dna gyrase

Summary

Summary: A bacterial DNA topoisomerase II that catalyzes ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. Gyrase binds to DNA as a heterotetramer consisting two A and two B subunits. In the presence of ATP, gyrase is able to convert relaxed circular DNA duplex into a superhelix. In the absence of ATP, supercoiled DNA is relaxed by DNA gyrase.

Top Publications

  1. pmc Exploiting bacterial DNA gyrase as a drug target: current state and perspectives
    Frédéric Collin
    Department Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK
    Appl Microbiol Biotechnol 92:479-97. 2011
  2. doi Type IIA topoisomerase inhibition by a new class of antibacterial agents
    Benjamin D Bax
    Molecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK
    Nature 466:935-40. 2010
  3. pmc A systematic review of gyrase mutations associated with fluoroquinolone-resistant Mycobacterium tuberculosis and a proposed gyrase numbering system
    Fernanda Maruri
    Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
    J Antimicrob Chemother 67:819-31. 2012
  4. pmc Sequence analyses of just four genes to detect extensively drug-resistant Mycobacterium tuberculosis strains in multidrug-resistant tuberculosis patients undergoing treatment
    Silke Feuerriegel
    Research Center Borstel, National Reference Center for Mycobacteria, Parkallee 18, 23845 Borstel, Germany
    Antimicrob Agents Chemother 53:3353-6. 2009
  5. pmc Mechanisms for defining supercoiling set point of DNA gyrase orthologs: II. The shape of the GyrA subunit C-terminal domain (CTD) is not a sole determinant for controlling supercoiling efficiency
    Elsa M Tretter
    Division of Biochemistry, Biophysics, and Structural Biology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA
    J Biol Chem 287:18645-54. 2012
  6. pmc Functional characterisation of mycobacterial DNA gyrase: an efficient decatenase
    U H Manjunatha
    Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560 012, India
    Nucleic Acids Res 30:2144-53. 2002
  7. ncbi Topological insulators inhibit diffusion of transcription-induced positive supercoils in the chromosome of Escherichia coli
    Laurent Moulin
    Centre de Génétique Moléculaire du CNRS, Bat 26, 1 Avenue de la Terrasse, F 91198 Gif sur Yvette, France and Centre de Biophysique Moléculaire du CNRS, Avenue Ch Sadron, F 45071 Orléans, France
    Mol Microbiol 55:601-10. 2005
  8. pmc Mechanism of plasmid-mediated quinolone resistance
    John H Tran
    Infectious Disease Department, Lahey Clinic, Burlington, MA 01805, USA
    Proc Natl Acad Sci U S A 99:5638-42. 2002
  9. pmc Fluoroquinolone resistance in Mycobacterium tuberculosis and mutations in gyrA and gyrB
    Andrea von Groll
    Mycobacteriology Unit, Institute of Tropical Medicine, Antwerp, Belgium
    Antimicrob Agents Chemother 53:4498-500. 2009
  10. ncbi First functional characterization of a singly expressed bacterial type II topoisomerase: the enzyme from Mycobacterium tuberculosis
    Alexandra Aubry
    Laboratoire de Bacteriologie, Faculté de Médecine Pitié Salpêtrière, EA1541, Universite Paris 6, France
    Biochem Biophys Res Commun 348:158-65. 2006

Research Grants

Detail Information

Publications327 found, 100 shown here

  1. pmc Exploiting bacterial DNA gyrase as a drug target: current state and perspectives
    Frédéric Collin
    Department Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich, NR4 7UH, UK
    Appl Microbiol Biotechnol 92:479-97. 2011
    b>DNA gyrase is a type II topoisomerase that can introduce negative supercoils into DNA at the expense of ATP hydrolysis. It is essential in all bacteria but absent from higher eukaryotes, making it an attractive target for antibacterials...
  2. doi Type IIA topoisomerase inhibition by a new class of antibacterial agents
    Benjamin D Bax
    Molecular Discovery Research, GlaxoSmithKline, Medicines Research Centre, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK
    Nature 466:935-40. 2010
    ..structure of a potent, new class, broad-spectrum antibacterial agent in complex with Staphylococcus aureus DNA gyrase and DNA, showing a new mode of inhibition that circumvents fluoroquinolone resistance in this clinically ..
  3. pmc A systematic review of gyrase mutations associated with fluoroquinolone-resistant Mycobacterium tuberculosis and a proposed gyrase numbering system
    Fernanda Maruri
    Division of Infectious Diseases, Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA
    J Antimicrob Chemother 67:819-31. 2012
    ..A review of mutations in DNA gyrase, the fluoroquinolone target, is needed to improve the molecular detection of resistance...
  4. pmc Sequence analyses of just four genes to detect extensively drug-resistant Mycobacterium tuberculosis strains in multidrug-resistant tuberculosis patients undergoing treatment
    Silke Feuerriegel
    Research Center Borstel, National Reference Center for Mycobacteria, Parkallee 18, 23845 Borstel, Germany
    Antimicrob Agents Chemother 53:3353-6. 2009
    ..The mechanisms that confer amikacin resistance in this setting remain unclear...
  5. pmc Mechanisms for defining supercoiling set point of DNA gyrase orthologs: II. The shape of the GyrA subunit C-terminal domain (CTD) is not a sole determinant for controlling supercoiling efficiency
    Elsa M Tretter
    Division of Biochemistry, Biophysics, and Structural Biology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA
    J Biol Chem 287:18645-54. 2012
    ..Our observations demonstrate that gyrase has been modified in multiple ways throughout evolution to fine-tune its specific catalytic properties...
  6. pmc Functional characterisation of mycobacterial DNA gyrase: an efficient decatenase
    U H Manjunatha
    Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560 012, India
    Nucleic Acids Res 30:2144-53. 2002
    A rapid single step immunoaffinity purification procedure is described for Mycobacterium smegmatis DNA gyrase. The mycobacterial enzyme is a 340 kDa heterotetrameric protein comprising two subunits each of GyrA and GyrB, exhibiting subtle ..
  7. ncbi Topological insulators inhibit diffusion of transcription-induced positive supercoils in the chromosome of Escherichia coli
    Laurent Moulin
    Centre de Génétique Moléculaire du CNRS, Bat 26, 1 Avenue de la Terrasse, F 91198 Gif sur Yvette, France and Centre de Biophysique Moléculaire du CNRS, Avenue Ch Sadron, F 45071 Orléans, France
    Mol Microbiol 55:601-10. 2005
    ..e. behave as topological insulators. All the elements tested correspond to DNA gyrase catalytic targets...
  8. pmc Mechanism of plasmid-mediated quinolone resistance
    John H Tran
    Infectious Disease Department, Lahey Clinic, Burlington, MA 01805, USA
    Proc Natl Acad Sci U S A 99:5638-42. 2002
    Quinolones are potent antibacterial agents that specifically target bacterial DNA gyrase and topoisomerase IV. Widespread use of these agents has contributed to the rise of bacterial quinolone resistance...
  9. pmc Fluoroquinolone resistance in Mycobacterium tuberculosis and mutations in gyrA and gyrB
    Andrea von Groll
    Mycobacteriology Unit, Institute of Tropical Medicine, Antwerp, Belgium
    Antimicrob Agents Chemother 53:4498-500. 2009
    ..Forty strains shared the same resistance results for the three fluoroquinolones. However, one strain, with an Asn-533 --> Thr mutation in gyrB, was susceptible to ofloxacin but resistant to moxifloxacin and gatifloxacin...
