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EcoSal Plus

Domain 4:

Synthesis and Processing of Macromolecules

DNA Topoisomerases

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  • Authors: Natassja G. Bush1, Katherine Evans-Roberts2, and Anthony Maxwell3
  • Editor: Susan T. Lovett4
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Biological Chemistry, John Innes Centre, Norwich NR4 7UH, United Kingdom; 2: Babraham Institute Enterprise Ltd., Babraham Research Campus, Cambridge CB22 3AT, United Kingdom; 3: Department of Biological Chemistry, John Innes Centre, Norwich NR4 7UH, United Kingdom; 4: Brandeis University, Waltham, MA
  • Received 01 October 2014 Accepted 09 October 2014 Published 17 April 2015
  • Address correspondence to Anthony Maxwell, tony.maxwell@jic.ac.uk
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  • Abstract:

    DNA topoisomerases are enzymes that control the topology of DNA in all cells. There are two types, I and II, classified according to whether they make transient single- or double-stranded breaks in DNA. Their reactions generally involve the passage of a single- or double-strand segment of DNA through this transient break, stabilized by DNA-protein covalent bonds. All topoisomerases can relax DNA, but DNA gyrase, present in all bacteria, can also introduce supercoils into DNA. Because of their essentiality in all cells and the fact that their reactions proceed via DNA breaks, topoisomerases have become important drug targets; the bacterial enzymes are key targets for antibacterial agents. This article discusses the structure and mechanism of topoisomerases and their roles in the bacterial cell. Targeting of the bacterial topoisomerases by inhibitors, including antibiotics in clinical use, is also discussed.

  • Citation: Bush N, Evans-Roberts K, Maxwell A. 2015. DNA Topoisomerases, EcoSal Plus 2015; doi:10.1128/ecosalplus.ESP-0010-2014

Key Concept Ranking

Type IIA Topoisomerase
0.5030828
Type IIB Topoisomerase
0.49928114
Type I Topoisomerase
0.4917055
0.5030828

Article Version

This article is an updated version of the following content:

References

1. Watson JD, Crick FH. 1953. Genetical implications of the structure of deoxyribonucleic acid. Nature 171:964–967. [PubMed][CrossRef]
2. Bates AD, Maxwell A. 2005. DNA Topology. Oxford University Press, Oxford, United Kingdom.
3. Deweese JE, Osheroff MA, Osheroff N. 2008. DNA topology and topoisomerases: teaching a “knotty” subject. Biochem Mol Biol Educ 37:2–10. [PubMed][CrossRef]
4. Sissi C, Palumbo M. 2010. In front of and behind the replication fork: bacterial type IIA topoisomerases. Cell Mol Life Sci 67:2001–2024. [PubMed][CrossRef]
5. Vos SM, Tretter EM, Schmidt BH, Berger JM. 2011. All tangled up: how cells direct, manage and exploit topoisomerase function. Nat Rev Mol Cell Biol 12:827–841. [PubMed][CrossRef]
6. Wang JC. 2009. Untangling the Double Helix: DNA Entanglement and the Action of the DNA Topoisomerases. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
7. Ghilarov DA, Shkundina IS. 2012. DNA topoisomerases and their functions in a cell. Mol Biol 46:47–57. [CrossRef]
8. Schvartzman JB, Stasiak A. 2004. A topological view of the replicon. EMBO Rep 5:256–261. [PubMed][CrossRef]
9. Postow L, Crisona NJ, Peter BJ, Hardy CD, Cozzarelli NR. 2001. Topological challenges to DNA replication: conformations at the fork. Proc Natl Acad Sci USA 98:8219–8226. [PubMed][CrossRef]
10. Ullsperger CJ, Vologodskii AV, Cozzarelli NR. 1995. Unlinking of DNA by topoisomerases during DNA replication, p 115–142. In Eckstein F, Lilley DMJ (ed), Nucleic Acids and Molecular Biology, vol 9. Springer-Verlag, Berlin, Germany. [CrossRef]
11. Zechiedrich EL, Cozzarelli NR. 1995. Roles of topoisomerase IV and DNA gyrase in DNA unlinking during replication in Escherichia coli. Genes Dev 9:2859–2869. [PubMed][CrossRef]
12. Liu LF, Wang JC. 1987. Supercoiling of the DNA template during transcription. Proc Natl Acad Sci USA 84:7024–7027. [PubMed][CrossRef]
13. Lockshon D, Morris DR. 1983. Positively supercoiled plasmid DNA is produced by treatment of Escherichia coli with DNA gyrase inhibitors. Nucleic Acids Res 11:2999–3017. [PubMed][CrossRef]
