dna gyrase


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 of two A and two B subunits. In the presence of ATP, gyrase is able to convert the relaxed circular DNA duplex into a superhelix. In the absence of ATP, supercoiled DNA is relaxed by DNA gyrase.

Top Publications

  1. Karczmarczyk M, Martins M, Quinn T, Leonard N, Fanning S. Mechanisms of fluoroquinolone resistance in Escherichia coli isolates from food-producing animals. Appl Environ Microbiol. 2011;77:7113-20 pubmed publisher
    ..This study identified multiple mechanisms that likely contribute to resistance to quinolone-based drugs in the field isolates studied. ..
  2. Pantel A, Petrella S, Veziris N, Brossier F, Bastian S, Jarlier V, et al. Extending the definition of the GyrB quinolone resistance-determining region in Mycobacterium tuberculosis DNA gyrase for assessing fluoroquinolone resistance in M. tuberculosis. Antimicrob Agents Chemother. 2012;56:1990-6 pubmed publisher
    ..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...
  3. Brvar M, Perdih A, Hodnik V, Renko M, Anderluh G, Jerala R, et al. In silico discovery and biophysical evaluation of novel 5-(2-hydroxybenzylidene) rhodanine inhibitors of DNA gyrase B. Bioorg Med Chem. 2012;20:2572-80 pubmed publisher
    Bacterial DNA gyrase is an established and validated target for the development of novel antibacterials. In our previous work, we identified a novel series of bacterial gyrase inhibitors from the class of 4-(2,4-dihydroxyphenyl) thiazoles...
  4. Zaluga J, Heylen K, Van Hoorde K, Hoste B, Van Vaerenbergh J, Maes M, et al. GyrB sequence analysis and MALDI-TOF MS as identification tools for plant pathogenic Clavibacter. Syst Appl Microbiol. 2011;34:400-7 pubmed publisher
    ..Our study suggests that proteomic analysis using MALDI-TOF MS and gyrB sequence are powerful diagnostic tools for the accurate identification of Clavibacter plant pathogens. ..
  5. Pantel A, Petrella S, Matrat S, Brossier F, Bastian S, Reitter D, et al. DNA gyrase inhibition assays are necessary to demonstrate fluoroquinolone resistance secondary to gyrB mutations in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2011;55:4524-9 pubmed publisher
    The main mechanism of fluoroquinolone (FQ) resistance in Mycobacterium tuberculosis is mutation in DNA gyrase (GyrA(2)GyrB(2)), especially in gyrA...
  6. Wu J, Zhang Z, Mitchenall L, Maxwell A, Deng J, Zhang H, et al. The dimer state of GyrB is an active form: implications for the initial complex assembly and processive strand passage. Nucleic Acids Res. 2011;39:8488-502 pubmed publisher
    In a previous study, we presented the dimer structure of DNA gyrase B' domain (GyrB C-terminal domain) from Mycobacterium tuberculosis and proposed a 'sluice-like' model for T-segment transport...
  7. Bates A, Berger J, Maxwell A. The ancestral role of ATP hydrolysis in type II topoisomerases: prevention of DNA double-strand breaks. Nucleic Acids Res. 2011;39:6327-39 pubmed publisher
    ..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 ..
  8. Trzoss M, Bensen D, Li X, Chen Z, Lam T, Zhang J, et al. Pyrrolopyrimidine inhibitors of DNA gyrase B (GyrB) and topoisomerase IV (ParE), Part II: development of inhibitors with broad spectrum, Gram-negative antibacterial activity. Bioorg Med Chem Lett. 2013;23:1537-43 pubmed publisher
    The structurally related bacterial topoisomerases DNA gyrase (GyrB) and topoisomerase IV (ParE) have long been recognized as prime candidates for the development of broad spectrum antibacterial agents...
  9. Brvar M, Perdih A, Renko M, Anderluh G, Turk D, Solmajer T. Structure-based discovery of substituted 4,5'-bithiazoles as novel DNA gyrase inhibitors. J Med Chem. 2012;55:6413-26 pubmed publisher
    Bacterial DNA gyrase is a well-established and validated target for the development of novel antibacterials...