  10. ncbi First functional characterization of a singly expressed bacterial type II topoisomerase: the enzyme from Mycobacterium tuberculosis
    Alexandra Aubry
    Laboratoire de Bacteriologie, Faculté de Médecine Pitié Salpêtrière, EA1541, Universite Paris 6, France
    Biochem Biophys Res Commun 348:158-65. 2006
    ..encodes a single type II topoisomerase contrary to common bacteria harboring two type II topoisomerases (DNA gyrase and topoisomerase IV). Functions of the M...
  11. doi Prevalence of primary fluoroquinolone resistance among clinical isolates of Helicobacter pylori at a University Hospital in Southern Taiwan
    Kuei Hsiang Hung
    Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan
    Helicobacter 14:61-5. 2009
    ..pylori to fluoroquinolones in Taiwan has not yet been reported. In this study, we aimed to investigate the susceptibility to antibiotics commonly used in eradication schedules and fluoroquinolones in H. pylori...
  12. pmc The ancestral role of ATP hydrolysis in type II topoisomerases: prevention of DNA double-strand breaks
    Andrew D Bates
    Institute of Integrative Biology, University of Liverpool, Biosciences Building, Crown Street, Liverpool L69 7ZB, UK
    Nucleic Acids Res 39:6327-39. 2011
    ..All type II topos hydrolyse ATP during their reactions; however, only DNA gyrase is able to harness the free energy of hydrolysis to drive DNA supercoiling, an energetically unfavourable ..
  13. pmc DNA gyrase inhibition assays are necessary to demonstrate fluoroquinolone resistance secondary to gyrB mutations in Mycobacterium tuberculosis
    Alix Pantel
    UPMC Universite Paris 06, ER5, EA 1541, Laboratoire de Bacteriologie Hygiene, F 75005 Paris, France
    Antimicrob Agents Chemother 55:4524-9. 2011
    The main mechanism of fluoroquinolone (FQ) resistance in Mycobacterium tuberculosis is mutation in DNA gyrase (GyrA(2)GyrB(2)), especially in gyrA...
  14. pmc Impact of the E540V amino acid substitution in GyrB of Mycobacterium tuberculosis on quinolone resistance
    Hyun Kim
    Department of Global Epidemiology, Hokkaido University Research Center for Zoonosis Control, Sapporo 001 0020, Japan
    Antimicrob Agents Chemother 55:3661-7. 2011
    ..have generally been found within the quinolone resistance-determining regions (QRDRs) in the A subunit of DNA gyrase (GyrA) rather than the B subunit of DNA gyrase (GyrB)...
  15. pmc Rapid detection of fluoroquinolone-resistant and heteroresistant Mycobacterium tuberculosis by use of sloppy molecular beacons and dual melting-temperature codes in a real-time PCR assay
    Soumitesh Chakravorty
    Division of Infectious Disease, Department of Medicine and the Ruy V Lourenço Center for the Study of Emerging and Reemerging Pathogens, New Jersey Medical School, Newark, NJ 07103, USA
    J Clin Microbiol 49:932-40. 2011
    ..This SMB T(m) shift assay will be a valuable molecular tool to rapidly detect FQ resistance and to detect the emergence of FQ heteroresistance in clinical samples from tuberculosis patients...
  16. pmc A domain insertion in Escherichia coli GyrB adopts a novel fold that plays a critical role in gyrase function
    Allyn J Schoeffler
    Department of Molecular and Cell Biology, California Institute for Quantitative Biosciences, University of California, Berkeley and Fluidigm Corporation, South San Francisco, CA 94080, USA
    Nucleic Acids Res 38:7830-44. 2010
    ..Our data indicate that the insert has two functions, acting as a steric buttress to pre-configure the primary DNA-binding site, and serving as a relay that may help coordinate communication between different functional domains...
  17. ncbi Mechanisms of quinolone resistance in Escherichia coli and Salmonella: recent developments
    Katie L Hopkins
    Antimicrobial Resistance and Molecular Epidemiology Unit, Laboratory of Enteric Pathogens, Health Protection Agency Centre for Infections, 61 Colindale Avenue, London NW9 5HT, UK
    Int J Antimicrob Agents 25:358-73. 2005
    ....
  18. pmc Emergence of ofloxacin resistance in Mycobacterium tuberculosis clinical isolates from China as determined by gyrA mutation analysis using denaturing high-pressure liquid chromatography and DNA sequencing
    Ruiru Shi
    Mycobacterial Reference Center, The Research Institute of Tuberculosis, 3 1 24 Matsuyama, Kiyose, Tokyo 204 0022, Japan
    J Clin Microbiol 44:4566-8. 2006
    ..This is the first report to describe denaturing high-pressure liquid chromatography analysis of mutations in gyrA of M. tuberculosis in a large number of clinical isolates...
  19. ncbi Fluoroquinolone resistance in Mycobacterium tuberculosis isolates: associated genetic mutations and relationship to antimicrobial exposure
    Jann Yuan Wang
    Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan
    J Antimicrob Chemother 59:860-5. 2007
    ..We assessed the fluoroquinolone (FQ) susceptibility of clinical isolates of Mycobacterium tuberculosis in an endemic area. The genetic mutations responsible for FQ resistance were also evaluated...
  20. pmc Quinolone resistance in Escherichia coli from Accra, Ghana
    Sreela S Namboodiri
    Department of Biology, Haverford College, Haverford, PA 19041, USA
    BMC Microbiol 11:44. 2011
    ..We sought to determine the prevalence of resistance to broad-spectrum antimicrobials with particular focus on the quinolones, which have recently been introduced in parts of Africa, including Ghana...
  21. pmc Structural insights into the quinolone resistance mechanism of Mycobacterium tuberculosis DNA gyrase
    Jérémie Piton
    Unité de Dynamique Structurale des Macromolécules, Departement de Biologie Structurale et Chimie, Institut Pasteur, Paris, France
    PLoS ONE 5:e12245. 2010
    Mycobacterium tuberculosis DNA gyrase, an indispensable nanomachine involved in the regulation of DNA topology, is the only type II topoisomerase present in this organism and is hence the sole target for quinolone action, a crucial drug ..
  22. ncbi Reduction of the fitness burden of quinolone resistance in Pseudomonas aeruginosa
    Elisabeth Kugelberg
    Swedish Institute for Infectious Disease Control, Department of Bacteriology, S 171 82 Solna, Sweden
    J Antimicrob Chemother 55:22-30. 2005
    ..opportunistic pathogen Pseudomonas aeruginosa is commonly caused by mutations that alter the target molecules DNA gyrase/topoisomerase IV, or cause activation of various efflux systems...
  23. pmc Crystal structure of DNA gyrase B' domain sheds lights on the mechanism for T-segment navigation
    Guangsen Fu
    National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, People s Republic of China
    Nucleic Acids Res 37:5908-16. 2009
    b>DNA gyrase is an indispensible marvelous molecular machine in manipulating the DNA topology for the prokaryotes...
