherichia coli topoisomerase IV to novobiocin resistance
    Christine D Hardy
    Department of Molecular and Cell Biology, University of California, Berkeley 94720 3204, USA
    Antimicrob Agents Chemother 47:941-7. 2003
  4. pmc Novobiocin and coumermycin inhibit DNA supercoiling catalyzed by DNA gyrase
    M Gellert
    Proc Natl Acad Sci U S A 73:4474-8. 1976
  5. pmc The baeSR two-component regulatory system activates transcription of the yegMNOB (mdtABCD) transporter gene cluster in Escherichia coli and increases its resistance to novobiocin and deoxycholate
    Natalya Baranova
    Department of Molecular and Cell Biology, University of California, Berkeley, California 94720 3206, USA
    J Bacteriol 184:4168-76. 2002
  6. ncbi The heat shock protein 90 antagonist novobiocin interacts with a previously unrecognized ATP-binding domain in the carboxyl terminus of the chaperone
    M G Marcu
    Department of Cell and Cancer Biology, Medicine Branch, NCI, National Institutes of Health, Rockville, Maryland 20850, USA
    J Biol Chem 275:37181-6. 2000
  7. pmc LVIS553 transcriptional regulator specifically recognizes novobiocin as an effector molecule
    Fernando A Pagliai
    Department of Microbiology and Cell Science, Genetics Institute, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, Florida 32610 3610, USA
    J Biol Chem 285:16921-30. 2010
  8. ncbi Modulation of Hsf1 activity by novobiocin and geldanamycin
    Renaud Conde
    Department of Anatomy and Cell Biology, College of Medicine, 107 Wiggins Rd, University of Saskatchewan, Saskatoon, SK, S7N 5E5, Canada
    Biochem Cell Biol 87:845-51. 2009
  9. ncbi Enhancing antibiotic activity: a strategy to control Acinetobacter infections
    Sasitorn Chusri
    Natural Products Research Center and Department of Microbiology, Faculty of Science, Prince of Songkla University, Hat Yai, Songkla, Thailand
    J Antimicrob Chemother 64:1203-11. 2009
  10. pmc Heterologous expression of novobiocin and clorobiocin biosynthetic gene clusters
    Alessandra S Eustáquio
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Appl Environ Microbiol 71:2452-9. 2005

Research Grants

  1. Chaperone therapeutics for the treatment of DPN
    Rick T Dobrowsky; Fiscal Year: 2013
  2. Structure of the multidrug efflux protein AcrA
    Partho Ghosh; Fiscal Year: 2006
  3. REGULATION OF MACROPHAGE DEPENDENT ANGIOGENIC ACTIVITY
    SAMUEL LEIBOVICH; Fiscal Year: 2002
  4. MODULATION OF HIGH-DOSE ALKYLATOR EFFICACY BY NOVOBIOCIN
    Michael Kennedy; Fiscal Year: 1992
  5. ROLE OF DNA REPAIR IN CISPLATIN RESISTANCE
    J Eder; Fiscal Year: 1993
  6. GENOMIC DOMAINS AND TOPOISOMERASES IN GENE REGULATION
    HAROLD MARTINSON; Fiscal Year: 1990
  7. MULTITARGET DRUGS: VERIFICATION-OF-PRINCIPLE STUDIES
    Alexander Varshavsky; Fiscal Year: 2001
  8. Ciprofloxacin resistance and compensatory Mutations.
    Julian Adams; Fiscal Year: 2004
  9. DEVELOPMENT OF NEW LIPID A BINDING AGENTS
    Paul Savage; Fiscal Year: 2002
  10. Biofilm growth and detachment of an oral pathogen
    Jeffrey Kaplan; Fiscal Year: 2007

Detail Information

Publications209 found, 100 shown here

  1. ncbi The high-resolution crystal structure of a 24-kDa gyrase B fragment from E. coli complexed with one of the most potent coumarin inhibitors, clorobiocin
    F T Tsai
    Laboratory of Molecular Biophysics, University of Oxford, United Kingdom
    Proteins 28:41-52. 1997
    Coumarin antibiotics, such as clorobiocin, novobiocin, and coumermycin A1, inhibit the supercoiling activity of gyrase by binding to the gyrase B (GyrB) subunit...
  2. ncbi The entropic penalty of ordered water accounts for weaker binding of the antibiotic novobiocin to a resistant mutant of DNA gyrase: a thermodynamic and crystallographic study
    G A Holdgate
    Zeneca Pharmaceuticals, Macclesfield, Cheshire, U K
    Biochemistry 36:9663-73. 1997
    b>Novobiocin is an antibiotic which binds to a 24 kDa fragment from the B subunit of DNA gyrase. Naturally occurring resistance arises from mutation of Arg-136 which hydrogen bonds to the coumarin ring of novobiocin...
  3. pmc Alteration of Escherichia coli topoisomerase IV to novobiocin resistance
    Christine D Hardy
    Department of Molecular and Cell Biology, University of California, Berkeley 94720 3204, USA
    Antimicrob Agents Chemother 47:941-7. 2003
    ..Coumarins, such as novobiocin, are wide-spectrum antimicrobial agents that primarily interfere with DNA gyrase...
  4. pmc Novobiocin and coumermycin inhibit DNA supercoiling catalyzed by DNA gyrase
    M Gellert
    Proc Natl Acad Sci U S A 73:4474-8. 1976
    b>Novobiocin and coumermycin are known to inhibit the replication of DNA iing of DNA catalyzed by E. coli DNA gyrase, a recently discovered enzyme that introduces negative superhelical turns into covalently circular DNA...
  5. pmc The baeSR two-component regulatory system activates transcription of the yegMNOB (mdtABCD) transporter gene cluster in Escherichia coli and increases its resistance to novobiocin and deoxycholate
    Natalya Baranova
    Department of Molecular and Cell Biology, University of California, Berkeley, California 94720 3206, USA
    J Bacteriol 184:4168-76. 2002
    Screening of random fragments of Escherichia coli genomic DNA for their ability to increase the novobiocin resistance of a hypersusceptible (Delta)acrAB mutant resulted in the isolation of a plasmid containing baeR, which codes for the ..
  6. ncbi The heat shock protein 90 antagonist novobiocin interacts with a previously unrecognized ATP-binding domain in the carboxyl terminus of the chaperone
    M G Marcu
    Department of Cell and Cancer Biology, Medicine Branch, NCI, National Institutes of Health, Rockville, Maryland 20850, USA
    J Biol Chem 275:37181-6. 2000
    ..We recently demonstrated that the gyrase inhibitor novobiocin also interacts with Hsp90, altering the affinity of the chaperone for geldanamycin and radicicol and causing in ..
  7. pmc LVIS553 transcriptional regulator specifically recognizes novobiocin as an effector molecule
    Fernando A Pagliai
    Department of Microbiology and Cell Science, Genetics Institute, Institute of Food and Agricultural Sciences, University of Florida, Gainesville, Florida 32610 3610, USA
    J Biol Chem 285:16921-30. 2010
    ..Using high throughput screening, novobiocin was found to specifically bind LVIS553 with a K(D) = 33.8 +/- 2...