14. Pruss G, Drlica K. 1986. Topoisomerase I mutants: the gene on pBR322 that encodes resistance to tetracycline affects plasmid DNA supercoiling. Proc Natl Acad Sci USA 83:8952–8956. [PubMed][CrossRef]
15. Dorman CJ. 2008. Regulation of transcription in bacteria by DNA supercoiling, p 155–177. In El-Sharoud W (ed), Bacterial Physiology: a Molecular Approach. Springer-Verlag, Berlin, Germany. [CrossRef]
16. Lilley DMJ, Chen D, Bowater RP. 1996. DNA supercoiling and transcription: topological coupling of promoters. Q Rev Biophys 29:203–225. [PubMed][CrossRef]
17. Menzel R, Gellert M. 1983. Regulation of the genes for E. coli DNA gyrase: homeostatic control of DNA supercoiling. Cell 34:105–113. [PubMed][CrossRef]
18. Zechiedrich EL, Khodursky AB, Bachellier S, Schneider R, Chen D, Lilley DMJ, Cozzarelli NR. 2000. Roles of topoisomerases in maintaining steady-state DNA supercoiling in Escherichia coli. J Biol Chem 275:8103–8113. [PubMed][CrossRef]
19. Liu LF, Liu C-C, Alberts BM. 1980. Type II DNA topoisomerases: enzymes that can unknot a topologically knotted DNA molecule via a reversible double-strand break. Cell 19:697–707. [PubMed][CrossRef]
20. Wang JC. 1971. Interaction between DNA and an Escherichia coli protein ω. J Mol Biol 55:523–533. [PubMed][CrossRef]
21. Tse Y, Wang JC. 1980. E. coli and M. luteus DNA topoisomerase I can catalyze catenation of decatenation of double-stranded DNA rings. Cell 22:269–276. [PubMed][CrossRef]
22. Lima CD, Wang JC, Mondragón A. 1994. Three-dimensional structure of the 67K N-terminal fragment of E. coli DNA topoisomerase I. Nature 367:138–146. [PubMed][CrossRef]
23. Zhang Z, Cheng B, Tse-Dinh YC. 2011. Crystal structure of a covalent intermediate in DNA cleavage and rejoining by Escherichia coli DNA topoisomerase I. Proc Natl Acad Sci USA 108:6939–6944. [PubMed][CrossRef]
24. Ahmed W, Bhat AG, Leelaram MN, Menon S, Nagaraja V. 2013. Carboxyl terminal domain basic amino acids of mycobacterial topoisomerase I bind DNA to promote strand passage. Nucleic Acids Res 41:7462–7471. [PubMed][CrossRef]
25. DiNardo S, Voekel KA, Sternglanz R, Reynolds AE, Wright A. 1982. Escherichia coli DNA topoisomerase I mutants have compensatory mutations in DNA gyrase genes. Cell 31:43–51. [PubMed][CrossRef]
26. Pruss G, Manes SH, Drlica K. 1982. Escherichia coli DNA topoisomerase I mutants: increased supercoiling is corrected by mutations near gyrase genes. Cell 31:35–42. [CrossRef]
27. Richardson S, Higgins C, Lilley D. 1984. The genetic control of DNA supercoiling in Salmonella typhimurium. EMBO J 3:1745–1752. [PubMed]
28. Stupina VA, Wang JC. 2005. Viability of Escherichia coli topA mutants lacking DNA topoisomerase I. J Biol Chem 280:355–360. [PubMed][CrossRef]
29. Cheng B, Shukla S, Vasunilashorn S, Mukhopadhyay S, Tse-Dinh YC. 2005. Bacterial cell killing mediated by topoisomerase I DNA cleavage activity. J Biol Chem 280:38489–38495. [PubMed][CrossRef]
30. Tse-Dinh YC. 2009. Bacterial topoisomerase I as a target for discovery of antibacterial compounds. Nucleic Acids Res 37:731–737. [PubMed][CrossRef]
31. Tse-Dinh YC. 2007. Exploring DNA topoisomerases as targets of novel therapeutic agents in the treatment of infectious diseases. Infect Disord Drug Targets 7:3–9. [PubMed][CrossRef]
32. Cheng B, Liu IF, Tse-Dinh YC. 2007. Compounds with antibacterial activity that enhance DNA cleavage by bacterial DNA topoisomerase I. J Antimicrob Chemother 59:640–645. [PubMed][CrossRef]
33. Champoux JJ, Dulbecco R. 1972. An activity from mammalian cells that untwists superhelical DNA—a possible swivel for DNA replication (polyoma-ethidium bromide-mouse-embryo cells-dye binding assay). Proc Natl Acad Sci USA 69:143–146. [PubMed][CrossRef]
34. Stivers JT, Harris TK, Mildvan AS. 1997. Vaccinia DNA topoisomerase I: evidence supporting a free rotation mechanism for DNA supercoil relaxation. Biochemistry 36:5212–5222. [PubMed][CrossRef]
35. Stewart L, Redinbo MR, Qiu X, Hol WGJ, Champoux JJ. 1998. A model for the mechanism of human topoisomerase I. Science 279:1534–1540. [PubMed][CrossRef]