  24. pmc Novel gyrase mutations in quinolone-resistant and -hypersusceptible clinical isolates of Mycobacterium tuberculosis: functional analysis of mutant enzymes
    Alexandra Aubry
    Molecular Genetics Group, Molecular and Metabolic Signaling Centre, Division of Basic Medical Scinces, St George s, University of London, United Kingdom
    Antimicrob Agents Chemother 50:104-12. 2006
    Mutations in the DNA gyrase GyrA2GyrB2 complex are associated with resistance to quinolones in Mycobacterium tuberculosis...
  25. ncbi Nucleotide binding to DNA gyrase causes loss of DNA wrap
    Jonathan G Heddle
    Department of Biological Chemistry, John Innes Centre, Colney, Norwich NR4 7UH, UK
    J Mol Biol 337:597-610. 2004
    b>DNA gyrase negatively supercoils DNA in a reaction coupled to the binding and hydrolysis of ATP. Limited supercoiling can be achieved in the presence of the non-hydrolysable ATP analogue, 5'-adenylyl beta,gamma-imidodiphosphate (ADPNP)...
  26. ncbi Dissection of the nucleotide cycle of B. subtilis DNA gyrase and its modulation by DNA
    Thomas Göttler
    Division of Biophysical Chemistry, Biozentrum, University of Basel, CH 4056 Basel, Switzerland
    J Mol Biol 367:1392-404. 2007
    ..While all type II DNA topoisomerases relax supercoiled DNA, DNA gyrase is the only enyzme that introduces negative supercoils into DNA at the expense of ATP hydrolysis...
  27. ncbi Effect of different classes of inhibitors on DNA gyrase from Mycobacterium smegmatis
    M Chatterji
    Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore, India 560012
    J Antimicrob Chemother 48:479-85. 2001
    Quinolones, coumarins, cyclothialidines, CcdB and microcin B17 inhibit DNA gyrase. Information regarding these various inhibitors comes from studies performed with the enzyme from Escherichia coli, and subsequent analyses have also ..
  28. pmc Relationship between mutations in the gyrA gene and quinolone resistance in clinical isolates of Corynebacterium striatum and Corynebacterium amycolatum
    Josep M Sierra
    Department of Microbiology, School of Medicine, Hospital Clinic, IDIBAPS, University of Barcelona, Barcelona, Spain
    Antimicrob Agents Chemother 49:1714-9. 2005
    ..amycolatum. Moreover, a PCR-RFLP-NcoI of the gyrA gene was developed to distinguish between C. amycolatum and C. striatum species...
  29. doi Population-based investigation of fluoroquinolones resistant tuberculosis in rural eastern China
    Yi Hu
    Department of Epidemiology, School of Public Health, Fudan University, 138 Yi Xue Yuan Rd, Shanghai 200032, China
    Tuberculosis (Edinb) 91:238-43. 2011
    ..The relatively low level of clustering among FQ-resistant strains suggests most are acquired de novo, likely due to widespread FQ use...
  30. pmc In vivo selection of Campylobacter isolates with high levels of fluoroquinolone resistance associated with gyrA mutations and the function of the CmeABC efflux pump
    Naidan Luo
    Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Department of Veterinary Preventive Medicine, The Ohio State University, Wooster, Ohio 44691, USA
    Antimicrob Agents Chemother 47:390-4. 2003
    ..These results reveal that Campylobacter is hypermutable in vivo under the selection pressure of FQ and highlight the need for the prudent use of FQ antibiotics...
  31. ncbi Selection and characterization of fluoroquinolone-resistant mutants of Campylobacter jejuni using enrofloxacin
    Sophie Payot
    UR86 de Pathologie Aviaire et Parasitologie, Institut National de la Recherche Agronomique, 37380 Nouzilly, France
    Microb Drug Resist 8:335-43. 2002
    ..jejuni isolates. Results obtained during ciprofloxacin accumulation studies confirmed that efflux probably plays a minor role in fluoroquinolone resistance of C. jejuni...
  32. ncbi Mechanisms of quinolone action and microbial response
    Peter M Hawkey
    Public Health Laboratory, Heartlands Hospital, Bordesley Green East, Birmingham B5 9SS, UK
    J Antimicrob Chemother 51:29-35. 2003
    ..However, it is conceivable that in the future, horizontal gene transfer may become a more important means of conferring resistance to fluoroquinolones...
  33. pmc Gyrase mutations in laboratory-selected, fluoroquinolone-resistant mutants of Mycobacterium tuberculosis H37Ra
    T Kocagoz
    Department of Medicine, University of California, San Francisco 94110, USA
    Antimicrob Agents Chemother 40:1768-74. 1996
    ..Because sparfloxacin is more active in vitro and selection of resistance appears to be less likely to occur, it may have important advantage over ofloxacin or ciprofloxacin for the treatment of tuberculosis...
  34. doi Mutation characterization of gyrA and gyrB genes in levofloxacin-resistant Mycobacterium tuberculosis clinical isolates from Guangdong Province in China
    Xiaomao Yin
    Institute for Pulmonary Disease, Guangzhou Chest Hospital, Yuexiu District, Guangzhou City, Guangdong Province, China
    J Infect 61:150-4. 2010
    ..The aim of this study was to observe the molecular characterization of gyrA and gyrB genes in FQ-resistant MTB clinical isolates from Guangdong Province in China...
  35. pmc Prevalence of plasmid-mediated quinolone resistance determinants over a 9-year period
    Hong Bin Kim
    Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Republic of Korea
    Antimicrob Agents Chemother 53:639-45. 2009
    ....
  36. ncbi Characterization of pyrazinamide and ofloxacin resistance among drug resistant Mycobacterium tuberculosis isolates from Singapore
    Ann S G Lee
    Department of Clinical Research, Singapore General Hospital, Singapore
    Int J Infect Dis 6:48-51. 2002
    ..To evaluate rapid molecular approaches for the detection of pyrazinamide (PZA) and ofloxacin resistance, by screening 100 known drug-resistant Mycobacterium tuberculosis isolates...
  37. doi Novel dual-targeting benzimidazole urea inhibitors of DNA gyrase and topoisomerase IV possessing potent antibacterial activity: intelligent design and evolution through the judicious use of structure-guided design and structure-activity relationships
    Paul S Charifson
    Vertex Pharmaceuticals Incorporated, 130 Waverly Street, Cambridge, Massachusetts 02139, USA
    J Med Chem 51:5243-63. 2008
    ..Bacterial DNA gyrase and topoisomerase IV are well-characterized clinically validated targets of the fluoroquinolone antibiotics ..
  38. pmc Enhancement of fluoroquinolone activity by C-8 halogen and methoxy moieties: action against a gyrase resistance mutant of Mycobacterium smegmatis and a gyrase-topoisomerase IV double mutant of Staphylococcus aureus
    T Lu
    Public Health Research Institute, 455 First Ave, New York, NY 10016, USA
    Antimicrob Agents Chemother 45:2703-9. 2001
    ....
  39. doi Antimicrobial effects of H4-(86-100), histogranin and related compounds--possible involvement of DNA gyrase
    Simon Lemaire
    Department of Molecular and Cellular Medicine, University of Ottawa, Canada
    FEBS J 275:5286-97. 2008
    ..the antimicrobial activities of H4-(86-100), HNr and compound 3, like those of quinolone antibiotics acting as DNA gyrase poisons, are potentiated by ATP (1 mM) and coumermycin A1 (a DNA gyrase-linked ATPase inhibitor) and blocked by ..