  8. ncbi Modulation of Hsf1 activity by novobiocin and geldanamycin
    Renaud Conde
    Department of Anatomy and Cell Biology, College of Medicine, 107 Wiggins Rd, University of Saskatchewan, Saskatoon, SK, S7N 5E5, Canada
    Biochem Cell Biol 87:845-51. 2009
    ..Hsp90 is a known modulator of HSF1 activity, we examined the effects of two pharmacological inhibitors of Hsp90, novobiocin and geldanamycin, on HSF1 DNA-binding activity in the Xenopus oocyte model system...
  9. ncbi Enhancing antibiotic activity: a strategy to control Acinetobacter infections
    Sasitorn Chusri
    Natural Products Research Center and Department of Microbiology, Faculty of Science, Prince of Songkla University, Hat Yai, Songkla, Thailand
    J Antimicrob Chemother 64:1203-11. 2009
    ..We describe the activity of ellagic and tannic acids as adjuvants that enhance the activity of aminocoumarin antibiotics against multidrug-resistant (MDR) Acinetobacter baumannii...
  10. pmc Heterologous expression of novobiocin and clorobiocin biosynthetic gene clusters
    Alessandra S Eustáquio
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Appl Environ Microbiol 71:2452-9. 2005
    ..This method was used to express the gene clusters of the aminocoumarin antibiotics novobiocin and clorobiocin in the well-studied strains Streptomyces coelicolor and Streptomyces lividans, which, in ..
  11. pmc Intrinsic novobiocin resistance in Staphylococcus saprophyticus
    Anna A Vickers
    Antimicrobial Research Centre and Research Institute of Molecular and Cellular Biology, University of Leeds, Leeds LS2 9JT, United Kingdom
    Antimicrob Agents Chemother 51:4484-5. 2007
    Intrinsic novobiocin resistance in Staphylococcus saprophyticus was associated with expression of a novobiocin-resistant form of the drug target protein (GyrB)...
  12. ncbi Staphylococcus hominis subsp. novobiosepticus subsp. nov., a novel trehalose- and N-acetyl-D-glucosamine-negative, novobiocin- and multiple-antibiotic-resistant subspecies isolated from human blood cultures
    W E Kloos
    North Carolina State University, Raleigh 27695 7614, USA
    Int J Syst Bacteriol 48:799-812. 1998
    ..hominis (now named S. hominis subsp. hominis) by its combined characteristics of novobiocin resistance and failure to produce acid aerobically from D-trehalose and N-acetyl-D-glucosamine...
  13. ncbi Inhibitors of the HSP90 molecular chaperone: current status
    Swee Sharp
    Signal Transduction and Molecular Pharmacology Team, Cancer Research UK, Centre for Cancer Therapeutics, The Institute of Cancer Research, Haddow Laboratories, Sutton, Surrey, SM2 5NG, United Kingdom
    Adv Cancer Res 95:323-48. 2006
    ..Thus, it is not surprising that new HSP90 agents are under development against this novel target for cancer therapy and several show promise...
  14. ncbi Novobiocin: redesigning a DNA gyrase inhibitor for selective inhibition of hsp90
    Joseph A Burlison
    Department of Medicinal Chemistry, The University of Kansas, 1251 Wescoe Hall Drive, Malott Hall 4070, Lawrence, Kansas 66045 7563, USA
    J Am Chem Soc 128:15529-36. 2006
    b>Novobiocin is a member of the coumermycin family of antibiotics and is a well-established inhibitor of DNA gyrase...
  15. pmc A novel function of novobiocin: disrupting the interaction of HIF 1α and p300/CBP through direct binding to the HIF1α C-terminal activation domain
    Donglu Wu
    College of Life Science, Jilin University, Changchun, Jilin, China
    PLoS ONE 8:e62014. 2013
    ..Here, we document, for the first time, that the aminocoumarin antibiotic, novobiocin, directly blocks the protein-protein interaction between the HIF1α C-terminal activation domain (CTAD) and the ..
  16. pmc tRNA synthetase mutants of Escherichia coli K-12 are resistant to the gyrase inhibitor novobiocin
    M Jovanovic
    Institute of Molecular Genetics and Genetic Engineering, 11001 Belgrade, Yugoslavia
    J Bacteriol 181:2979-83. 1999
    ..we demonstrated that mutations in the genes cysB, cysE, and cls (nov) affect resistance of Escherichia coli to novobiocin (J. Rakonjac, M. Milic, and D. J. Savic, Mol. Gen. Genet. 228:307-311, 1991; R. Ivanisevic, M. Milic, D...
  17. pmc Null mutation of the dam or seqA gene suppresses temperature-sensitive lethality but not hypersensitivity to novobiocin of muk null mutants
    T Onogi
    Department of Molecular Cell Biology, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto 862 0976, Japan
    J Bacteriol 182:5898-901. 2000
    ..We show here that the associated muk null mutations cause hypersensitivity to novobiocin. Null mutation of either dam or seqA suppressed partially the temperature-sensitive lethality but failed to ..
  18. pmc Mutants suppressing novobiocin hypersensitivity of a mukB null mutation
    Shun Adachi
    Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Konoe, Yoshida, Sakyo, Kyoto 606 8501, Japan
    J Bacteriol 185:3690-5. 2003
    ..A mukB null mutant is hypersensitive to the DNA gyrase inhibitor novobiocin. In this work, we isolated mutants suppressing the novobiocin hypersensitivity of the mukB null mutation...
  19. ncbi Initial characterization of novobiocic acid noviosyl transferase activity of NovM in biosynthesis of the antibiotic novobiocin
    Caren L Freel Meyers
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Biochemistry 42:4179-89. 2003
    The aminocoumarin class of antibiotics, exemplified by novobiocin, is composed of tripartite l-noviosylaminocoumarin prenylbenzoate natural products...
  20. ncbi Novobiocin biosynthesis: inactivation of the putative regulatory gene novE and heterologous expression of genes involved in aminocoumarin ring formation
    Alessandra S Eustáquio
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Arch Microbiol 180:25-32. 2003
    The left ends of the biosynthetic gene clusters of novobiocin ( nov), clorobiocin ( clo) and coumermycin A(1) ( cou) from Streptomyces spheroides (syn. S. caeruleus) NCIMB 11891, S. roseochromogenes var. oscitans DS 12.976 and S...
  21. ncbi The 1.6-A resolution crystal structure of NovW: a 4-keto-6-deoxy sugar epimerase from the novobiocin biosynthetic gene cluster of Streptomyces spheroides
    Piotr Jakimowicz
    Department of Molecular Microbiology, John Innes Centre, Norwich, United Kingdom
    Proteins 63:261-5. 2006
  22. pmc Synthesis and biological evaluation of arylated novobiocin analogs as Hsp90 inhibitors
    Bhaskar Reddy Kusuma
    Department of Medicinal Chemistry, The University of Kansas, Lawrence, KS 66045 7563, USA
    Bioorg Med Chem Lett 21:7170-4. 2011
    b>Novobiocin analogs lacking labile glycosidic ether have been designed, synthesized and evaluated for Hsp90 inhibitory activity...