36. Pommier Y, Leo E, Zhang H, Marchand C. 2010. DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. Chem Biol 17:421–433. [PubMed][CrossRef]
37. DiGate RJ, Marians KJ. 1989. Molecular cloning and DNA sequence analysis of Escherichia coli topB, the gene encoding topoisomerase III. J Biol Chem 264:17924–17930. [PubMed]
38. DiGate RJ, Marians KJ. 1992. Escherichia coli topoisomerase III-catalyzed cleavage of RNA. J Biol Chem 267:20532–20535. [PubMed]
39. Mondragon A, DiGate R. 1999. The structure of Escherichia coli DNA topoisomerase III. Structure 7:1373–1383. [PubMed][CrossRef]
40. Lopez CR, Yang S, Deibler RW, Ray SA, Pennington JM, Digate RJ, Hastings PJ, Rosenberg SM, Zechiedrich EL. 2005. A role for topoisomerase III in a recombination pathway alternative to RuvABC. Mol Microbiol 58:80–101. [PubMed][CrossRef]
41. Li Z, Mondragon A, Hiasa H, Marians KJ, DiGate RJ. 2000. Identification of a unique domain essential for Escherichia coli DNA topoisomerase III-catalysed decatenation of replication intermediates. Mol Microbiol 35:888–895. [PubMed][CrossRef]
42. Perez-Cheeks BA, Lee C, Hayama R, Marians KJ. 2012. A role for topoisomerase III in Escherichia coli chromosome segregation. Mol Microbiol 86:1007–1022. [PubMed][CrossRef]
43. Gangloff S, McDonald JP, Bendixen C, Arthur L, Rothstein R. 1994. The yeast type I topoisomerase Top3 interacts with Sgs1, a DNA helicase homolog: a potential eukaryotic reverse gyrase. Mol Cell Biol 14:8391–8398. [PubMed]
44. Oakley TJ, Hickson ID. 2002. Defending genome integrity during S-phase: putative roles for RecQ helicases and topoisomerase III. DNA Repair (Amst) 1:175–207. [CrossRef]
45. Valenti A, De Felice M, Perugino G, Bizard A, Nadal M, Rossi M, Ciaramella M. 2012. Synergic and opposing activities of thermophilic RecQ-like helicase and topoisomerase 3 proteins in Holliday junction processing and replication fork stabilization. J Biol Chem 287:30282–30295. [PubMed][CrossRef]
46. Watt PM, Louis EJ, Borts RH, Hickson ID. 1995. Sgs1: a eukaryotic homolog of E. coli RecQ that interacts with topoisomerase II in vivo and is required for faithful chromosome segregation. Cell 81:253–260. [PubMed][CrossRef]
47. Suski C, Marians KJ. 2008. Resolution of converging replication forks by RecQ and topoisomerase III. Mol Cell 30:779–789. [PubMed][CrossRef]
48. Slesarev AI, Stetter KO, Lake JA, Gellert M, Krah R, Kozyavkin SA. 1993. DNA topoisomerase V is a relative of eukaryotic topoisomerase I from a hyperthermophilic prokaryote. Nature 364:735–737. [PubMed][CrossRef]
49. Rajan R, Taneja B, Mondragon A. 2010. Structures of minimal catalytic fragments of topoisomerase V reveals conformational changes relevant for DNA binding. Structure 18:829–838. [PubMed][CrossRef]
50. Taneja B, Patel A, Slesarev A, Mondragon A. 2006. Structure of the N-terminal fragment of topoisomerase V reveals a new family of topoisomerases. EMBO J 25:398–408. [PubMed][CrossRef]
51. Taneja B, Schnurr B, Slesarev A, Marko JF, Mondragon A. 2007. Topoisomerase V relaxes supercoiled DNA by a constrained swiveling mechanism. Proc Natl Acad Sci USA 104:14670–14675. [PubMed][CrossRef]
52. Koster DA, Croquette V, Dekker C, Shuman S, Dekker NH. 2005. Friction and torque govern the relaxation of DNA supercoils by eukaryotic topoisomerase IB. Nature 434:671–674. [PubMed][CrossRef]
53. Belova GI, Prasad R, Nazimov IV, Wilson SH, Slesarev AI. 2002. The domain organization and properties of individual domains of DNA topoisomerase V, a type 1B topoisomerase with DNA repair activities. J Biol Chem 277:4959–4965. [PubMed][CrossRef]
54. Forterre P. 2002. A hot story from comparative genomics: reverse gyrase is the only hyperthermophile-specific protein. Trends Genet 18:236–237. [PubMed][CrossRef]
55. Kikuchi A, Asai K. 1984. Reverse gyrase—a topoisomerase which introduces positive superhelical turns into DNA. Nature 309:677–681. [PubMed][CrossRef]
56. Forterre P, Mirambeau G, Jaxel C, Nadal M, Duguet M. 1985. High positive supercoiling in vitro catalyzed by an ATP and polyethylene glycol-stimulated topoisomerase from Sulfolobus acidocaldarius. EMBO J 4:2123–2128. [PubMed]
57. Shibata T, Nakasu S, Yasui K, Kikuchi A. 1987. Intrinsic DNA-dependent ATPase activity of reverse gyrase. J Biol Chem 262:10419–10421. [PubMed]