  40. pmc Guiding strand passage: DNA-induced movement of the gyrase C-terminal domains defines an early step in the supercoiling cycle
    Martin A Lanz
    University of Basel, Biozentrum, Biophysical Chemistry, Klingelbergstrasse 70, CH 4056 Basel, Switzerland
    Nucleic Acids Res 39:9681-94. 2011
    b>DNA gyrase catalyzes ATP-dependent negative supercoiling of DNA in a strand passage mechanism...
  41. pmc The role of Ca²⁺ in the activity of Mycobacterium tuberculosis DNA gyrase
    Shantanu Karkare
    Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Norwich NR4 7UH, UK
    Nucleic Acids Res 40:9774-87. 2012
    b>DNA gyrase is the only type II topoisomerase in Mycobacterium tuberculosis and needs to catalyse DNA supercoiling, relaxation and decatenation reactions in order to fulfil the functions normally carried out by gyrase and DNA topoisomerase ..
  42. pmc Distribution of spontaneous gyrA mutations in 97 fluoroquinolone-resistant Helicobacter pylori isolates collected in France
    Magali Garcia
    EA 4331 LITEC, Universite de Poitiers, CHU de Poitiers, Laboratoire de Bacteriologie Hygiene, Poitiers, France
    Antimicrob Agents Chemother 56:550-1. 2012
    ....
  43. pmc Are all the DNA gyrase mutations found in Mycobacterium leprae clinical strains involved in resistance to fluoroquinolones?
    Stephanie Matrat
    Universite Pierre et Marie Curie Paris 6, Paris, France
    Antimicrob Agents Chemother 52:745-7. 2008
    ..We demonstrated that the gyrA mutations leading to G89C or A91V confer fluoroquinolone resistance whereas the gyrB mutation leading to D205N does not...
  44. pmc Single and double mutations in gyrA but not in gyrB are associated with low- and high-level fluoroquinolone resistance in Helicobacter pylori
    Jacques Tankovic
    Laboratoire de Bacteriologie, Centre Hospitalo Universitaire Saint Antoine, Assistance Publique Hopitaux de Paris, Universite Paris VI, Paris, France
    Antimicrob Agents Chemother 47:3942-4. 2003
    ..Clinafloxacin and garenoxacin were the most active fluoroquinolones against these mutants. Occurrence of a second gyrA mutation was associated with high MICs of all fluoroquinolones tested...
  45. doi A high-throughput assay for DNA topoisomerases and other enzymes, based on DNA triplex formation
    Matthew R Burrell
    Department of Biological Chemistry, John Innes Centre, Norwich, UK
    Methods Mol Biol 613:257-66. 2010
    ..The assay is performed in microtitre plates and can be adapted to high-throughput screening of libraries of potential inhibitors of topoisomerases including bacterial DNA gyrase.
  46. pmc Molecular characterization of fluoroquinolone resistance in Mycobacterium tuberculosis: functional analysis of gyrA mutation at position 74
    Ricky W T Lau
    Department of Microbiology, Queen Mary Hospital, University of Hong Kong, Hong Kong, China
    Antimicrob Agents Chemother 55:608-14. 2011
    ..A number of gyrA mutations (Glu21Gln, Ser95Thr, and Gly668Asp) were also characterized to be natural polymorphisms not associated with fluoroquinolone resistance...
  47. doi Molecular mechanisms of antibiotic resistance
    Gerard D Wright
    M G DeGroote Institute for Infectious Disease Research, McMaster University, 1200 Main St W, Hamilton, ON, Canada
    Chem Commun (Camb) 47:4055-61. 2011
    ..Understanding the chemical rationale and underpinnings of resistance is an essential component of our response to this clinical challenge...
  48. pmc Mechanisms for defining supercoiling set point of DNA gyrase orthologs: I. A nonconserved acidic C-terminal tail modulates Escherichia coli gyrase activity
    Elsa M Tretter
    Division of Biochemistry, Biophysics, and Structural Biology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA
    J Biol Chem 287:18636-44. 2012
    ..coli GyrA tail regulates DNA wrapping by the CTD to increase the coupling efficiency between ATP turnover and supercoiling, demonstrating that CTD functions can be fine-tuned to control gyrase activity in a highly sophisticated manner...
  49. pmc Extending the definition of the GyrB quinolone resistance-determining region in Mycobacterium tuberculosis DNA gyrase for assessing fluoroquinolone resistance in M. tuberculosis
    Alix Pantel
    UPMC Université Paris, Laboratoire de Bacteriologie Hygiene, Paris, France
    Antimicrob Agents Chemother 56:1990-6. 2012
    ..is amino acid substitution within the quinolone resistance-determining region (QRDR) of the GyrA subunit of DNA gyrase, the sole FQ target in M. tuberculosis...
  50. pmc Role of efflux pumps and topoisomerase mutations in fluoroquinolone resistance in Campylobacter jejuni and Campylobacter coli
    Beilei Ge
    Department of Nutrition and Food Science, 0112 Skinner Building, University of Maryland, College Park, MD 20742, USA
    Antimicrob Agents Chemother 49:3347-54. 2005
    Point mutations in the topoisomerase (DNA gyrase A) gene are known to be associated with fluoroquinolone resistance in Campylobacter...
  51. pmc Solution structures of DNA-bound gyrase
    Nicole M Baker
    Department of Molecular Biosciences, Northwestern University, Evanston, IL 60208, USA
    Nucleic Acids Res 39:755-66. 2011
    The DNA gyrase negative supercoiling mechanism involves the assembly of a large gyrase/DNA complex and conformational rearrangements coupled to ATP hydrolysis...
  52. pmc Genetic characterization of highly fluoroquinolone-resistant clinical Escherichia coli strains from China: role of acrR mutations
    H Wang
    Department of Clinical Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing 100730, People's Republic of China
    Antimicrob Agents Chemother 45:1515-21. 2001
    ..5- to 6-fold. This study shows that mutations in acrR are an additional genetic basis for fluoroquinolone resistance...
  53. ncbi Importance of the efflux pump systems in the resistance of Mycobacterium tuberculosis to fluoroquinolones and linezolid
    I Escribano
    Section of Microbiology, Hospital General Universitario de Elche, Universidad Miguel Hernandez, Elche, Spain
    Chemotherapy 53:397-401. 2007
    ..Our aim was to study the influence of efflux pump systems in the resistance of Mycobacterium tuberculosis to fluoroquinolones and linezolid...
  54. ncbi An open conformation of the Thermus thermophilus gyrase B ATP-binding domain
    Valerie Lamour
    Institut de Génétique et de Biologie Moléculaire, CNRS INSERM ULP, BP163, 1 rue Laurent Fries, 67404 Illkirch Cedex, France
    J Biol Chem 277:18947-53. 2002
    b>DNA gyrase forms an A(2)B(2) tetramer involved in DNA replication, repair, recombination, and transcription in which the B subunit catalyzes ATP hydrolysis...
  55. ncbi Multiple modes of Escherichia coli DNA gyrase activity revealed by force and torque
    Marcelo Nollmann
    Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA
    Nat Struct Mol Biol 14:264-71. 2007
    E. coli DNA gyrase uses the energy of ATP hydrolysis to introduce essential negative supercoils into the genome, thereby working against the mechanical stresses that accumulate in supercoiled DNA...