  23. ncbi Development and efficacy of a novobiocin-resistant Streptococcus iniae as a novel vaccine in Nile tilapia (Oreochromis niloticus)
    Julia W Pridgeon
    Aquatic Animal Health Research Unit, USDA ARS, 990 Wire Road, Auburn, AL 36832 United States
    Vaccine 29:5986-93. 2011
    ..iniae vaccine was developed from a virulent strain of Streptococcus iniae (ISET0901) through selection for novobiocin resistance (named ISNO)...
  24. ncbi Coumarin formation in novobiocin biosynthesis: beta-hydroxylation of the aminoacyl enzyme tyrosyl-S-NovH by a cytochrome P450 NovI
    H Chen
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
    Chem Biol 8:301-12. 2001
    BACKGROUND: Coumarin group antibiotics, such as novobiocin, coumermycin A1 and clorobiocin, are potent inhibitors of DNA gyrase...
  25. pmc Novobiocin is a potent inhibitor for human organic anion transporters
    Peng Duan
    Department of Pharmaceutics, Rutgers, The State University of New Jersey, Piscataway, NJ 08854, USA
    Drug Metab Dispos 37:1203-10. 2009
    ..Previous studies have shown that novobiocin, an inhibitor for breast cancer resistance proteins (BCRP), inhibited organic anion transport...
  26. ncbi New novobiocin analogues as antiproliferative agents in breast cancer cells and potential inhibitors of heat shock protein 90
    Gaëlle Le Bras
    University of Paris Sud, CNRS, BioCIS UMR 8076, Laboratoire de Chimie Therapeutique, and University of Paris Sud, 5 rue J B Clement, Chatenay Malabry, France
    J Med Chem 50:6189-200. 2007
    ..Investigation of novobiocin analogues lacking the noviose moiety as novel inhibitors of hsp90 was carried out...
  27. pmc Crystal structures of Escherichia coli topoisomerase IV ParE subunit (24 and 43 kilodaltons): a single residue dictates differences in novobiocin potency against topoisomerase IV and DNA gyrase
    Steven Bellon
    Vertex Pharmaceuticals Incorporated, Cambridge, Massachusetts 02139, USA
    Antimicrob Agents Chemother 48:1856-64. 2004
    ..0-A resolution and a 24-kDa N-terminal fragment of the ParE subunit complexed with novobiocin at 2.1-A resolution...
  28. pmc Identification of the novobiocin biosynthetic gene cluster of Streptomyces spheroides NCIB 11891
    M Steffensky
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, 72076 Tubingen, Germany
    Antimicrob Agents Chemother 44:1214-22. 2000
    The novobiocin biosynthetic gene cluster from Streptomyces spheroides NCIB 11891 was cloned by using homologous deoxynucleoside diphosphate (dNDP)-glucose 4,6-dehydratase gene fragments as probes. Double-stranded sequencing of 25...
  29. ncbi Development of novobiocin analogues that manifest anti-proliferative activity against several cancer cell lines
    Joseph A Burlison
    Department of Medicinal Chemistry, 1251 Wescoe Hall Drive, Malott 4070, The University of Kansas, Lawrence, Kansas 66045 7563, USA
    J Org Chem 73:2130-7. 2008
    Recent studies have shown that the DNA gyrase inhibitor, novobiocin, binds to a previously unrecognized ATP-binding site located at the C-terminus of Hsp90 and induces degradation of Hsp90-dependent client proteins at approximately 700 ..
  30. pmc KU135, a novel novobiocin-derived C-terminal inhibitor of the 90-kDa heat shock protein, exerts potent antiproliferative effects in human leukemic cells
    Shary N Shelton
    Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS, USA
    Mol Pharmacol 76:1314-22. 2009
    ..Here, we investigated the extent to which a novel novobiocin-derived C-terminal Hsp90 inhibitor, designated KU135, induced antiproliferative effects in Jurkat T-lymphocytes...
  31. pmc Characterization of a novel novobiocin analogue as a putative C-terminal inhibitor of heat shock protein 90 in prostate cancer cells
    Shawna B Matthews
    Department of Urology, University of Kansas Medical Center, Kansas City, Kansas 66160, USA
    Prostate 70:27-36. 2010
    ..Previously, we reported the development of novobiocin analogues designed to inhibit the C-terminal portion of Hsp90, which demonstrated the ability to decrease client ..
  32. pmc Synergy between polyethylenimine and different families of antibiotics against a resistant clinical isolate of Pseudomonas aeruginosa
    Hayssam Khalil
    Faculty of Life Sciences, Northwestern Polytechnical University, Xi an, Shaanxi 710072, People s Republic of China
    Antimicrob Agents Chemother 52:1635-41. 2008
    ..250 nM, PEI (10 kDa) was not directly bactericidal or bacteriostatic; but when it was used in combination with novobiocin, ceftazidime, ampicillin, ticarcillin, carbenicillin, piperacillin, cefotaxime, chloramphenicol, rifampin, or ..
  33. ncbi Hsp90 inhibitors identified from a library of novobiocin analogues
    Xiao Ming Yu
    Department of Medicinal Chemistry and The Center for Protein Structure and Function, The University of Kansas, 1251 Wescoe Hall Drive, Malott 4070, Lawrence, Kansas 66045 7582, USA
    J Am Chem Soc 127:12778-9. 2005
    b>Novobiocin is a C-terminal inhibitor of the Hsp90 protein folding machinery, which is responsible for the conformational maturation of numerous proteins involved in cancer growth and survival...
  34. pmc Active-site residues of Escherichia coli DNA gyrase required in coupling ATP hydrolysis to DNA supercoiling and amino acid substitutions leading to novobiocin resistance
    Christian H Gross
    Vertex Pharmaceuticals Incorporated, Cambridge, Massachusetts 02139, USA
    Antimicrob Agents Chemother 47:1037-46. 2003
    ..Amino acids in proximity to bound nonhydrolyzable ATP analog (AMP. PNP) or novobiocin in the gyrase B (GyrB) subunit crystal structures were examined for their roles in enzyme function and ..
  35. pmc Novobiocin and additional inhibitors of the Hsp90 C-terminal nucleotide-binding pocket
    Alison Donnelly
    Department of Medicinal Chemistry, 1251 Wescoe Hall Drive, The University of Kansas, Lawrence, KS 66045 7563, USA
    Curr Med Chem 15:2702-17. 2008
    ..This C-terminal nucleotide binding pocket has been shown to not only bind ATP, but cisplatin, novobiocin, epilgallocatechin-3-gallate (EGCG) and taxol...
  36. ncbi Influence of prepartum pirlimycin hydrochloride or penicillin-novobiocin therapy on mastitis in heifers during early lactation
    S P Oliver
    Department of Animal Science and the Food Safety Center of Excellence, Institute of Agriculture, The University of Tennessee, Knoxville 37996, USA
    J Dairy Sci 87:1727-31. 2004
    ..in 2 dairy research herds to determine whether prepartum therapy of heifer mammary glands with penicillin-novobiocin or pirlimycin hydrochloride was effective for reducing the percentage of heifers and mammary quarters infected ..