More Information


  1. Basu A, Schoeffler A, Berger J, Bryant Z. ATP binding controls distinct structural transitions of Escherichia coli DNA gyrase in complex with DNA. Nat Struct Mol Biol. 2012;19:538-46, S1 pubmed publisher
    b>DNA gyrase is a molecular motor that harnesses the free energy of ATP hydrolysis to introduce negative supercoils into DNA. A critical step in this reaction is the formation of a chiral DNA wrap...
  2. Tretter E, Berger J. Mechanisms for defining supercoiling set point of DNA gyrase orthologs: I. A nonconserved acidic C-terminal tail modulates Escherichia coli gyrase activity. J Biol Chem. 2012;287:18636-44 pubmed publisher
    ..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. ..
  3. Agrawal A, Rou M, Spitzfaden C, Petrella S, Aubry A, Hann M, et al. Mycobacterium tuberculosis DNA gyrase ATPase domain structures suggest a dissociative mechanism that explains how ATP hydrolysis is coupled to domain motion. Biochem J. 2013;456:263-73 pubmed publisher
    b>DNA gyrase, a type II topoisomerase, regulates DNA topology by creating a double-stranded break in one DNA duplex and transporting another DNA duplex [T-DNA (transported DNA)] through this break...
  4. Ghilarov D, Serebryakova M, Shkundina I, Severinov K. A major portion of DNA gyrase inhibitor microcin B17 undergoes an N,O-peptidyl shift during synthesis. J Biol Chem. 2011;286:26308-18 pubmed publisher
    Microcin B17 (McB) is a 43-amino acid antibacterial peptide targeting the DNA gyrase. The McB precursor is ribosomally produced and then post-translationally modified by the McbBCD synthase...
  5. Collin F, Karkare S, Maxwell A. Exploiting bacterial DNA gyrase as a drug target: current state and perspectives. Appl Microbiol Biotechnol. 2011;92:479-97 pubmed publisher
    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...
  6. Sherer B, Hull K, Green O, Basarab G, Hauck S, Hill P, et al. Pyrrolamide DNA gyrase inhibitors: optimization of antibacterial activity and efficacy. Bioorg Med Chem Lett. 2011;21:7416-20 pubmed publisher
    The pyrrolamides are a new class of antibacterial agents targeting DNA gyrase, an essential enzyme across bacterial species and inhibition results in the disruption of DNA synthesis and subsequently, cell death...
  7. Aboul Fadl T, Abdel Aziz H, Abdel Hamid M, Elsaman T, Thanassi J, Pucci M. Schiff bases of indoline-2,3-dione: potential novel inhibitors of Mycobacterium tuberculosis (Mtb) DNA gyrase. Molecules. 2011;16:7864-79 pubmed publisher
    ..The orientation and the ligand-receptor interactions of such molecules within the Mtb DNA gyrase A subunit active site were investigated applying a multi-step docking protocol using Molecular Operating ..
  8. Karkare S, Yousafzai F, Mitchenall L, Maxwell A. The role of Ca²? in the activity of Mycobacterium tuberculosis DNA gyrase. Nucleic Acids Res. 2012;40:9774-87 pubmed publisher
    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 ..
  9. Uria Nickelsen M, Blodgett A, Kamp H, EAKIN A, Sherer B, Green O. Novel DNA gyrase inhibitors: microbiological characterisation of pyrrolamides. Int J Antimicrob Agents. 2013;41:28-35 pubmed publisher
    Pyrrolamides are a novel class of antibacterial agents that target DNA gyrase, resulting in inhibition of DNA synthesis and bacterial cell death...
  10. Gübeli R, Ehrbar M, Fussenegger M, Friedrich C, Weber W. Synthesis and characterization of PEG-based drug-responsive biohybrid hydrogels. Macromol Rapid Commun. 2012;33:1280-5 pubmed publisher
    ..The switchable properties of this PEG-based hydrogel are favorable for future applications in tissue engineering and as externally controlled drug depot. ..
  11. Gubaev A, Klostermeier D. DNA-induced narrowing of the gyrase N-gate coordinates T-segment capture and strand passage. Proc Natl Acad Sci U S A. 2011;108:14085-90 pubmed publisher
    b>DNA gyrase introduces negative supercoils into DNA in an ATP-dependent reaction. DNA supercoiling is catalyzed by a strand-passage mechanism, in which a T-segment of DNA is passed through the gap in a transiently cleaved G-segment...