  56. pmc Simocyclinone D8, an inhibitor of DNA gyrase with a novel mode of action
    Ruth H Flatman
    Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Colney, Norwich NR4 7UH, UK
    Antimicrob Agents Chemother 49:1093-100. 2005
    We have characterized the interaction of a new class of antibiotics, simocyclinones, with bacterial DNA gyrase. Even though their structures include an aminocoumarin moiety, a key feature of novobiocin, coumermycin A(1), and clorobiocin, ..
  57. pmc YacG from Escherichia coli is a specific endogenous inhibitor of DNA gyrase
    Sugopa Sengupta
    Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560012, India
    Nucleic Acids Res 36:4310-6. 2008
    ..YacG was predicted to be a part of DNA gyrase interactome based on protein-protein interaction network...
  58. ncbi The antibiotic microcin B17 is a DNA gyrase poison: characterisation of the mode of inhibition
    J G Heddle
    Department of Biochemistry, University of Leicester, Leicester, LE1 7RH, UK
    J Mol Biol 307:1223-34. 2001
    Microcin B17 is a 3.1-kDa bactericidal peptide; the putative target of this antibiotic is DNA gyrase. Microcin B17 has no detectable effect on gyrase-catalysed DNA supercoiling or relaxation activities in vitro and is unable to stabilise ..
  59. pmc Molecular characterization of ofloxacin-resistant Mycobacterium tuberculosis strains from Russia
    Igor Mokrousov
    Laboratory of Molecular Microbiology, St Petersburg Pasteur Institute, 197101 St Petersburg, Russia
    Antimicrob Agents Chemother 52:2937-9. 2008
    ..tuberculosis...
  60. doi A crystal structure of the bifunctional antibiotic simocyclinone D8, bound to DNA gyrase
    Marcus J Edwards
    Department of Biological Chemistry, John Innes Centre, Colney, Norwich NR4 7UH, UK
    Science 326:1415-8. 2009
    Simocyclinones are bifunctional antibiotics that inhibit bacterial DNA gyrase by preventing DNA binding to the enzyme...
  61. pmc The DNA-gate of Bacillus subtilis gyrase is predominantly in the closed conformation during the DNA supercoiling reaction
    Airat Gubaev
    Biozentrum, Department of Biophysical Chemistry, University of Basel, Klingelbergstrasse 70, 4056 Basel, Switzerland
    Proc Natl Acad Sci U S A 106:13278-83. 2009
    ..During the relaxation and supercoiling reactions, gyrase with an open DNA-gate is not significantly populated, consistent with gate-opening as a very rare event that only occurs briefly to allow for strand passage...
  62. pmc Structural and biochemical analysis of the pentapeptide repeat protein EfsQnr, a potent DNA gyrase inhibitor
    Subray S Hegde
    Department of Biochemistry, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Antimicrob Agents Chemother 55:110-7. 2011
    ..EfsQnr was cloned with an N-terminal 6× His tag and purified to homogeneity. EfsQnr partially protected DNA gyrase from fluoroquinolone inhibition at concentrations as low as 20 nM...
  63. pmc The pentapeptide repeat proteins MfpAMt and QnrB4 exhibit opposite effects on DNA gyrase catalytic reactions and on the ternary gyrase-DNA-quinolone complex
    Audrey Merens
    Universite Paris, IFR, Bacteriologie, Creteil, France
    J Bacteriol 191:1587-94. 2009
    MfpA(Mt) and QnrB4 are two newly characterized pentapeptide repeat proteins (PRPs) that interact with DNA gyrase. The mfpA(Mt) gene is chromosome borne in Mycobacterium tuberculosis, while qnrB4 is plasmid borne in enterobacteria...
  64. pmc Should moxifloxacin be used for the treatment of extensively drug-resistant tuberculosis? An answer from a murine model
    Julien Poissy
    Laboratoire de Bacteriologie Hygiene, Faculte de Medecine, Pierre et Marie Curie Université Paris, 91 Boulevard de l Hopital, Paris Cedex 13, France
    Antimicrob Agents Chemother 54:4765-71. 2010
    ..The extent of Mycobacterium tuberculosis resistance to fluoroquinolones depends on the mutation in the DNA gyrase, the only target of fluoroquinolones. The MIC of moxifloxacin, the most active fluoroquinolone against M...
  65. doi DNA topoisomerases: harnessing and constraining energy to govern chromosome topology
    Allyn J Schoeffler
    Department of Molecular and Cell Biology, California Institute for Quantitative Biology, University of California Berkeley, Berkeley, CA, USA
    Q Rev Biophys 41:41-101. 2008
    ....
  66. pmc Measuring chromosome dynamics on different time scales using resolvases with varying half-lives
    Richard A Stein
    Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35294, USA
    Mol Microbiol 56:1049-61. 2005
    ..independent domains, each capable of constraining the plectonemic negative supercoil energy introduced by DNA gyrase. Different experimental approaches have estimated the number of domains to be between 40 and 150...
  67. ncbi Discovery and development of ATPase inhibitors of DNA gyrase as antibacterial agents
    Marko Oblak
    Lek Pharmaceuticals, D D, Drug Discovery, Ljubljana, Slovenia
    Curr Med Chem 14:2033-47. 2007
    b>DNA gyrase is an attractive and well established target for the development of antibacterial agents...
  68. pmc Evolutionary history of Salmonella typhi
    Philippe Roumagnac
    Max Planck Institut für Infektionsbiologie, Department of Molecular Biology, Chariteplatz 1, 10117 Berlin, Germany
    Science 314:1301-4. 2006
    ..Neutral evolution in Typhi appears to reflect the asymptomatic carrier state, and adaptive evolution depends on the rapid transmission of phenotypic changes through acute infections...
  69. doi Identification of Pseudomonas aeruginosa by a duplex real-time polymerase chain reaction assay targeting the ecfX and the gyrB genes
    Snehal N Anuj
    Department of Paediatrics and Child Health, University of Queensland, Brisbane 4029, Australia
    Diagn Microbiol Infect Dis 63:127-31. 2009
    ..aeruginosa identity where both the ecfX and gyrB PCR reactions are positive and may also reduce the potential for false negatives caused by sequence variation in primer or probe targets...
  70. ncbi Toxin-antitoxin modules as bacterial metabolic stress managers
    Lieven Buts
    Laboratorium voor Ultrastructuur, Vrije Universiteit Brussel, and Department of Molecular and Cellular Interactions, Vlaams Interuniversitair Instituut voor Biotechnologie, Pleinlaan 2, B 1050 Brussel, Belgium
    Trends Biochem Sci 30:672-9. 2005
    ..Under silent conditions the antidote inhibits the toxin and the toxin-antidote complex acts as a repressor for the TA operon, whereas under conditions of activation proteolytic degradation of the antidote outpaces its synthesis...
  71. pmc Prevalence of mutations within the quinolone resistance-determining region of gyrA, gyrB, parC, and parE and association with antibiotic resistance in quinolone-resistant Salmonella enterica
    Deborah J Eaves
    Antimicrobial Agents Research Group, Division of Immunity and Infection, University of Birmingham, Birmingham B15 2TT, United Kingdom
    Antimicrob Agents Chemother 48:4012-5. 2004
    ..Although it is counterintuitive, isolates with a mutation in both gyrA and parC were more susceptible to ciprofloxacin than were isolates with a mutation in gyrA alone...