58. Confalonier F, Elie C, Nadal M, Bouthier de le Tour C, Forterre P, Duguet M. 1993. Reverse gyrase: a helicase-like domain and a type I topoisomerase in the same polypeptide. Proc Natl Acad Sci USA 90:4753–4757. [PubMed][CrossRef]
59. Rodriguez AC. 2002. Studies of a positive supercoiling machine. Nucleotide hydrolysis and a multifunctional “latch” in the mechanism of reverse gyrase. J Biol Chem 277:29865–29873. [PubMed][CrossRef]
60. del Toro Duany Y, Jungblut SP, Schmidt AS, Klostermeier D. 2008. The reverse gyrase helicase-like domain is a nucleotide-dependent switch that is attenuated by the topoisomerase domain. Nucleic Acids Res 36:5882–5895. [PubMed][CrossRef]
61. Declais AC, Marsault J, Confalonieri F, de La Tour CB, Duguet M. 2000. Reverse gyrase, the two domains intimately cooperate to promote positive supercoiling. J Biol Chem 275:19498–19504. [PubMed][CrossRef]
62. Ganguly A, del Toro Duany Y, Klostermeier D. 2013. Reverse gyrase transiently unwinds double-stranded DNA in an ATP-dependent reaction. J Mol Biol 425:32–40. [PubMed][CrossRef]
63. Rodriguez AC. 2003. Investigating the role of the latch in the positive supercoiling mechanism of reverse gyrase. Biochemistry 42:5993–6004. [PubMed][CrossRef]
64. Baldi MI, Benedetti P, Mattoccia E, Tocchini-Valentini GP. 1980. In vitro catenation and decatenation of DNA and a novel eucaryotic ATP-dependent topoisomerase. Cell 20:461–467. [PubMed][CrossRef]
65. Bauer DL, Marie R, Rasmussen KH, Kristensen A, Mir KU. 2012. DNA catenation maintains structure of human metaphase chromosomes. Nucleic Acids Res 40:11428–11434. [PubMed][CrossRef]
66. Hsieh T, Brutlag D. 1980. ATP-dependent DNA topoisomerase from D. melanogaster reversibly catenates duplex DNA rings. Cell 21:115–125. [PubMed][CrossRef]
67. Drake F, Hofmann G, Bartus H, Mattern M, Crooke S, Miracelli C. 1989. Biochemical and pharmacological properties of p170 and p180 forms of topoisomerase II. Biochemistry 28:8154–8160. [PubMed][CrossRef]
68. Capranico G, Tinelli S, Austin CA, Fisher ML, Zunino F. 1992. Different patterns of gene expression of topoisomerase II isoforms in differentiated tissues during murine development. Biochim Biophys Acta 1132:43–48. [PubMed][CrossRef]
69. Gonzalez RE, Lim CU, Cole K, Bianchini CH, Schools GP, Davis BE, Wada I, Roninson IB, Broude EV. 2011. Effects of conditional depletion of topoisomerase II on cell cycle progression in mammalian cells. Cell Cycle 10:3505–3514. [PubMed][CrossRef]
70. Turley H, Comley M, Houlbrook S, Nozaki N, Kikuchi A, Hickson ID, Gatter K, Harris AL. 1997. The distribution and expression of the two isoforms of DNA topoisomerase II in normal and neoplastic human tissues. Br J Cancer 75:1340–1346. [PubMed][CrossRef]
71. Vavrova A, Simunek T. 2012. DNA topoisomerase IIbeta: a player in regulation of gene expression and cell differentiation. Int J Biochem Cell Biol 44:834–837. [PubMed][CrossRef]
72. DiNardo S, Voelkel K, Sternglanz R. 1984. DNA topoisomerase II mutant of Saccharomyces cerevisiae: topoisomerase II is required for segregation of daughter molecules at the termination of DNA replication. Proc Natl Acad Sci USA 81:2616–2620. [PubMed][CrossRef]
73. Durrieu F, Samejima K, Fortune JM, Kandels-Lewis S, Osheroff N, Earnshaw WC. 2000. DNA topoisomerase IIalpha interacts with CAD nuclease and is involved in chromatin condensation during apoptotic execution. Curr Biol 10:923–926. [PubMed][CrossRef]
74. Caron PR. 1999. Appendix: compendium of DNA topoisomerase sequences. Methods Mol Biol 94:279–316. [PubMed][CrossRef]
75. Lynn R, Giaever G, Swanberg S, Wang JC. 1986. Tandem regions of yeast DNA topoisomerase II share homology with different subunits of bacterial gyrase. Science 233:647–648. [PubMed][CrossRef]
76. Watt PM, Hickson ID. 1994. Structure and function of type II DNA topoisomerases. Biochem J 303:681–695. [PubMed]
77. Schmidt BH, Osheroff N, Berger JM. 2012. Structure of a topoisomerase II-DNA-nucleotide complex reveals a new control mechanism for ATPase activity. Nat Struct Mol Biol 19:1147–1154. [PubMed][CrossRef]