  12. Gironde S, Manceau C. Housekeeping gene sequencing and multilocus variable-number tandem-repeat analysis to identify subpopulations within Pseudomonas syringae pv. maculicola and Pseudomonas syringae pv. tomato that correlate with host specificity. Appl Environ Microbiol. 2012;78:3266-79 pubmed publisher
    ..tomato appear multiclonal, as they did not diverge from a single common ancestral group within the ancestral P. syringae genomospecies 3, and suggests that pathovar specificity within P. syringae may be due to independent genetic events...
  13. Papillon J, M n tret J, Batisse C, H lye R, Schultz P, Potier N, et al. Structural insight into negative DNA supercoiling by DNA gyrase, a bacterial type 2A DNA topoisomerase. Nucleic Acids Res. 2013;41:7815-27 pubmed publisher
    ..The bacterial DNA gyrase, a target for broad-spectrum antibiotics, is the sole Topo2A enzyme able to introduce negative supercoils...
  14. Monego F, Duarte R, Biondo A. gyrA and gyrB gene mutation in ciprofloxacin-resistant Mycobacterium massiliense clinical isolates from Southern Brazil. Microb Drug Resist. 2012;18:1-6 pubmed publisher
    ..No gyrB mutation was observed in all tested M. massiliense isolates. In conclusion, our results have shown that mutations of gyrA codon 90 are frequent and may constitute an important mechanism of resistance to FQ in M. massiliense. ..
  15. Tari L, Trzoss M, Bensen D, Li X, Chen Z, Lam T, et al. Pyrrolopyrimidine inhibitors of DNA gyrase B (GyrB) and topoisomerase IV (ParE). Part I: Structure guided discovery and optimization of dual targeting agents with potent, broad-spectrum enzymatic activity. Bioorg Med Chem Lett. 2013;23:1529-36 pubmed publisher
    The bacterial topoisomerases DNA gyrase (GyrB) and topoisomerase IV (ParE) are essential enzymes that control the topological state of DNA during replication...
  16. Shafreen R, Selvaraj C, Singh S, Pandian S. Exploration of fluoroquinolone resistance in Streptococcus pyogenes: comparative structure analysis of wild-type and mutant DNA gyrase. J Mol Recognit. 2013;26:276-85 pubmed publisher
    ..In the present study, ligands were tested for their inhibitory activity against DNA gyrase of Streptococcus pyogenes involved in DNA replication...
  17. Taylor J, Burton N, Maxwell A. High-throughput microtitre plate-based assay for DNA topoisomerases. Methods Mol Biol. 2012;815:229-39 pubmed publisher
    ..Due to its high speed of sample analysis and reduced sample handling over conventional gel-based techniques, this assay can be used to screen chemical libraries for novel inhibitors of topoisomerases. ..
  18. Kim H, Nakajima C, Yokoyama K, Rahim Z, Kim Y, Oguri H, et al. Impact of the E540V amino acid substitution in GyrB of Mycobacterium tuberculosis on quinolone resistance. Antimicrob Agents Chemother. 2011;55:3661-7 pubmed publisher
    ..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)...
  19. Tao J, Han J, Wu H, Hu X, Deng J, Fleming J, et al. Mycobacterium fluoroquinolone resistance protein B, a novel small GTPase, is involved in the regulation of DNA gyrase and drug resistance. Nucleic Acids Res. 2013;41:2370-81 pubmed publisher
    b>DNA gyrase plays a vital role in resolving DNA topological problems and is the target of antibiotics such as fluoroquinolones...
  20. Eakin A, Green O, Hales N, Walkup G, Bist S, Singh A, et al. Pyrrolamide DNA gyrase inhibitors: fragment-based nuclear magnetic resonance screening to identify antibacterial agents. Antimicrob Agents Chemother. 2012;56:1240-6 pubmed publisher
    b>DNA gyrase is an essential enzyme in bacteria, and its inhibition results in the disruption of DNA synthesis and, subsequently, cell death. The pyrrolamides are a novel class of antibacterial agents targeting DNA gyrase...
  21. Lara Ortíz T, Castro Dorantes J, Ramírez Santos J, Gómez Eichelmann M. Role of the DnaK-ClpB bichaperone system in DNA gyrase reactivation during a severe heat-shock response in Escherichia coli. Can J Microbiol. 2012;58:195-9 pubmed publisher
    ..b>DNA gyrase, proteins synthesized during heat stress, and chaperone DnaK have been proposed to participate in this recovery...