  72. pmc Topoisomerase IV is a target of quinolones in Escherichia coli
    A B Khodursky
    Department of Molecular and Cell Biology, University of California, Berkeley 94720 3204, USA
    Proc Natl Acad Sci U S A 92:11801-5. 1995
    ..Our results imply that the quinolone binding pockets of gyrase and topo IV are similar and that substantial levels of drug resistance require mutations in both enzymes...
  73. pmc Enhanced in vivo fitness of fluoroquinolone-resistant Campylobacter jejuni in the absence of antibiotic selection pressure
    Naidan Luo
    Food Animal Health Research Program, Ohio Agricultural Research and Development Center, Ohio State University, Wooster, OH 44691, USA
    Proc Natl Acad Sci U S A 102:541-6. 2005
    ....
  74. ncbi Fluoroquinolone resistance in Campylobacter species from man and animals: detection of mutations in topoisomerase genes
    Laura J V Piddock
    Antimicrobial Agents Research Group, Department of Infection, The Medical School, University of Birmingham, Birmingham B15 2TT, UK
    J Antimicrob Chemother 51:19-26. 2003
    ..jejuni, which exhibited a valine at codon 86. Only 8/192 isolates had changes in gyrB; all were shown to relate to silent mutations in gyrB and presumably reflect natural polymorphisms in the gene...
  75. pmc Interplay in the selection of fluoroquinolone resistance and bacterial fitness
    Linda L Marcusson
    Microbiology Programme, Department of Cell and Molecular Biology, Biomedical Center, Uppsala University, Uppsala, Sweden
    PLoS Pathog 5:e1000541. 2009
    Fluoroquinolones are antibacterial drugs that inhibit DNA Gyrase and Topoisomerase IV. These essential enzymes facilitate chromosome replication and RNA transcription by regulating chromosome supercoiling...
  76. ncbi Trends in fluoroquinolone resistance of Mycobacterium tuberculosis complex in a Taiwanese medical centre: 1995-2003
    Tsi Shu Huang
    Section of Microbiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan, ROC
    J Antimicrob Chemother 56:1058-62. 2005
    ..We also sought to determine whether there might be clonal spread of fluoroquinolone resistance...
  77. ncbi Fluoroquinolone resistance detection in Mycobacterium tuberculosis with locked nucleic acid probe real-time PCR
    H R van Doorn
    Department of Medical Microbiology, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands
    Int J Tuberc Lung Dis 12:736-42. 2008
    ..Pham Ngoc Thach Hospital for Tuberculosis and Lung Diseases, Ho Chi Minh City, Vietnam...
  78. ncbi A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA
    Subray S Hegde
    Department of Biochemistry, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Science 308:1480-3. 2005
    ..This protein binds to DNA gyrase and inhibits its activity...
  79. ncbi Modular structure of the full-length DNA gyrase B subunit revealed by small-angle X-ray scattering
    Lionel Costenaro
    Department of Biological Chemistry, John Innes Centre, Norwich NR4 7UH, United Kingdom
    Structure 15:329-39. 2007
    b>DNA gyrase, the only topoisomerase able to introduce negative supercoils into DNA, is essential for bacterial transcription and replication; absent from humans, it is a successful target for antibacterials...
  80. ncbi Norfloxacin-induced DNA cleavage occurs at the dif resolvase locus in Escherichia coli and is the result of interaction with topoisomerase IV
    A Hojgaard
    Department of Pathology, University of Utah, Salt Lake City 84112, USA
    Mol Microbiol 33:1027-36. 1999
    ..Quinolone drugs, such as norfloxacin, inhibit the type 2 topoisomerases, DNA gyrase and topoisomerase IV, and can cleave DNA at sites where these enzymes interact with the chromosome...
  81. pmc A gyrase mutant with low activity disrupts supercoiling at the replication terminus
    Zhenhua Pang
    Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, 35294, USA
    J Bacteriol 187:7773-83. 2005
    ..b>DNA gyrase is an essential bacterial enzyme composed of two subunits, GyrA and GyrB...
  82. pmc Interplay of DNA supercoiling and catenation during the segregation of sister duplexes
    María Luisa Martínez-Robles
    Departamento de Biologia Celular y del Desarrollo, Centro de Investigaciones Biologicas CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain
    Nucleic Acids Res 37:5126-37. 2009
    ..simulations in order to better understand the relationship between the negative supercoiling of DNA generated by DNA gyrase and the DNA interlinking resulting from replication of circular DNA molecules...
  83. pmc Evaluation of a new line probe assay for rapid identification of gyrA mutations in Mycobacterium tuberculosis
    Federico Giannoni
    Dipartimento di Malattie Infettive, Parassitarie e Immunomediate, Istituto Superiore di Sanita, Viale Regina Elena 299, 00161 Rome, Italy
    Antimicrob Agents Chemother 49:2928-33. 2005
    ..5%) OFL-R strains. A nested-PCR protocol was also evaluated for the assay to amplify PCR products from M. tuberculosis-spiked sputa, with a good specificity and a sensitivity of 2 x 10(3) M. tuberculosis CFU per ml of sputum...
  84. 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
    Novobiocin is a member of the coumermycin family of antibiotics and is a well-established inhibitor of DNA gyrase. Recent studies have shown that novobiocin binds to a previously unrecognized ATP-binding site at the C-terminus of Hsp90 ..
  85. pmc In vivo and in vitro patterns of the activity of simocyclinone D8, an angucyclinone antibiotic from Streptomyces antibioticus
    Lisa M Oppegard
    Department of Pharmacology, University of Minnesota Medical School Twin Cities, 6 120 Jackson Hall, 321 Church Street SE, Minneapolis, MN 55455, USA
    Antimicrob Agents Chemother 53:2110-9. 2009
    ..Unlike quinolone treatment, however, SD8 treatment does not induce the SOS response. These results suggest that DNA gyrase is the target of SD8 in both gram-positive and gram-negative bacteria and that the lack of the antibacterial ..
  86. ncbi Cloning and primary structure of Staphylococcus aureus DNA topoisomerase IV: a primary target of fluoroquinolones
    L Ferrero
    Departement des Biotechnologies, Rhone Poulenc Rorer S A, Centre de Recherche de Vitry Alfortville, Vitry sur Seine, France
    Mol Microbiol 13:641-53. 1994
    A 4.6 kb Staphylococcus aureus DNA fragment containing DNA gyrase-like genes (grlA and grlB) was cloned and sequenced. The proteins GrlA and GrlB exhibit more than 30% identity with E...
  87. pmc Quinolone-resistant Haemophilus influenzae: determination of mutant selection window for ciprofloxacin, garenoxacin, levofloxacin, and moxifloxacin
    Xinying Li
    Public Health Research Institute, 225 Warren St, Newark, NJ 07103, USA
    Antimicrob Agents Chemother 48:4460-2. 2004
    ..Successive mutations raised the mutant selection window. The wild-type selection window for garenoxacin, levofloxacin, and moxifloxacin was also measured...
  88. ncbi Dimerization of Escherichia coli DNA-gyrase B provides a structural mechanism for activating the ATPase catalytic center
    L Brino
    Institut de Genetique et de Biologie Moleculaire et Cellulaire IGBMC, CNRS INSERM, Universite Louis Pasteur, BP 163, 1 rue Laurent Fries, 67404 Illkirch Cedex, France
    J Biol Chem 275:9468-75. 2000
    ....