78. Dong KC, Berger JM. 2007. Structural basis for gate-DNA recognition and bending by type IIA topoisomerases. Nature 450:1201–1205. [PubMed][CrossRef]
79. Classen S, Olland S, Berger JM. 2003. Structure of the topoisomerase II ATPase region and its mechanism of inhibition by the chemotherapeutic agent ICRF-187. Proc Natl Acad Sci USA 100:10629–10634. [PubMed][CrossRef]
80. Wigley DB, Davies GJ, Dodson EJ, Maxwell A, Dodson G. 1991. Crystal structure of an N-terminal fragment of the DNA gyrase B protein. Nature 351:624–629. [PubMed][CrossRef]
81. Berger JM, Gamblin SJ, Harrison SC, Wang JC. 1996. Structure and mechanism of DNA topoisomerase II. Nature 379:225–232. [PubMed][CrossRef]
82. Roca J, Berger JM, Harrison SC, Wang JC. 1996. DNA transport by a type II topoisomerase: direct evidence for a two-gate mechanism. Proc Natl Acad Sci USA 93:4057–4062. [PubMed][CrossRef]
83. Roca J, Wang JC. 1992. The capture of a DNA double helix by an ATP-dependent protein clamp: a key step in DNA transport by type II DNA topoisomerases. Cell 71:833–840. [PubMed][CrossRef]
84. Roca J, Wang JC. 1994. DNA transport by a type II DNA topoisomerase: evidence in favor of a two-gate mechanism. Cell 77:609–616. [PubMed][CrossRef]
85. Bergerat A, de Massy B, Gadelle D, Varoutas PC, Nicolas A, Forterre P. 1997. An atypical topoisomerase II from Archaea with implications for meiotic recombination. Nature 386:414–417. [PubMed][CrossRef]
86. Bergerat A, Gadelle D, Forterre P. 1994. Purification of a DNA topoisomerase II from the hyperthermophilic archaeon Sulfolobus shibatae. A thermostable enzyme with both bacterial and eucaryal features. J Biol Chem 269:27663–27669. [PubMed]
87. Hartung F, Puchta H. 2000. Molecular characterisation of two paralogous SPO11 homologues in Arabidopsis thaliana. Nucleic Acids Res 28:1548–1554. [PubMed][CrossRef]
88. Aravind L, Iyer LM, Wellems TE, Miller LH. 2003. Plasmodium biology: genomic gleanings. Cell 115:771–785. [PubMed][CrossRef]
89. Hartung F, Angelis KJ, Meister A, Schubert I, Melzer M, Puchta H. 2002. An archaebacterial topoisomerase homolog not present in other eukaryotes is indispensable for cell proliferation of plants. Curr Biol 12:1787–1791. [CrossRef]
90. Aravind L, Leipe DD, Koonin EV. 1998. Toprim—a conserved catalytic domain in type IA and II topoisomerases, DnaG-type primases, OLD family nucleases and RecR proteins. Nucleic Acids Res 26:4205–4213. [PubMed][CrossRef]
91. Corbett KD, Berger JM. 2003. Structure of the topoisomerase VI-B subunit: implications for type II topoisomerase mechanism and evolution. EMBO J 22:151–163. [PubMed][CrossRef]
92. Nichols MD, DeAngelis K, Keck JL, Berger JM. 1999. Structure and function of an archaeal topoisomerase VI subunit with homology to the meiotic recombination factor Spo 11. EMBO J 18:6177–6188. [PubMed][CrossRef]
93. Corbett KD, Berger JM. 2005. Structural dissection of ATP turnover in the prototypical GHL ATPase TopoVI. Structure 13:873–882. [PubMed][CrossRef]
94. Corbett KD, Benedetti P, Berger JM. 2007. Holoenzyme assembly and ATP-mediated conformational dynamics of topoisomerase VI. Nat Struct Mol Biol 14:611–619. [PubMed][CrossRef]
95. Graille M, Cladiere L, Durand D, Lecointe F, Gadelle D, Quevillon-Cheruel S, Vachette P, Forterre P, van Tilbeurgh H. 2008. Crystal structure of an intact type II DNA topoisomerase: insights into DNA transfer mechanisms. Structure 16:360–370. [PubMed][CrossRef]
96. Buhler C, Lebbink JH, Bocs C, Ladenstein R, Forterre P. 2001. DNA topoisomerase VI generates ATP-dependent double-strand breaks with two-nucleotide overhangs. J Biol Chem 276:37215–37222. [PubMed][CrossRef]
97. Corbett KD, Berger JM. 2003. Emerging roles for plant topoisomerase VI. Chem Biol 10:107–111. [PubMed][CrossRef]
98. Gadelle D, Krupovic M, Raymann K, Mayer C, Forterre P. 2014. DNA topoisomerase VIII: a novel subfamily of type IIB topoisomerases encoded by free or integrated plasmids in Archaea and Bacteria. Nucleic Acids Res 42:8578–8591. [PubMed][CrossRef]
99. Peng H, Marians KJ. 1993. Escherichia coli topoisomerase IV. J Biol Chem 268:24481–24490. [PubMed]