  22. Maruri F, Sterling T, Kaiga A, Blackman A, van der Heijden Y, Mayer C, et al. A systematic review of gyrase mutations associated with fluoroquinolone-resistant Mycobacterium tuberculosis and a proposed gyrase numbering system. J Antimicrob Chemother. 2012;67:819-31 pubmed publisher
    ..A review of mutations in DNA gyrase, the fluoroquinolone target, is needed to improve the molecular detection of resistance...
  23. Levican A, Collado L, Aguilar C, Yustes C, Diéguez A, Romalde J, et al. Arcobacter bivalviorum sp. nov. and Arcobacter venerupis sp. nov., new species isolated from shellfish. Syst Appl Microbiol. 2012;35:133-8 pubmed publisher
  24. Yokoyama K, Kim H, Mukai T, Matsuoka M, Nakajima C, Suzuki Y. Impact of amino acid substitutions in B subunit of DNA gyrase in Mycobacterium leprae on fluoroquinolone resistance. PLoS Negl Trop Dis. 2012;6:e1838 pubmed publisher
    ..FQs are known to interact with both A and B subunits of DNA gyrase and inhibit supercoiling activity of this enzyme...
  25. Kale M, Raichurkar A, P S, Waterson D, MCKINNEY D, Manjunatha M, et al. Thiazolopyridine ureas as novel antitubercular agents acting through inhibition of DNA Gyrase B. J Med Chem. 2013;56:8834-48 pubmed publisher
    ..of thiazolopyridine ureas as a novel scaffold with antitubercular activity acting through inhibition of DNA Gyrase B (GyrB) ATPase...
  26. Taylor J, Mitchenall L, Rejzek M, Field R, Maxwell A. Application of a novel microtitre plate-based assay for the discovery of new inhibitors of DNA gyrase and DNA topoisomerase VI. PLoS ONE. 2013;8:e58010 pubmed publisher
    ..A library of 960 compounds was screened against Escherichia coli DNA gyrase and archaeal Methanosarcina mazei DNA topoisomerase VI...
  27. Garcia M, Raymond J, Garnier M, Cremniter J, Burucoa C. Distribution of spontaneous gyrA mutations in 97 fluoroquinolone-resistant Helicobacter pylori isolates collected in France. Antimicrob Agents Chemother. 2012;56:550-1 pubmed publisher
  28. Malik S, WILLBY M, Sikes D, Tsodikov O, Posey J. New insights into fluoroquinolone resistance in Mycobacterium tuberculosis: functional genetic analysis of gyrA and gyrB mutations. PLoS ONE. 2012;7:e39754 pubmed publisher
    ..The results from this study provide support for the inclusion of the QRDR of gyrB in molecular assays used to detect fluoroquinolone resistance in M. tuberculosis. ..
  29. Suzuki Y, Nakajima C, Tamaru A, Kim H, Matsuba T, Saito H. Sensitivities of ciprofloxacin-resistant Mycobacterium tuberculosis clinical isolates to fluoroquinolones: role of mutant DNA gyrase subunits in drug resistance. Int J Antimicrob Agents. 2012;39:435-9 pubmed publisher
    ..Double gyrA mutations as well as mutations in both gyrA and gyrB correlated with increased resistance to all fluoroquinolones. ..
  30. Alt S, Mitchenall L, Maxwell A, Heide L. Inhibition of DNA gyrase and DNA topoisomerase IV of Staphylococcus aureus and Escherichia coli by aminocoumarin antibiotics. J Antimicrob Chemother. 2011;66:2061-9 pubmed publisher
    Aminocoumarin antibiotics are potent inhibitors of bacterial DNA gyrase. We investigated the inhibitory and antibacterial activity of naturally occurring aminocoumarin antibiotics and six structural analogues (novclobiocins) against DNA ..
  31. Lee C, Wetzel K, Buckley T, Wozniak D, Lee J. Rapid and sensitive detection of Pseudomonas aeruginosa in chlorinated water and aerosols targeting gyrB gene using real-time PCR. J Appl Microbiol. 2011;111:893-903 pubmed publisher
    ..This approach can be easily utilized as a platform technology for the detection of other types of micro-organisms, especially for those that are transmitted via water and aerosol routes, such as Legionella pneumophila. ..