  89. doi Comparison of gyrA gene mutations between laboratory-selected ofloxacin-resistant Mycobacterium tuberculosis strains and clinical isolates
    Zhaogang Sun
    Department of Bacteriology and Immunology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Tongzhou District, Beijing 101149, China
    Int J Antimicrob Agents 31:115-21. 2008
    ....
  90. pmc In vitro and in vivo activities of PD 0305970 and PD 0326448, new bacterial gyrase/topoisomerase inhibitors with potent antibacterial activities versus multidrug-resistant gram-positive and fastidious organism groups
    Michael D Huband
    Department of Antibacterial Biology, Pfizer Global Research and Development, 2800 Plymouth Road, Ann Arbor, MI 48105, USA
    Antimicrob Agents Chemother 51:1191-201. 2007
    ..7 mg/kg, respectively). PD 0305970 was also potent in a pneumococcal pneumonia mouse infection model (PD50=3.2 mg/kg) and was 22-fold more potent than levofloxacin...
  91. pmc Clerocidin selectively modifies the gyrase-DNA gate to induce irreversible and reversible DNA damage
    Xiao Su Pan
    Molecular Genetics Group, Molecular and Metabolic Signalling Centre, Division of Basic Medical Sciences, St George s, University of London, Cranmer Terrace, London, SW17 0RE, UK
    Nucleic Acids Res 36:5516-29. 2008
    ..The molecular basis of CL action is poorly understood. We establish by genetic means that CL targets DNA gyrase in the gram-positive bacterium Streptococcus pneumoniae, and promotes gyrase-dependent single- and double-..
  92. 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
    ..This is the first report of a systematic evaluation of a series of aminocoumarins against both gyrase and topo IV. The results give further insight into the structure-activity relationships of aminocoumarin antibiotics...
  93. ncbi An unusually high level of quinolone resistance associated with type II topoisomerase mutations in quinolone resistance-determining regions of Aeromonas caviae isolated from diarrhoeal patients
    Sutapa Sinha
    National Institute of Cholera and Enteric Diseases, Beliaghata, Kolkata 700 010, India
    Res Microbiol 155:827-9. 2004
    ..In resistant strains, double mutations (Ser(83)-->Ile and Asp(87)-->Asn) and a single mutation (Ser(80)-->Ile) were detected in the QRDR of gyrA and parC, respectively...
  94. pmc A mutation in Escherichia coli DNA gyrase conferring quinolone resistance results in sensitivity to drugs targeting eukaryotic topoisomerase II
    Thomas Gruger
    Department of Pharmaceutical Biology and Microbiology, Institute of Pharmacy, University of Hamburg, Germany
    Antimicrob Agents Chemother 48:4495-504. 2004
    ..Many fluoroquinolones are highly specific for bacterial type II topoisomerases and act against both DNA gyrase and topoisomerase IV...
  95. doi Novel multiplex allele-specific PCR assays for the detection of resistance to second-line drugs in Mycobacterium tuberculosis
    Joanna Evans
    Division of Medical Microbiology, Institute of Infectious Diseases and Molecular Medicine, University of Cape Town, Cape Town, South Africa
    J Antimicrob Chemother 65:897-900. 2010
    ..In this study, multiplex allele-specific (MAS)-PCR assays designed to detect the GyrA D94G and rrs A1401G mutations were evaluated for detection of ofloxacin and kanamycin resistance...
  96. ncbi The action of the bacterial toxin microcin B17. Insight into the cleavage-religation reaction of DNA gyrase
    Olivier A Pierrat
    Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Colney, Norwich NR4 7UH, United Kingdom
    J Biol Chem 278:35016-23. 2003
    We have examined the effects of the bacterial toxin microcin B17 (MccB17) on the reactions of Escherichia coli DNA gyrase. MccB17 slows down but does not completely inhibit the DNA supercoiling and relaxation reactions of gyrase...
  97. pmc Twisting of the DNA-binding surface by a beta-strand-bearing proline modulates DNA gyrase activity
    Tung Ju Hsieh
    Institute of Biochemistry and Molecular Biology, College of Medicine, National Taiwan University, Taipei City 100, Taiwan
    Nucleic Acids Res 38:4173-81. 2010
    b>DNA gyrase is the only topoisomerase capable of introducing (-) supercoils into relaxed DNA...
  98. doi Mass spectrometry reveals that the antibiotic simocyclinone D8 binds to DNA gyrase in a "bent-over" conformation: evidence of positive cooperativity in binding
    Marcus J Edwards
    Department of Biological Chemistry, John Innes Centre, Norwich Research Park, Colney, United Kingdom
    Biochemistry 50:3432-40. 2011
    ..Here we present a mass spectrometry study of complexes formed between the A subunit of the topoisomerase DNA gyrase and the bifunctional inhibitor simocyclinone D8 (SD8), an antibiotic isolated from Streptomyces...
  99. ncbi New antibacterial agents derived from the DNA gyrase inhibitor cyclothialidine
    Peter Angehrn
    F Hoffmann La Roche Ltd, Pharmaceutical Division, Preclinical Research, CH 4070 Basel, Switzerland
    J Med Chem 47:1487-513. 2004
    Cyclothialidine (1, Ro 09-1437) is a potent DNA gyrase inhibitor that was isolated from Streptomyces filipinensis NR0484 and is a member of a new family of natural products...
  100. 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
    ..Moreover, to understand the differences in energetics of binding of clorobiocin and novobiocin to the protein, the results from isothermal titration calorimetry are also presented...
  101. pmc A monoclonal antibody that inhibits mycobacterial DNA gyrase by a novel mechanism
    Ujjini H Manjunatha
    Department of Microbiology and Cell Biology, Indian Institute of Science Bangalore, 560 012, India
    Nucleic Acids Res 33:3085-94. 2005
    b>DNA gyrase is a DNA topoisomerase indispensable for cellular functions in bacteria...

Research Grants97

  1. Plasmid-Mediated Quinolone Resistance
    George A Jacoby; Fiscal Year: 2010
    ..Quinolone resistance has traditionally been understood to arise either by mutations that alter DNA gyrase and topoisomerase IV, enzymes that are the targets for quinolone action or by mutations that increase expression ..
  2. Plasmid-Mediated Quinolone Resistance
    David Hooper; Fiscal Year: 2009
    ..Quinolone resistance has traditionally been understood to arise either by mutations that alter DNA gyrase and topoisomerase IV, enzymes that are the targets for quinolone action or by mutations that increase expression ..
  3. QUINOLONE RESISTANCE MECHANISMS IN STAPHYLOCOCCUS AUREUS
    David Hooper; Fiscal Year: 2002
    ..is that topoisomerase IV seems to be the main fluoroquinolone target in the gram positive bacteria rather than DNA gyrase, and this makes it possible to investigate the function and regulation of topoisomerases in ways not possible in ..
  4. Processing and consequences of DNA-protein crosslinks in E. coli
    Kenneth N Kreuzer; Fiscal Year: 2010
    ..The quinolone antibiotics, which target bacterial DNA gyrase, stabilize a reaction intermediate in which the enzyme is covalently attached to a broken DNA molecule via ..