  37. ncbi Reversal of breast cancer resistance protein (BCRP/ABCG2)-mediated drug resistance by novobiocin, a coumermycin antibiotic
    Ken Shiozawa
    Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan
    Int J Cancer 108:146-51. 2004
    ..b>Novobiocin, a coumermycin antibiotic, is known to enhance anticancer drug sensitivity of cancer cells in vitro and in vivo, ..
  38. ncbi Novobiocin induces apoptosis-like cell death in topoisomerase II over-expressing arsenite resistant Leishmania donovani
    Gaganmeet Singh
    Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Sec 67, S A S Nagar, Punjab 160062, India
    Mol Biochem Parasitol 141:57-69. 2005
    ..Here we report that the arsenite resistant strain of L. donovani promastigotes shows cross-resistance to novobiocin, a catalytic inhibitor of topoisomerase II, with IC50 value of 320 microg ml-1 as compared with 242 microg ml-1 ..
  39. pmc Ser-127-to-Leu substitution in the DNA gyrase B subunit of Streptococcus pneumoniae is implicated in novobiocin resistance
    R Munoz
    Unidad de Genetica Bacteriana, Instituto de Salud Carlos III, Majadahonda, Spain
    J Bacteriol 177:4166-70. 1995
    ..The same amino acid substitution (Ser-127 to Leu) confers novobiocin resistance on four isolates of S. pneumoniae...
  40. pmc Gene expression changes triggered by exposure of Haemophilus influenzae to novobiocin or ciprofloxacin: combined transcription and translation analysis
    H Gmuender
    F. Hoffmann-La Roche Ltd, Pharmaceuticals Division, CH-4070 Basel, Switzerland
    Genome Res 11:28-42. 2001
    ..DNA gyrase inhibitors of two different functional classes were used. Novobiocin, as a representative of one class, inhibits the ATPase activity of the enzyme, thereby indirectly changing the ..
  41. ncbi Novobiocin induces a distinct conformation of Hsp90 and alters Hsp90-cochaperone-client interactions
    Bo Geon Yun
    Department of Biochemistry and Molecular Biology, Oklahoma State University, Stillwater, Oklahoma 74078 3035, USA
    Biochemistry 43:8217-29. 2004
    ..Recently, novobiocin has been shown to bind to a second nucleotide binding site located within the C-terminal domain of Hsp90...
  42. ncbi Modulation of chaperone function and cochaperone interaction by novobiocin in the C-terminal domain of Hsp90: evidence that coumarin antibiotics disrupt Hsp90 dimerization
    Rudi K Allan
    Laboratory for Molecular Endocrinology, Western Australian Institute for Medical Research, Queen Elizabeth II Medical Centre, The University of Western Australia, Hospital Avenue, Nedlands, WA 6009, Australia
    J Biol Chem 281:7161-71. 2006
    ..contributes to the Hsp90 interaction with the immunophilin cochaperones and corresponds to the binding site for novobiocin, a coumarin-related Hsp90 inhibitor...
  43. pmc Neuroprotective activity and evaluation of Hsp90 inhibitors in an immortalized neuronal cell line
    Yuanming Lu
    The Department of Medicinal Chemistry, The University of Kansas, Lawrence, KS 66045 7563, USA
    Bioorg Med Chem 17:1709-15. 2009
    ..and cytotoxicity resulting from exposure to Abeta peptides to evaluate the neuroprotective properties of novel novobiocin analogues and established Hsp90 inhibitors...
  44. ncbi Identification of the CysB-regulated gene, hslJ, related to the Escherichia coli novobiocin resistance phenotype
    Mirjana Lilic
    Institute of Molecular Genetics and Genetic Engineering, PO Box 446, 11001, Belgrade, Serbia and Montenegro, Yugoslavia
    FEMS Microbiol Lett 224:239-46. 2003
    ..and Salmonella, along with being auxotrophs for the cysteine, exhibit increased resistance to the antibiotics novobiocin (Nov) and mecillinam...
  45. pmc The design, synthesis, and evaluation of coumarin ring derivatives of the novobiocin scaffold that exhibit antiproliferative activity
    Alison C Donnelly
    Department of Medicinal Chemistry, 1251 Wescoe Hall Drive, Malott 4070, The University of Kansas, Lawrence, Kansas 66045 7563, USA
    J Org Chem 73:8901-20. 2008
    b>Novobiocin, a known DNA gyrase inhibitor, binds to a nucleotide-binding site located on the Hsp90 C-terminus and induces degradation of Hsp90-dependent client proteins at approximately 700 microM in breast cancer cells (SKBr3)...
  46. pmc Optimizing glycosyltransferase specificity via "hot spot" saturation mutagenesis presents a catalyst for novobiocin glycorandomization
    Gavin J Williams
    Laboratory for Biosynthetic Chemistry, Pharmaceutical Sciences Division, School of Pharmacy, National Cooperative Drug Discovery Program, University of Wisconsin Madison, 777 Highland Avenue, Madison, WI 53705, USA
    Chem Biol 15:393-401. 2008
    ..Incredibly, even in the absence of a high-throughput screen for novobiocic acid glycosylation, this approach rapidly led to improvements in the desired catalytic activity of several hundred-fold...
  47. ncbi Novobiocin-induced ultrastructural changes and antagonism of DNA synthesis in Trypanosoma cruzi amastigotes growing in cell-free medium
    R L Kerschmann
    Department of Pathology, Massachusetts General Hospital, Boston 02114
    J Protozool 36:14-20. 1989
    The antimicrobial agent novobiocin, an inhibitor of the bacterial enzyme topoisomerase II (DNA gyrase), is known to antagonize Trypanosoma cruzi amastigotes growing in cell-free medium...
  48. pmc Engineering an antibiotic to fight cancer: optimization of the novobiocin scaffold to produce anti-proliferative agents
    Huiping Zhao
    Department of Medicinal Chemistry, The University of Kansas, Lawrence, KS 66045 7563, USA
    J Med Chem 54:3839-53. 2011
    Development of the DNA gyrase inhibitor, novobiocin, into a selective Hsp90 inhibitor was accomplished through structural modifications to the amide side chain, coumarin ring, and sugar moiety...
  49. pmc C-terminal heat shock protein 90 inhibitor decreases hyperglycemia-induced oxidative stress and improves mitochondrial bioenergetics in sensory neurons
    Liang Zhang
    Department of Pharmacology and Toxicology, The University of Kansas, Lawrence, Kansas 66045, United States
    J Proteome Res 11:2581-93. 2012
    ..KU-32 is a novobiocin-based, C-terminal inhibitor of the molecular chaperone, heat shock protein 90 (Hsp90)...
  50. ncbi Characterization of the aminocoumarin ligase SimL from the simocyclinone pathway and tandem incubation with NovM,P,N from the novobiocin pathway
    Michelle Pacholec
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Biochemistry 44:4949-56. 2005
    ..Unlike the antibiotics novobiocin, clorobiocin, and coumermycin A(1), the phenolic hydroxyl group of the aminocoumarin in simocyclinone is not ..