100. Levine C, Hiasa H, Marians KJ. 1998. DNA gyrase and topoisomerase IV: biochemical activities, physiological roles during chromosome replication, and drug sensitivities. Biochim Biophys Acta 1400:29–43. [PubMed][CrossRef]
101. Crisona NJ, Strick TR, Bensimon D, Croquette V, Cozzarelli NR. 2000. Preferential relaxation of positively supercoiled DNA by E. coli topoisomerase IV in single-molecule and ensemble measurements. Genes Dev 14:2881–2892. [PubMed][CrossRef]
102. Deibler RW, Rahmati S, Zechiedrich EL. 2001. Topoisomerase IV, alone, unknots DNA in E. coli. Genes Dev 15:748–761. [PubMed][CrossRef]
103. Lopez V, Martinez-Robles ML, Hernandez P, Krimer DB, Schvartzman JB. 2012. Topo IV is the topoisomerase that knots and unknots sister duplexes during DNA replication. Nucleic Acids Res 40:3563–3573. [PubMed][CrossRef]
104. Baba T, Kuwahara-Arai K, Uchiyama I, Takeuchi F, Ito T, Hiramatsu K. 2009. Complete genome sequence of Macrococcus caseolyticus strain JCSCS5402, [corrected] reflecting the ancestral genome of the human-pathogenic staphylococci. J Bacteriol 191:1180–1190. [PubMed][CrossRef]
105. Ferrero L, Cameron B, Manse B, Lagneaux D, Crouzet J, Famechon A, Blanche F. 1994. Cloning and primary structure of Staphylococcus aureus DNA topoisomerase IV: a primary target of fluoroquinolones. Mol Microbiol 13:641–653. [PubMed][CrossRef]
106. Takami H, Takaki Y, Uchiyama I. 2002. Genome sequence of Oceanobacillus iheyensis isolated from the Iheya Ridge and its unexpected adaptive capabilities to extreme environments. Nucleic Acids Res 30:3927–3935. [PubMed][CrossRef]
107. Peng H, Marians KJ. 1995. The interaction of Escherichia coli topoisomerase IV with DNA. J Biol Chem 270:25286–25290. [PubMed][CrossRef]
108. Ullsperger C, Cozzarelli NR. 1996. Contrasting enzymatic activities of topoisomerase IV and DNA gyrase from Escherichia coli. J Biol Chem 271:31549–31555. [PubMed][CrossRef]
109. Neuman KC, Charvin G, Bensimon D, Croquette V. 2009. Mechanisms of chiral discrimination by topoisomerase IV. Proc Natl Acad Sci USA 106:6986–6991. [PubMed][CrossRef]
110. Stone MD, Bryant Z, Crisona NJ, Smith SB, Vologodskii A, Bustamante C, Cozzarelli NR. 2003. Chirality sensing by Escherichia coli topoisomerase IV and the mechanism of type II topoisomerases. Proc Natl Acad Sci USA 100:8654–8659. [PubMed][CrossRef]
111. Timsit Y. 2011. Local sensing of global DNA topology: from crossover geometry to type II topoisomerase processivity. Nucleic Acids Res 39:8665–8676. [PubMed][CrossRef]
112. Zechiedrich EL, Khodursky AB, Cozzarelli NR. 1997. Topoisomerase IV, not gyrase, decatenates products of site-specific recombination in Escherichia coli. Genes Dev 11:2580–2592. [PubMed][CrossRef]
113. Adams DE, Shekhtman EM, Zechiedrich EL, Schmid MB, Cozzarelli NR. 1992. The role of topoisomerase IV in partitioning bacterial replicons and the structure of catenated intermediates in DNA replication. Cell 71:277–288. [PubMed][CrossRef]
114. Bellon S, Parsons JD, Wei Y, Hayakawa K, Swenson LL, Charifson PS, Lippke JA, Aldape R, Gross CH. 2004. 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. Antimicrob Agents Chemother 48:1856–1864. [PubMed][CrossRef]
115. Corbett KD, Schoeffler AJ, Thomsen ND, Berger JM. 2005. The structural basis for substrate specificity in DNA topoisomerase IV. J Mol Biol 351:545–561. [PubMed][CrossRef]
116. Hsieh TJ, Farh L, Huang WM, Chan NL. 2004. Structure of the topoisomerase IV C-terminal domain: a broken beta-propeller implies a role as geometry facilitator in catalysis. J Biol Chem 279:55587–55593. [PubMed][CrossRef]
117. Fass D, Bogden CE, Berger JM. 1999. Quaternary changes in topoisomerase II may direct orthogonal movements of two DNA strands. Nat Struct Biol 6:322–326. [PubMed][CrossRef]
118. Morais Cabral JH, Jackson AP, Smith CV, Shikotra N, Maxwell A, Liddington RC. 1997. Crystal structure of the breakage-reunion domain of DNA gyrase. Nature 388:903–906. [PubMed][CrossRef]
119. Corbett KD, Shultzaberger RK, Berger JM. 2004. The C-terminal domain of DNA gyrase A adopts a DNA-bending β-pinwheel fold. Proc Natl Acad Sci USA 101:7293–7298. [PubMed][CrossRef]
120. Costenaro L, Grossmann JG, Ebel C, Maxwell A. 2005. Small-angle X-ray scattering reveals the solution structure of the full-length DNA gyrase A subunit. Structure 13:287–296. [PubMed][CrossRef]