  5. Processing and consequences of DNA-protein crosslinks in E. coli
    Kenneth N Kreuzer; Fiscal Year: 2010
    ..The quinolone antibiotics, which target bacterial DNA gyrase, stabilize a reaction intermediate in which the enzyme is covalently attached to a broken DNA molecule via ..
  6. PATHOBIOCHEMISTRY OF CHLAMYDIA TRACHOMONAS HUMAN SEXUALLY TRANSMITTED DISEASES
    BIBHUTI SINGH; Fiscal Year: 2001
    E. coli microcin B17 (MccB17) is a posttranslationally modified peptide antibiotic that inhibits bacterial DNA gyrase. It contains four oxazole and four thiazole rings and is representative of a broad class of pharmaceutically important ..
  7. Modular Enzymatic Assembly Lines for Antibiotics
    Christopher Walsh; Fiscal Year: 2007
    ..that generate the 5-methylpyrrolycarboxyl moiety that interacts with the ATP site of the GyrB subunit of DNA gyrase. It also focuses on companion 2 His/Asp- Fe (11)enzymes proposed to be cyclopropanation catalyst (coronamic acid ..
  8. ROLE OF TOPOISOMERASES IN DNA REPLICATION
    KENNETH MARIANS; Fiscal Year: 1990
    ..binding protein, the dnaB, dnaC and dnaG (primase) proteins, proteins i, n, n' (replication factor Y), and n", DNA gyrase and topoisomerase I...
  9. LONG RANGE INTERACTIONS IN MU AND BACTERIAL DNA
    NORMAN P HIGGINS; Fiscal Year: 2010
    ..This aim includes a new component involving DNA gyrase biochemistry and genetic methods that evolved from the E. coli/Salmonella species comparison...
  10. LONG RANGE INTERACTIONS IN MU AND BACTERIAL DNA
    NORMAN HIGGINS; Fiscal Year: 2009
    ..This aim includes a new component involving DNA gyrase biochemistry and genetic methods that evolved from the E. coli/Salmonella species comparison...
  11. MECHANISMS OF TOPOISOMERASE POISONS
    Hiroshi Hiasa; Fiscal Year: 2002
    ..in eukaryotes these enzymes are the cellular targets of potent anticancer drugs, whereas in prokaryotes both DNA Gyrase and topoisomerase IV (Topo IV) are targets of the most potent broad-spectrum antibacterial agents (e.q...
  12. Lethal action of fluoroquinolones with non-growing Mycobacterium tuberculosis
    Karl Drlica; Fiscal Year: 2007
    ..tuberculosis. M. tuberculosis DNA gyrase, the molecular target of quinolones, will be purified and used to study biochemical interactions of quinolones ..
  13. Fluoroquinolone Resistance in M. Tuberculosis
    Timothy Sterling; Fiscal Year: 2007
    ..Fluoroquinolone resistance in M. tuberculosis can occur due to a single base-pair mutation in DNA gyrase. However, genetic mutations have not been identified in all fluoroquinolone-resistant M...
  14. Lethal action of fluoroquinolones with non-growing Mycobacterium tuberculosis
    KARL A DRLICA; Fiscal Year: 2010
    ..tuberculosis. M. tuberculosis DNA gyrase, the molecular target of quinolones, will be purified and used to study biochemical interactions of quinolones ..
  15. Lethal action of fluoroquinolones with non-growing Mycobacterium tuberculosis
    Karl Drlica; Fiscal Year: 2009
    ..tuberculosis. M. tuberculosis DNA gyrase, the molecular target of quinolones, will be purified and used to study biochemical interactions of quinolones ..
  16. LONG RANGE INTERACTIONS IN MU AND BACTERIAL DNA
    NORMAN HIGGINS; Fiscal Year: 2001
    ..Two essential genes in bacteria, DNA gyrase and Topoisomerase IV, have both turned up in this screen. Other genes will be mapped and characterized...
  17. Mechanism and Spread of Qnr-Mediated Resistance
    David Hooper; Fiscal Year: 2007
    ..We discovered a plasmid-encoded protein termed Qnr that protects DNA gyrase from quinolone inhibition...
  18. PLASMID MEDIATED QUINOLONE RESISTANCE
    George Jacoby; Fiscal Year: 2001
    ..but the predicted protein (termed Qnr) has similarity to the microcin B17 immunity protein which protects DNA gyrase from microcin inhibition...
  19. ROLE OF TOPOISOMERASES IN DNA METABOLISM
    KENNETH MARIANS; Fiscal Year: 1993
    ..or bidirectional replication, we will study the influence of the three Escherichia coli topoisomerases, DNA gyrase, topoisomerase I (Topo I), and topoisomerase III (Topo III) on the termination and segregation stages of DNA ..
  20. Quinolone Action During Mycobacterial Growth Arrest
    Karl Drlica; Fiscal Year: 2006
    ..b>DNA gyrase mutants have been identified that enhance this minor pathway...
  21. Plasmid-Mediated Quinolone Resistance
    George Jacoby; Fiscal Year: 2007
    ..We discovered a plasmid-encoded protein termed Qnr that protects DNA gyrase from quinolone inhibition...
  22. DNA GYRASE AND QUINOLONE RESISTANCE IN TUBERCULOSIS
    Karl Drlica; Fiscal Year: 2002
    ..First, resistance arises stepwise from mutations in two independent targets, DNA gyrase and DNA topoisomerase IV...
  23. ENZYMATIC REACTION MECHANISMS
    Christopher Walsh; Fiscal Year: 2003
    ..coli DNA gyrase, in which 14 residues (six gly, four ser, four cys) have been posttranslationally modified to four thiazole and ..
  24. CONTROL OF DNA TOPOLOGY
    Yuk Ching Tse Dinh; Fiscal Year: 1999
    ..Eukaryotic topoisomerases and DNA gyrase are known targets for anti-cancer and anti-bacterial drugs...
  25. CONTROL OF DNA TOPOLOGY
    Yuk Ching Tse Dinh; Fiscal Year: 2003
    ..DNA religation would lead to cell killing in a mechanism similar to those of many drugs targeting bacterial DNA gyrase and human topoisomerases...
  26. DNA GYRASE AND QUINOLONE RESISTANCE IN TUBERCULOSIS
    Karl Drlica; Fiscal Year: 2007
    ..abstract_text> ..
  27. DNA GYRASE AND QUINOLONE RESISTANCE IN TUBERCULOSIS
    Karl Drlica; Fiscal Year: 2006
    ..abstract_text> ..
  28. Principles of Protein Mimicry of DNA
    MICHAEL D BRENOWITZ; Fiscal Year: 2010
    ..to the biological role of MfpA is suggested by its ability to confer resistance to fluoro- quinolones by binding DNA gyrase thereby inhibiting its function...
  29. Principles of Protein Mimicry of DNA
    Michael Brenowitz; Fiscal Year: 2009
    ..to the biological role of MfpA is suggested by its ability to confer resistance to fluoro- quinolones by binding DNA gyrase thereby inhibiting its function...
  30. BIOCHEMICAL STUDIES OF PHAGE MU
    NORMAN HIGGINS; Fiscal Year: 1990
    ..stimulates lytic transcription and decreases repressor transcription; thus, the virus is sensitive to DNA gyrase activity of the host. A binding site for a type II DNA binding protein of E...