  51. ncbi Staphylococcus stepanovicii sp. nov., a novel novobiocin-resistant oxidase-positive staphylococcal species isolated from wild small mammals
    Tomasz Hauschild
    Department of Microbiology, Institute of Biology, University of Bialystok, Swierkowa 20 B, 15 950 Bialystok, Poland
    Syst Appl Microbiol 33:183-7. 2010
    Five novobiocin-resistant and oxidase-positive staphylococcal strains were isolated from wild small mammals...
  52. pmc Nucleotide sequence, mutational analysis, transcriptional start site, and product analysis of nov, the gene which affects Escherichia coli K-12 resistance to the gyrase inhibitor novobiocin
    R Ivanisevic
    Institute of Molecular Genetics and Genetic Engineering, Belgrade, Yugoslavia
    J Bacteriol 177:1766-71. 1995
    ..the existence of a gene locus, nov, which affects resistance of Escherichia coli K-12 to the gyrase inhibitor novobiocin and, to a lesser degree, coumermycin (J. Rakonjac, M. Milic, D. Ajdic, D. Santos, R. Ivanisevic, and D. J...
  53. ncbi A library of noviosylated coumarin analogues
    Yung Tzung Huang
    Department of Medicinal Chemistry and The Center for Chemical Methodologies and Library Development, The University of Kansas, 1251 Wescoe Hall Drive, Malott Hall 4070, Lawrence, Kansas 66045 7563, USA
    J Org Chem 72:3609-13. 2007
    The DNA gyrase inhibitor, novobiocin, was recently shown to inhibit Hsp90 via a previously unrecognized C-terminal ATP-binding site...
  54. ncbi Novobiocin decreases SMYD3 expression and inhibits the migration of MDA-MB-231 human breast cancer cells
    Xue Gang Luo
    China Pharmaceutical University, Nanjing, China
    IUBMB Life 62:194-9. 2010
    ..In this study, we further found that novobiocin, a HSP90 inhibitor, could decrease the expression of SMYD3 and dose dependently inhibit the proliferation and ..
  55. ncbi S-Adenosylmethionine (SAM) and antibiotic biosynthesis: effect of external addition of SAM and of overexpression of SAM biosynthesis genes on novobiocin production in Streptomyces
    Xin Qing Zhao
    Pharmaceutical Institute, Eberhard Karls Universitat Tubingen, Germany
    Arch Microbiol 192:289-97. 2010
    ..SAM addition, and of the expression of SAM biosynthetic genes, on the production of the aminocoumarin antibiotic novobiocin in the heterologous producer strain Streptomyces coelicolor M512 (nov-BG1)...
  56. ncbi A coumermycin/novobiocin-regulated gene expression system
    Hui fen Zhao
    Mammalian Cell Genetics, Biotechnology Research Institute, National Research Council of Canada, Montreal, Quebec, Canada H4P 2R2
    Hum Gene Ther 14:1619-29. 2003
    ..More significantly, addition of novobiocin, an antagonist of coumermycin, promptly switched off expression of the gene by abolishing coumermycin-induced ..
  57. ncbi Synthesis and biological activity of simplified denoviose-coumarins related to novobiocin as potent inhibitors of heat-shock protein 90 (hsp90)
    Christine Radanyi
    Univ Paris Sud, CNRS, UMR 8612, Laboratoire de Pharmacologie Cellulaire et Moléculaire des Anticancéreux, Faculte de Pharmacie, IFR 141, 5 rue J B Clement, Chatenay Malabry F 92296, France
    Bioorg Med Chem Lett 18:2495-8. 2008
    ..In cell proliferation assay, the most active compound 5g was approximately 8 times more potent than the parent novobiocin natural compound.
  58. ncbi Supplementation of enrichment broths by novobiocin for detecting Shiga toxin-producing Escherichia coli from food: a controversial use
    A Vimont
    Unité de Microbiologie Alimentaire et Prévisionnelle, Ecole Nationale Veterinaire de Lyon, France
    Lett Appl Microbiol 44:326-31. 2007
    To investigate the assumption that usage of novobiocin (20 mg l(-1)) in Shiga toxin-producing Escherichia coli (STEC) enrichment broths could achieve false-negative results.
  59. ncbi Disruption of the Bcr-Abl/Hsp90 protein complex: a possible mechanism to inhibit Bcr-Abl-positive human leukemic blasts by novobiocin
    L X Wu
    Deparment of Pharmacology, Institute of Clinical Pharmacology, Fujian Medical University, Fuzhou, PR China
    Leukemia 22:1402-9. 2008
    ..Because Bcr-Abl TK is chaperoned by Hsp90 (90 kDa heat-shock protein), we investigated the effects of novobiocin (NB), an Hsp90 C-terminal inhibitor, on the viability of the Bcr-Abl-positive human leukemia cells HL-60/Bcr-Abl ..
  60. ncbi TPU-0031-A and B, new antibiotics of the novobiocin group produced by Streptomyces sp. TP-A0556
    T Sasaki
    Biotechnology Research Center, Toyama Prefectural University, Kosugi, Japan
    J Antibiot (Tokyo) 54:441-7. 2001
    ..Spectroscopic analyses showed that TPU-0031-A and B were 7'-demethylnovobiocin and 5"-demethylnovobiocin, respectively. These compounds showed antibiotic activity against Gram-positive and -negative bacteria...
  61. ncbi Enhancement of the activity of novobiocin against Escherichia coli by lactoferrin
    M S Sanchez
    Upjohn Company, Kalamazoo, MI 49001, USA
    J Dairy Sci 82:494-9. 1999
    The activity of novobiocin against Escherichia coli ATCC 25922 and three E. coli strains that were isolated from cases of bovine mastitis was determined in timekill studies in the presence of bovine lactoferrin...
  62. ncbi Crystallization of the 43 kDa ATPase domain of Thermus thermophilus gyrase B in complex with novobiocin
    V Lamour
    Institut de Génétique et de Biologie Moléculaire, CNRS INSERM ULP, BP 10142, 1 rue Laurent Fries, 67404 Illkirch Cedex, France
    Acta Crystallogr D Biol Crystallogr 58:1376-8. 2002
    ..Crystals of the 43 kDa domain in complex with novobiocin, one of the most potent inhibitors of bacterial topoisomerases, were obtained...
  63. pmc Identity of the Escherichia coli cls and nov genes
    B E Tropp
    Department of Chemistry and Biochemistry, Queens College CUNY, Flushing 11367, USA
    J Bacteriol 177:5155-7. 1995
    cls and nov mutants have similar increased sensitivities to novobiocin and reduced levels of cardiolipin, both of which can be corrected by plasmid-borne copies of either wild-type gene...
  64. ncbi NovJ/NovK catalyze benzylic oxidation of a beta-hydroxyl tyrosyl-S-pantetheinyl enzyme during aminocoumarin ring formation in novobiocin biosynthesis
    M Pacholec
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA
    Biochemistry 44:12819-26. 2005
    ..We also have identified a residue in NovJ that when mutated results in a 50-fold reduction in catalytic activity...