  32. Cui Z, Wang J, Lu J, Huang X, Hu Z. Association of mutation patterns in gyrA/B genes and ofloxacin resistance levels in Mycobacterium tuberculosis isolates from East China in 2009. BMC Infect Dis. 2011;11:78 pubmed publisher
    ..tuberculosis, there were no associations of different mutation patterns in gyrA/B and the level of ofloxacin resistance in M. tuberculosis isolates from East China in 2009. ..
  33. Tretter E, Berger J. 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. J Biol Chem. 2012;287:18645-54 pubmed publisher
    ..Our observations demonstrate that gyrase has been modified in multiple ways throughout evolution to fine-tune its specific catalytic properties. ..
  34. Rovinskiy N, Agbleke A, Chesnokova O, Pang Z, Higgins N. Rates of gyrase supercoiling and transcription elongation control supercoil density in a bacterial chromosome. PLoS Genet. 2012;8:e1002845 pubmed publisher
    ..The observed link between RNA polymerase elongation speed and gyrase turnover suggests that bacteria with fast growth rates may generate higher supercoil densities than slow growing species...
  35. Hu Y, Mathema B, Wang W, Kreiswirth B, Jiang W, Xu B. Population-based investigation of fluoroquinolones resistant tuberculosis in rural eastern China. Tuberculosis (Edinb). 2011;91:238-43 pubmed publisher
    ..The relatively low level of clustering among FQ-resistant strains suggests most are acquired de novo, likely due to widespread FQ use. ..
  36. Lanz M, Klostermeier D. Guiding strand passage: DNA-induced movement of the gyrase C-terminal domains defines an early step in the supercoiling cycle. Nucleic Acids Res. 2011;39:9681-94 pubmed publisher
    b>DNA gyrase catalyzes ATP-dependent negative supercoiling of DNA in a strand passage mechanism...
  37. Dimitrov T, Dashti A, Albaksami O, Udo E, Jadaon M, Albert M. Ciprofloxacin-resistant Salmonella enterica serovar typhi from Kuwait with novel mutations in gyrA and parC genes. J Clin Microbiol. 2009;47:208-11 pubmed publisher
    ..Both isolates had three novel gyrA mutations (55-Leu-->Trp, 87-Asp-->Ala, and 106-Gln-->Arg) and three novel parC mutations (84-Glu-->Lys, 106-Trp-->Gly, and 128-Tyr-->Asp). ..
  38. Edwards M, Williams M, Maxwell A, McKay A. Mass spectrometry reveals that the antibiotic simocyclinone D8 binds to DNA gyrase in a "bent-over" conformation: evidence of positive cooperativity in binding. Biochemistry. 2011;50:3432-40 pubmed publisher
    ..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...
  39. Kirby B, Everest G, Meyers P. Phylogenetic analysis of the genus Kribbella based on the gyrB gene: proposal of a gyrB-sequence threshold for species delineation in the genus Kribbella. Antonie Van Leeuwenhoek. 2010;97:131-42 pubmed publisher
  40. Trovatti E, Cotrim C, Garrido S, Barros R, Marchetto R. Peptides based on CcdB protein as novel inhibitors of bacterial topoisomerases. Bioorg Med Chem Lett. 2008;18:6161-4 pubmed publisher
    ..ccd toxin-antitoxin system of the F plasmid encodes CcdB, a protein that poisons the essential Escherichia coli DNA gyrase, unique type IIA topoisomerase able to introduce negative supercoils into DNA...
  41. Shapiro A, Jahic H, Prasad S, Ehmann D, Thresher J, Gao N, et al. A homogeneous, high-throughput fluorescence anisotropy-based DNA supercoiling assay. J Biomol Screen. 2010;15:1088-98 pubmed publisher
    ..coli DNA gyrase, and inhibition of gyrase by fluoroquinolones and nalidixic acid.
  42. Xiong X, Bromley E, Oelschlaeger P, Woolfson D, Spencer J. Structural insights into quinolone antibiotic resistance mediated by pentapeptide repeat proteins: conserved surface loops direct the activity of a Qnr protein from a gram-negative bacterium. Nucleic Acids Res. 2011;39:3917-27 pubmed publisher
    Quinolones inhibit bacterial type II DNA topoisomerases (e.g. DNA gyrase) and are among the most important antibiotics in current use. However, their efficacy is now being threatened by various plasmid-mediated resistance determinants...