121. Kampranis SC, Maxwell A. 1996. Conversion of DNA gyrase into a conventional type II topoisomerase. Proc Natl Acad Sci USA 93:14416–14421. [PubMed][CrossRef]
122. Laponogov I, Veselkov DA, Crevel IM, Pan XS, Fisher LM, Sanderson MR. 2013. Structure of an ‘open’ clamp type II topoisomerase-DNA complex provides a mechanism for DNA capture and transport. Nucleic Acids Res 41:9911–9923. [PubMed][CrossRef]
123. Gellert M, Mizuuchi K, O’Dea MH, Nash HA. 1976. DNA gyrase: an enzyme that introduces superhelical turns into DNA. Proc Natl Acad Sci USA 73:3872–3876. [PubMed][CrossRef]
124. Gellert M, O’Dea MH, Itoh T, Tomizawa J. 1976. Novobiocin and coumermycin inhibit DNA supercoiling catalyzed by DNA gyrase. Proc Natl Acad Sci USA 73:4474–4478. [PubMed][CrossRef]
125. Sugino A, Higgins NP, Brown PO, Peebles CL, Cozzarelli NR. 1978. Energy coupling in DNA gyrase and the mechanism of action of novobiocin. Proc Natl Acad Sci USA 75:4838–4842. [PubMed][CrossRef]
126. Kreuzer KN, Cozzarelli NR. 1980. Formation and resolution of DNA catenanes by DNA gyrase. Cell 20:245–254. [PubMed][CrossRef]
127. Marians KJ. 1987. DNA gyrase-catalyzed decatenation of multiply linked DNA dimers. J Biol Chem 21:10362–10368. [PubMed]
128. Mizuuchi K, Fisher M, O’Dea M, Gellert M. 1980. DNA gyrase action involves the introduction of transient double-strand breaks into DNA. Proc Natl Acad Sci USA 77:1847–1851. [PubMed][CrossRef]
129. Gellert M, Fisher LM, O’Dea MH. 1979. DNA gyrase: purification and catalytic properties of a fragment of gyrase B protein. Proc Natl Acad Sci USA 76:6289–6293. [PubMed][CrossRef]
130. Higgins NP, Peebles CL, Sugino A, Cozzarelli NR. 1978. Purification of subunits of Escherichia coli DNA gyrase and reconstitution of enzymatic activity. Proc Natl Acad Sci USA 75:1773–1777. [PubMed][CrossRef]
131. Adachi T, Mizuuchi M, Robinson EA, Appella E, O’Dea MH, Gellert M, Mizuuchi K. 1987. DNA sequence of the E. coli gyrB gene: application of a new sequencing strategy. Nucleic Acids Res 15:771–784. [PubMed][CrossRef]
132. Klevan L, Wang JC. 1980. Deoxyribonucleic acid gyrase-deoxyribonucleic acid complex containing 140 base pairs of deoxyribonuclease acid and an α2β2 protein core. Biochemistry 19:5229–5234. [PubMed][CrossRef]
133. Sugino A, Higgins NP, Cozzarelli NR. 1980. DNA gyrase subunit stoichiometry and the covalent attachment of subunit A to DNA during DNA cleavage. Nucleic Acids Res 8:3865–3874. [PubMed][CrossRef]
134. Swanberg SL, Wang JC. 1987. Cloning and sequencing of the Escherichia coli gyrA gene coding for the A subunit of DNA gyrase. J Mol Biol 197:729–736. [PubMed][CrossRef]
135. Cho HS, Lee SS, Kim KD, Hwang I, Lim JS, Park YI, Pai HS. 2004. DNA gyrase is involved in chloroplast nucleoid partitioning. Plant Cell 16:2665–2682. [PubMed][CrossRef]
136. Wall MK, Mitchenall LA, Maxwell A. 2004. Arabidopsis thaliana DNA gyrase is targeted to chloroplasts and mitochondria. Proc Natl Acad Sci USA 101:7821–7826. [PubMed][CrossRef]
137. Carucci DJ, Gardner MJ, Tettelin H, Cummings LM, Smith HO, Adams MD, Hoffman SL, Venter JC. 1998. The malaria genome sequencing project. Expert Rev Mol Med 1998:1–9. [PubMed][CrossRef]
138. Dar MA, Sharma A, Mondal N, Dhar SK. 2007. Molecular cloning of apicoplast-targeted Plasmodium falciparum DNA gyrase genes: unique intrinsic ATPase activity and ATP-independent dimerization of PfGyrB subunit. Eukaryot Cell 6:398–412. [PubMed][CrossRef]
139. Kampranis SC, Maxwell A. 1998. Conformational changes in DNA gyrase revealed by limited proteolysis. J Biol Chem 273:22606–22614. [PubMed][CrossRef]
140. Reece RJ, Maxwell A. 1989. Tryptic fragments of the Escherichia coli DNA gyrase A protein. J Biol Chem 264:19648–19653. [PubMed]
141. Brown PO, Peebles CL, Cozzarelli NR. 1979. A topoisomerase from Escherichia coli related to DNA gyrase. Proc Natl Acad Sci USA 76:6110–6114. [PubMed][CrossRef]
142. Chatterji M, Unniram S, Maxwell A, Nagaraja V. 2000. The additional 165 amino acids in the B protein of Escherichia coli DNA gyrase have an important role in DNA binding. J Biol Chem 275:22888–22894. [PubMed][CrossRef]