  65. ncbi A 4.2 kDa synthetic peptide as a potential probe to evaluate the antibacterial activity of coumarin drugs
    Andreza C Scatigno
    Departamento de Bioquímica e Tecnologia Química, Instituto de Quimica, Universidade Estadual Paulista, Araraquara, Sao Paulo, Brazil
    J Pept Sci 10:566-77. 2004
    ..The peptide mimic binds to novobiocin (Ka = 1.4+/-0.3 x 10(5) M(-1)), plasmid (Ka = 1.6+/-0.5 x 10(6) M(-1)) and ATP (Ka = 1.9+/-50...
  66. ncbi CouO and NovO: C-methyltransferases for tailoring the aminocoumarin scaffold in coumermycin and novobiocin antibiotic biosynthesis
    Michelle Pacholec
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Biochemistry 44:14969-76. 2005
    During the biosynthesis of the streptomycete aminocoumarin antibiotics novobiocin and the dimeric coumermycin A(1), the bicyclic coumarin scaffold is C-methylated adjacent to the phenolic oxygen...
  67. pmc Thioredoxin can influence gene expression by affecting gyrase activity
    Kuanyu Li
    Institut fur Mikrobiologie und Molekularbiologie, University of Giessen, Heinrich Buff Ring 26 32, D 35392 Giessen, Germany
    Nucleic Acids Res 32:4563-75. 2004
    ..Furthermore, inhibition of gyrase activity strongly reduces puf and puc expression. Our results reveal a new signaling pathway by which oxygen can affect the expression of bacterial genes...
  68. ncbi Nuclear gyrB encodes a functional subunit of the Plasmodium falciparum gyrase that is involved in apicoplast DNA replication
    E V S Raghu Ram
    Division of Molecular and Structural Biology, Central Drug Research Institute, Post Box 173, Chattar Manzil, Mahatma Gandhi Marg, Lucknow 226001, India
    Mol Biochem Parasitol 154:30-9. 2007
    ..The ATPase activity of PfGyrB was inhibited by novobiocin that also caused parasite death in culture...
  69. ncbi The omlA gene is involved in multidrug resistance and its expression is inhibited by coumarins in Xanthomonas campestris pv. phaseoli
    Mayuree Fuangthong
    Laboratory of Biotechnology, Chulabhorn Research Institute, Lak Si, Bangkok 10210, Thailand
    Arch Microbiol 189:211-8. 2008
    ..phaseoli was isolated and characterized. An omlA insertion mutant showed an increased susceptibility to novobiocin and coumermycin, antibiotics with gyrase inhibitor activity. The omlA mutant accumulated novobiocin...
  70. ncbi New aminocoumarin antibiotics from a cloQ-defective mutant of the clorobiocin producer Streptomyces roseochromogenes DS12.976
    Anja Freitag
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universität Tübingen Auf der Morgenstelle 8, 72076 Tubingen, Germany
    J Antibiot (Tokyo) 57:205-9. 2004
    ..Declovanillobiocin lacks the chlorine atom at the aminocoumarin ring. All three compounds had lower antibiotic activity against Bacillus subtilis than clorobiocin...
  71. pmc Characterization of the DNA gyrase from the thermoacidophilic archaeon Thermoplasma acidophilum
    Kan Yamashiro
    Department of Molecular Biology, Tokyo University of Pharmacy and Life Science, 1432 1 Horinouchi, Hachioji, Tokyo 192 0392, Japan
    J Bacteriol 187:8531-6. 2005
    Thermoplasma acidophilum is sensitive to the antibiotic drug novobiocin, which inhibits DNA gyrase. We characterized DNA gyrases from T. acidophilum strains in vitro...
  72. ncbi Flagellar and global gene regulation in Helicobacter pylori modulated by changes in DNA supercoiling
    Fang Ye
    Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Carl Neuberg Strasse 1, D 30625 Hanover, Germany
    Int J Med Microbiol 297:65-81. 2007
    ..H. pylori DNA supercoiling, monitored by a reporter plasmid, was relaxed by novobiocin, an inhibitor of DNA gyrase...
  73. pmc Structure-activity relationships of aminocoumarin-type gyrase and topoisomerase IV inhibitors obtained by combinatorial biosynthesis
    Ruth H Flatman
    Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Colney, Norwich, NR4 7UH, United Kingdom
    Antimicrob Agents Chemother 50:1136-42. 2006
    b>Novobiocin and clorobiocin are gyrase inhibitors produced by Streptomyces strains...
  74. pmc Mutation at the "exit gate" of the salmonella gyrase a subunit suppresses a defect in the gyrase B subunit
    Anne Béatrice Blanc-Potard
    Avenir team Institut National de la Santé et de la Recherche Médicale, Unité 431, Faculte de Medecine, CS 83021, Avenue J F Kennedy, 30908 NIMES Cedex 02, France
    J Bacteriol 187:6841-4. 2005
    ..gyrB651) confers resistance to nalidixic acid and causes reduced DNA superhelicity and hypersensitivity to novobiocin. Selection for novobiocin resistance allowed isolation of a mutation in the gyrA gene (allele gyrA659), a T467S ..
  75. ncbi Increased negative superhelical density in vivo enhances the genetic instability of triplet repeat sequences
    Marek Napierala
    Institute of Biosciences and Technology, Center for Genome Research, Texas A and M University System Health Science Center, Houston, 77030 3303, USA
    J Biol Chem 280:37366-76. 2005
    ..the utilization of topoisomerase I and/or DNA gyrase mutants, second, the specific inhibition of DNA gyrase by novobiocin, and third, the genetic removal of the HU protein, thus lowering the negative supercoil density (-sigma)...
  76. pmc Contribution of the ATP binding site of ParE to susceptibility to novobiocin and quinolones in Streptococcus pneumoniae
    Philippe Dupont
    INSERM E0004, Laboratoire de Recherche Moleculaire sur les Antibiotiques, 15, rue de l Ecole de Medecine, Universite Paris VI, 75270 Paris Cedex 06, France
    J Bacteriol 187:1536-40. 2005
    ..site of the ParE subunit of topoisomerase IV was shown to confer quinolone resistance and hypersensitivity to novobiocin when associated with an S84F change in the A subunit of DNA gyrase...
  77. ncbi The effect of low-temperature-induced DNA supercoiling on the expression of the desaturase genes in synechocystis
    D A Los
    Institute of Plant Physiology, Russian Academy of Sciences, Botanicheskaya Street 35, Moscow, 127276 Russia
    Cell Mol Biol (Noisy-le-grand) 50:605-12. 2004
    ..Upon decrease in temperature, the degree of DNA supercoiling increased in this region. Novobiocin, an inhibitor of the DNA gyrase, prevented low-temperature-induced changes in DNA supercoiling and affected the ..
  78. pmc Gyrase inhibitors and thymine starvation disrupt the normal pattern of plasmid RK2 localization in Escherichia coli
    Erik P Johnson
    Center for Molecular Genetics and Division of Biological Sciences, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093 0322, USA
    J Bacteriol 187:3538-47. 2005
    ..The various treatments included thymine starvation and the addition of the gyrase inhibitors nalidixic acid and novobiocin. In each case, localization of plasmid clusters at the preferred positions was disrupted but the plasmids ..