  43. Chakravorty S, Aladegbami B, Thoms K, Lee J, Lee E, Rajan V, et al. 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. J Clin Microbiol. 2011;49:932-40 pubmed publisher
    ..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. ..
  44. Hsieh T, Yen T, Lin T, Chang H, Huang S, Hsu C, et al. Twisting of the DNA-binding surface by a beta-strand-bearing proline modulates DNA gyrase activity. Nucleic Acids Res. 2010;38:4173-81 pubmed publisher
    b>DNA gyrase is the only topoisomerase capable of introducing (-) supercoils into relaxed DNA...
  45. Yuan J, Sterckx Y, Mitchenall L, Maxwell A, Loris R, Waldor M. Vibrio cholerae ParE2 poisons DNA gyrase via a mechanism distinct from other gyrase inhibitors. J Biol Chem. 2010;285:40397-408 pubmed publisher
    b>DNA gyrase is an essential bacterial enzyme required for the maintenance of chromosomal DNA topology...
  46. Cambau E, Matrat S, Pan X, Roth Dit Bettoni R, Corbel C, Aubry A, et al. Target specificity of the new fluoroquinolone besifloxacin in Streptococcus pneumoniae, Staphylococcus aureus and Escherichia coli. J Antimicrob Chemother. 2009;63:443-50 pubmed publisher
    ..pneumoniae and E. coli DNA gyrase and topoisomerase IV enzymes. Enzyme assays showed similar besifloxacin activity against S...
  47. Edwards M, Flatman R, Mitchenall L, Stevenson C, Le T, Clarke T, et al. A crystal structure of the bifunctional antibiotic simocyclinone D8, bound to DNA gyrase. Science. 2009;326:1415-8 pubmed publisher
    Simocyclinones are bifunctional antibiotics that inhibit bacterial DNA gyrase by preventing DNA binding to the enzyme...
  48. Gubaev A, Hilbert M, Klostermeier D. The DNA-gate of Bacillus subtilis gyrase is predominantly in the closed conformation during the DNA supercoiling reaction. Proc Natl Acad Sci U S A. 2009;106:13278-83 pubmed publisher
    ..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. ..
  49. Duong D, Nguyen T, Nguyen T, Dai V, Dang T, Vo S, et al. Beijing genotype of Mycobacterium tuberculosis is significantly associated with high-level fluoroquinolone resistance in Vietnam. Antimicrob Agents Chemother. 2009;53:4835-9 pubmed publisher
  50. Johnsen L, Weigel C, von Kries J, Møller M, Skarstad K. A novel DNA gyrase inhibitor rescues Escherichia coli dnaAcos mutant cells from lethal hyperinitiation. J Antimicrob Chemother. 2010;65:924-30 pubmed publisher
    ..by growth assays specific for replication proteins as well as an in vitro assay of the activity of purified DNA gyrase. One of the compounds that tested positive in this screening was the benzazepine derivate (+/-)-6-chloro-PB ..
  51. Black M, Stachyra T, Platel D, Girard A, Claudon M, Bruneau J, et al. Mechanism of action of the antibiotic NXL101, a novel nonfluoroquinolone inhibitor of bacterial type II topoisomerases. Antimicrob Agents Chemother. 2008;52:3339-49 pubmed publisher
    NXL101 is one of a new class of quinoline antibacterial DNA gyrase and topoisomerase IV inhibitors showing potent activity against gram-positive bacteria, including methicillin- and fluoroquinolone-resistant strains...
  52. Robertson G, Bonventre E, Doyle T, Du Q, Duncan L, Morris T, et al. In vitro evaluation of CBR-2092, a novel rifamycin-quinolone hybrid antibiotic: studies of the mode of action in Staphylococcus aureus. Antimicrob Agents Chemother. 2008;52:2313-23 pubmed publisher
    ..exhibited rifampin-like potency as an inhibitor of RNA polymerase, was an equipotent (balanced) inhibitor of DNA gyrase and DNA topoisomerase IV, and retained activity against a prevalent quinolone-resistant variant...
  53. Okumura R, Hirata T, Onodera Y, Hoshino K, Otani T, Yamamoto T. Dual-targeting properties of the 3-aminopyrrolidyl quinolones, DC-159a and sitafloxacin, against DNA gyrase and topoisomerase IV: contribution to reducing in vitro emergence of quinolone-resistant Streptococcus pneumoniae. J Antimicrob Chemother. 2008;62:98-104 pubmed publisher
    ..MIC ratios against single gyrA or parC mutants relative to the wild-type strain and low IC(50) ratios against DNA gyrase and topoisomerase IV...