  79. pmc Accumulation of mutations in both gyrB and parE genes is associated with high-level resistance to novobiocin in Staphylococcus aureus
    Mika Fujimoto-Nakamura
    Pharmacology and Microbiology Research Laboratories, Dainippon Pharmaceutical Co, Ltd, Enoki 33 94, Suita, Osaka 564 0053, Japan
    Antimicrob Agents Chemother 49:3810-5. 2005
    Coumarin-resistant mutants of Staphylococcus aureus were isolated by three-step selection with novobiocin at different concentrations...
  80. pmc Crystallization and preliminary X-ray analysis of the aromatic prenyltransferase CloQ from the clorobiocin biosynthetic cluster of Streptomyces roseochromogenes
    Sascha Keller
    Department of Biological Chemistry, John Innes Centre, Norwich NR4 7UH, England, UK
    Acta Crystallogr Sect F Struct Biol Cryst Commun 62:1153-5. 2006
    ..6%. CloQ is involved in the biosynthesis of the aminocoumarin antibiotic clorobiocin, which targets the essential bacterial enzyme DNA gyrase...
  81. ncbi Protein A gene expression is regulated by DNA supercoiling which is modified by the ArlS-ArlR two-component system of Staphylococcus aureus
    Benedicte Fournier
    Laboratoire des Listeria, Institut Pasteur, 25 rue du Docteur Roux, 75724 Paris Cedex 15, France
    Microbiology 150:3807-19. 2004
    ..down-regulated by high osmolarity (1 M NaCl, 1 M KCl or 1 M sucrose) in the wild-type strain and upregulated by novobiocin (a DNA gyrase inhibitor that relaxes DNA)...
  82. ncbi Mass spectrometric pathway monitoring of secondary metabolites: systematic analysis of culture extracts of Streptomyces species
    Bernd Kammerer
    Department of Clinical Pharmacology, Institute of Pharmacology and Toxicology, University Hospital Tubingen, 72076 Tubingen, Germany
    Anal Biochem 335:17-29. 2004
    ..Streptomyces rishiriensis, and Streptomyces roseochromogenes are producers of the aminocoumarin-type antibiotics novobiocin, coumermycin A(1), and clorobiocin, respectively, all of which are bacterial gyrase inhibitors...
  83. ncbi Streptococcus pneumononiae gyrase ATPase: development and validation of an assay for inhibitor discovery and characterization
    J Richard Miller
    Department of Antibacterial Biology, Pfizer Global Research and Development, Ann Arbor, MI 48105, USA
    Anal Biochem 365:132-43. 2007
    ..Inhibition of the ATPase activity of DNA gyrase is the mechanism by which coumarin-class antibiotics such as novobiocin inhibit bacterial growth...
  84. ncbi Metabolic engineering of aminocoumarins: inactivation of the methyltransferase gene cloP and generation of new clorobiocin derivatives in a heterologous host
    Anja Freitag
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Chembiochem 6:1411-8. 2005
    ..Attachment at 4-OH resulted in the highest antibacterial activity. This is the first time that an aminocoumarin antibiotic acylated at 4-OH in noviose has been detected...
  85. pmc Rate of inversion of the Salmonella enterica shufflon regulates expression of invertible DNA
    Connie K P Tam
    Department of Biochemistry, Hong Kong University of Science and Technology, Clear Water Bay, Hong Kong, China
    Infect Immun 73:5568-77. 2005
    ..is influenced by the extent of DNA supercoiling, with increasing levels of expression of invertible genes as novobiocin inhibits DNA supercoiling and thus Rci action...
  86. ncbi Biosynthesis of clorobiocin: investigation of the transfer and methylation of the pyrrolyl-2-carboxyl moiety
    Christine Anderle
    Pharmazeutische Biologie, Pharmazeutisches Institut, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Arch Microbiol 187:227-37. 2007
    ..A mechanism for the methylation/acyl transfer process in the late steps of clorobiocin biosynthesis, involving CloN1, CloN2, CloN5, CloN6 and CloN7 is suggested...
  87. pmc Antimicrobial and DNA gyrase-inhibitory activities of novel clorobiocin derivatives produced by mutasynthesis
    Ute Galm
    Pharmazeutische Biologie, Pharmazeutisches Institut, D 72076 Tuebingen, Germany
    Antimicrob Agents Chemother 48:1307-12. 2004
    ..antibacterial activities towards clinically relevant gram-positive and gram-negative bacteria in comparison to novobiocin and clorobiocin. Clorobiocin was the most active compound both against E...
  88. pmc Antibiotic-sensitive TolC mutants and their suppressors
    Anne Marie Augustus
    Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona 85287, USA
    J Bacteriol 186:1851-60. 2004
    ..suppressor T140A, the overexpression of AcrAB diminished hypersensitivity towards only erythromycin and novobiocin, which are substrates of the TolC-AcrAB efflux pump, but not towards vancomycin, which is not a substrate of ..
  89. pmc Nucleotide sequence of the Staphylococcus aureus gyrB-gyrA locus encoding the DNA gyrase A and B proteins
    E E Margerrison
    Department of Cellular and Molecular Sciences, St George s Hospital Medical School, Cranmer Terrace, London, United Kingdom
    J Bacteriol 174:1596-603. 1992
    ..subtilis. These results are discussed in regard to the mechanism of DNA gyrase and its role as a target for the 4-quinolones and other antistaphylococcal agents...
  90. ncbi Molecular cloning and sequence analysis of the clorobiocin biosynthetic gene cluster: new insights into the biosynthesis of aminocoumarin antibiotics
    Florence Pojer
    Eberhard Karls Universitat Tubingen, Pharmazeutische Biologie, Auf der Morgenstelle 8, D 72076 Tubingen, Germany
    Microbiology 148:3901-11. 2002
    ..976 with two heterologous probes from the novobiocin biosynthetic gene cluster...
  91. pmc Alternative splicing controls the mechanisms of FAK autophosphorylation
    Madeleine Toutant
    INSERM UPMC U536, Institut du Fer a Moulin, 75005 Paris, France
    Mol Cell Biol 22:7731-43. 2002
    ..Our results clarify the mechanisms of FAK activation and show how alternative splicing can dramatically alter the mechanism of autophosphorylation of a protein kinase...
  92. ncbi Site-directed mutagenesis studies of the amino acid residue at position 412 of Escherichia coli TolC which is required for the activity
    Hiroyasu Yamanaka
    Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro, Tokushima, Tokushima, 770 8514, Japan
    Microb Pathog 33:81-9. 2002
    ..Further mutational research on the residue suggested that TolC required a nonpolar amino acid residue at position 412 to express its activity...
  93. ncbi novE and novG act as positive regulators of novobiocin biosynthesis
    Volker Dangel
    Pharmaceutical Biology, Pharmaceutical Institute, Eberhard Karls Universitat Tubingen, Auf der Morgenstelle 8, 72076 Tubingen, Germany
    Arch Microbiol 190:509-19. 2008
    The biosynthetic gene cluster of the aminocoumarin antibiotic novobiocin contains two putative regulatory genes, i.e., novE and novG...
  94. ncbi DNA gyrase interaction with coumarin-based inhibitors: the role of the hydroxybenzoate isopentenyl moiety and the 5'-methyl group of the noviose
    Daniel Lafitte
    UMR CNRS 6032, UFR de Pharmacie, 27 Bd Jean Moulin, 13385 Marseille Cedex 5, France
    Biochemistry 41:7217-23. 2002
    ..We provide the first experimental evidence that clorobiocin binds gyrase with a stronger affinity than novobiocin. We also demonstrate the crucial role of both the hydroxybenzoate isopentenyl moiety and the 5'-alkyl group on ..
  95. ncbi The Hsp90 inhibitor radicicol interacts with the ATP-binding pocket of bacterial sensor kinase PhoQ
    Michael T Guarnieri
    Department of Biochemistry and Molecular Genetics, University of Colorado Denver Anschutz Medical Campus, Aurora, CO 80045, USA
    J Mol Biol 379:82-93. 2008
    ..Our results suggest that GHL inhibitors may be useful lead compounds for developing sensor kinase inhibitors...
  96. pmc Promoter protection by a transcription factor acting as a local topological homeostat
    Mark Rochman
    Max Planck Institute for Terrestrial Microbiology, Karl von Frisch Strasse, D 35043 Marburg, Germany
    EMBO Rep 3:355-60. 2002
    ..We infer that FIS maintains stable RNA transcription by stabilizing local writhe in the UAS. These results suggest a novel mechanism of transcriptional regulation by a transcription factor acting as a local topological homeostat...
  97. ncbi A scintillation proximity assay amenable for screening and characterization of DNA gyrase B subunit inhibitors
    Monica Gevi
    GlaxoSmithKline Medicines Research Centre, Via Fleming, 4, Verona 37135, Italy
    Anal Biochem 300:34-9. 2002
    ..10 nM was found. Displacement studies gave 50% inhibitory concentrations (IC(50)) of 42, 64, and 11 nM for novobiocin, dihydronovobiocin, and the cyclothialidine analogue GR122222X, respectively, consistent with previous findings...
  98. ncbi Characterization of a putative RND-type efflux system in Agrobacterium tumefaciens
    W T Peng
    Department of Microbiology, University of Washington, Seattle, WA 98195 7242, USA
    Gene 270:245-52. 2001
    ..The possible role of the putative efflux pump coded by the ame genes is discussed...
  99. pmc The nature of inhibition of DNA gyrase by the coumarins and the cyclothialidines revealed by X-ray crystallography
    R J Lewis
    Laboratory of Molecular Biophysics, University of Oxford, UK
    EMBO J 15:1412-20. 1996
    ..in complexes with two different inhibitors of the ATPase activity of DNA gyrase, namely the coumarin antibiotic, novobiocin, and GR122222X, a member of the cyclothialidine family...
  100. pmc Temperature-sensitive suppressor mutations of the Escherichia coli DNA gyrase B protein
    S J Blance
    Department of Biochemistry, University of Leicester, United Kingdom
    Protein Sci 9:1035-7. 2000
    ..The properties of proteins bearing these mutations have been characterized, and a mechanism of suppression is proposed based upon structural considerations...
  101. pmc A microarray-based antibiotic screen identifies a regulatory role for supercoiling in the osmotic stress response of Escherichia coli
    Kevin J Cheung
    Department of Genetics, Harvard Medical School, Boston, Massachusetts 02115, USA
    Genome Res 13:206-15. 2003
    ..by expression profiling under conditions of high salt, in conjunction with the microbial antibiotics novobiocin, pefloxacin, and chloramphenicol...

Research Grants16

  1. Chaperone therapeutics for the treatment of DPN
    Rick T Dobrowsky; Fiscal Year: 2013
    ..The lead compound for these inhibitors, KU- 32, is based upon novobiocin. KU-32 protects against hyperglycemia-induced death of sensory neurons and can attenuate several physiologic ..
  2. Structure of the multidrug efflux protein AcrA
    Partho Ghosh; Fiscal Year: 2006
    ..The most thoroughly characterized RND system is the E. coli AcrAB-TolC system, which promotes efflux of novobiocin, erythromycin, fusidic acid, tetracycline, and chloramphenicol among others...
  3. REGULATION OF MACROPHAGE DEPENDENT ANGIOGENIC ACTIVITY
    SAMUEL LEIBOVICH; Fiscal Year: 2002
    ..b>Novobiocin, Vitamin-K1, and Vitamin-K3 will be tested...
  4. MODULATION OF HIGH-DOSE ALKYLATOR EFFICACY BY NOVOBIOCIN
    Michael Kennedy; Fiscal Year: 1992
    ..The coumeramycin antibiotic novobiocin can potentiate the cytotoxic effects of a number of alkylating agents against cancer cell lines in-vitro by ..
  5. ROLE OF DNA REPAIR IN CISPLATIN RESISTANCE
    J Eder; Fiscal Year: 1993
    ..Resistance to cDDP in human cancer cells is multifactorial, and enhanced DNA repair may be one such mechanism. Novobiocin (NB), an inhibitor of DNA repair and of DNA topoisomerase II (top II) (not necessarily by the same mechanism), ..
  6. GENOMIC DOMAINS AND TOPOISOMERASES IN GENE REGULATION
    HAROLD MARTINSON; Fiscal Year: 1990
    ..Gamma irradiation of chick red blood cells or inhibition of the topoisomerase II using novobiocin, both lead to reversal of DNase I sensitivity as assayed by dot blot hybridization to globin gene probes...
  7. MULTITARGET DRUGS: VERIFICATION-OF-PRINCIPLE STUDIES
    Alexander Varshavsky; Fiscal Year: 2001
    ..coli TetR repressor). 3) Bipartite, IC-type compounds containing the novobiocin (nov) moiety and either the methotrexate (mtx) or the trimetrexate (tm) moiety will be synthesized and tested ..
  8. Ciprofloxacin resistance and compensatory Mutations.
    Julian Adams; Fiscal Year: 2004
    ..anthracis. The study will also be extended to include E. coli and two other antibiotics, novobiocin and ceftazidime...
  9. DEVELOPMENT OF NEW LIPID A BINDING AGENTS
    Paul Savage; Fiscal Year: 2002
    ..Association of PMB and the new LA-binders with LA and LA derivatives will be compared using microtitration calorimetry. ..
  10. Biofilm growth and detachment of an oral pathogen
    Jeffrey Kaplan; Fiscal Year: 2007
    ..abstract_text> ..
  11. Hunter Killer Peptides: Membrane Interactions and Receptor Binding
    Leigh Plesniak; Fiscal Year: 2007
    ..A second HKP that kills white fat tissue reduces fatty deposits and has a positive impact on glucose metabolism, reducing symptoms of diabetes. [unreadable] [unreadable] [unreadable]..
  12. Amino acid prototrophy as a positive selective marker in Francisella
    James Bina; Fiscal Year: 2008
    ..tularensis strains. [unreadable] [unreadable] [unreadable]..
  13. Basal Ig Signaling and Receptor Editing
    Michael Farrar; Fiscal Year: 2009
    ..abstract_text> ..
  14. GENETIC ANALYSIS OF CHLAMYDIAL VIRULENCE
    CATHERINE O CONNELL; Fiscal Year: 2002
    ..In addition, we anticipate identifying at least one MoPn gene that contributes to the virulence of this strain. ..