  54. Bax B, Chan P, Eggleston D, Fosberry A, Gentry D, Gorrec F, et al. Type IIA topoisomerase inhibition by a new class of antibacterial agents. Nature. 2010;466:935-40 pubmed publisher
    ..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 ..
  55. Poissy J, Aubry A, Fernandez C, Lott M, Chauffour A, Jarlier V, et al. Should moxifloxacin be used for the treatment of extensively drug-resistant tuberculosis? An answer from a murine model. Antimicrob Agents Chemother. 2010;54:4765-71 pubmed publisher
    ..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...
  56. Kim H, Park C, Kim C, Kim E, Jacoby G, Hooper D. Prevalence of plasmid-mediated quinolone resistance determinants over a 9-year period. Antimicrob Agents Chemother. 2009;53:639-45 pubmed publisher
  57. Lau R, Ho P, Kao R, Yew W, Lau T, Cheng V, et al. Molecular characterization of fluoroquinolone resistance in Mycobacterium tuberculosis: functional analysis of gyrA mutation at position 74. Antimicrob Agents Chemother. 2011;55:608-14 pubmed publisher
    ..A number of gyrA mutations (Glu21Gln, Ser95Thr, and Gly668Asp) were also characterized to be natural polymorphisms not associated with fluoroquinolone resistance. ..
  58. Matsuoka M, Suzuki Y, Garcia I, Fafutis Morris M, Vargas Gonzalez A, Carreño Martinez C, et al. Possible mode of emergence for drug-resistant leprosy is revealed by an analysis of samples from Mexico. Jpn J Infect Dis. 2010;63:412-6 pubmed
    ..In addition, all three drug resistance-related mutations were found in only one of the two earlobes of the patients concerned, suggesting a possible pathway for the spread of drug-resistant M. leprae. ..
  59. Mokrousov I, Otten T, Manicheva O, Potapova Y, Vishnevsky B, Narvskaya O, et al. Molecular characterization of ofloxacin-resistant Mycobacterium tuberculosis strains from Russia. Antimicrob Agents Chemother. 2008;52:2937-9 pubmed publisher
    ..tuberculosis. ..
  60. Pan X, Gould K, Fisher L. Probing the differential interactions of quinazolinedione PD 0305970 and quinolones with gyrase and topoisomerase IV. Antimicrob Agents Chemother. 2009;53:3822-31 pubmed publisher
    Quinazoline-2,4-diones, such as PD 0305970, are new DNA gyrase and topoisomerase IV (topo IV) inhibitors with potent activity against gram-positive pathogens, including quinolone-resistant isolates...
  61. Pan X, Dias M, Palumbo M, Fisher L. Clerocidin selectively modifies the gyrase-DNA gate to induce irreversible and reversible DNA damage. Nucleic Acids Res. 2008;36:5516-29 pubmed publisher
    ..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-..
  62. Bansal S, Tandon V. Contribution of mutations in DNA gyrase and topoisomerase IV genes to ciprofloxacin resistance in Escherichia coli clinical isolates. Int J Antimicrob Agents. 2011;37:253-5 pubmed publisher
    b>DNA gyrase (GyrA and GyrB) and topoisomerase IV (ParC and ParE) are the two essential type II topoisomerases in Escherichia coli. These enzymes act via inhibition of DNA replication...
  63. Namboodiri S, Opintan J, Lijek R, Newman M, Okeke I. Quinolone resistance in Escherichia coli from Accra, Ghana. BMC Microbiol. 2011;11:44 pubmed publisher
    ..Containment strategies to limit the spread of quinolone-resistant E. coli need to be deployed to conserve quinolone effectiveness and promote alternatives to their use. ..
  64. Angehrn P, Goetschi E, Gmuender H, Hebeisen P, Hennig M, Kuhn B, et al. A new DNA gyrase inhibitor subclass of the cyclothialidine family based on a bicyclic dilactam-lactone scaffold. Synthesis and antibacterial properties. J Med Chem. 2011;54:2207-24 pubmed publisher
    The DNA gyrase inhibitor cyclothialidine had been shown to be a valuable lead structure for the discovery of new antibacterial classes able to overcome bacterial resistance to clinically used drugs...