143. Noble CG, Maxwell A. 2002. The role of GyrB in the DNA cleavage-religation reaction of DNA gyrase: a proposed two-metal-ion mechanism. J Mol Biol 318:361–371. [PubMed][CrossRef]
144. Schoeffler AJ, May AP, Berger JM. 2010. A domain insertion in Escherichia coli GyrB adopts a novel fold that plays a critical role in gyrase function. Nucleic Acids Res 38:7830–7844. [PubMed][CrossRef]
145. Costenaro L, Grossmann JG, Ebel C, Maxwell A. 2007. Modular structure of the full-length DNA gyrase B subunit revealed by small-angle X-ray scattering. Structure 15:329–339. [PubMed][CrossRef]
146. Fu G, Wu J, Liu W, Zhu D, Hu Y, Deng J, Zhang XE, Bi L, Wang DC. 2009. Crystal structure of DNA gyrase B’ domain sheds lights on the mechanism for T-segment navigation. Nucleic Acids Res 37:5908–5916. [PubMed][CrossRef]
147. Horowitz DS, Wang JC. 1987. Mapping the active site tyrosine of Escherichia coli DNA gyrase. J Biol Chem 262:5339–5344. [PubMed]
148. Schoeffler AJ, Berger JM. 2008. DNA topoisomerases: harnessing and constraining energy to govern chromosome topology. Q Rev Biophys 41:41–101. [PubMed][CrossRef]
149. Reece RJ, Maxwell A. 1991. The C-terminal domain of the Escherichia coli DNA gyrase A subunit is a DNA-binding protein. Nucleic Acids Res 19:1399–1405. [PubMed][CrossRef]
150. Neuman KC. 2010. Evolutionary twist on topoisomerases: conversion of gyrase to topoisomerase IV. Proc Natl Acad Sci USA 107:22363–22364. [PubMed][CrossRef]
151. Tingey AP, Maxwell A. 1996. Probing the role of the ATP-operated clamp in the strand-passage reaction of DNA gyrase. Nucleic Acids Res 24:4868–4873. [PubMed][CrossRef]
152. Dutta R, Inouye M. 2000. GHKL, an emergent ATPase/kinase superfamily. Trends Biochem Sci 25:24–28. [PubMed][CrossRef]
153. Smith CV, Maxwell A. 1998. Identification of a residue involved in transition-state stabilization in the ATPase reaction of DNA gyrase. Biochemistry 37:9658–9667. [PubMed][CrossRef]
154. Piton J, Petrella S, Delarue M, Andre-Leroux G, Jarlier V, Aubry A, Mayer C. 2010. Structural insights into the quinolone resistance mechanism of Mycobacterium tuberculosis DNA gyrase. PLoS ONE 5:e12245. [PubMed][CrossRef]
155. Hsieh TJ, Yen TJ, Lin TS, Chang HT, Huang SY, Hsu CH, Farh L, Chan NL. 2010. Twisting of the DNA-binding surface by a beta-strand-bearing proline modulates DNA gyrase activity. Nucleic Acids Res 38:4173–4181. [PubMed][CrossRef]
156. Ruthenburg AJ, Graybosch DM, Huetsch JC, Verdine GL. 2005. A superhelical spiral in the Escherichia coli DNA gyrase A C-terminal domain imparts unidirectional supercoiling bias. J Biol Chem 280:26177–26184. [PubMed][CrossRef]
157. Tretter EM, Berger JM. 2012. 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 287:18645–18654. [PubMed][CrossRef]
158. Kramlinger VM, Hiasa H. 2006. The “GyrA-box” is required for the ability of DNA gyrase to wrap DNA and catalyze the supercoiling reaction. J Biol Chem 281:3738–3742. [PubMed][CrossRef]
159. Ward D, Newton A. 1997. Requirement of topoisomerase IV parC and parE genes for cell cycle progression and developmental regulation in Caulobacter crescentus. Mol Microbiol 26:897–910. [PubMed][CrossRef]
160. Lanz MA, Klostermeier D. 2012. The GyrA-box determines the geometry of DNA bound to gyrase and couples DNA binding to the nucleotide cycle. Nucleic Acids Res 40:10893–10903. [PubMed][CrossRef]
161. Baker NM, Weigand S, Maar-Mathias S, Mondragon A. 2011. Solution structures of DNA-bound gyrase. Nucleic Acids Res 39:755–766. [PubMed][CrossRef]
162. Papillon J, Menetret JF, Batisse C, Helye R, Schultz P, Potier N, Lamour V. 2013. Structural insight into negative DNA supercoiling by DNA gyrase, a bacterial type 2A DNA topoisomerase. Nucleic Acids Res 41:7815–7827. [PubMed][CrossRef]
163. Wohlkonig A, Chan PF, Fosberry AP, Homes P, Huang J, Kranz M, Leydon VR, Miles TJ, Pearson ND, Perera RL, Shillings AJ, Gwynn MN, Bax BD. 2010. Structural basis of quinolone inhibition of type IIA topoisomerases and target-mediated resistance. Nat Struct Mol Biol 17:1152–1153. [PubMed][CrossRef]
164. Bax BD, Chan PF, Eggleston DS, Fosberry A, Gentry DR, Gorrec F, Giordano I, Hann MM, Hennessy A, Hibbs M, Huang J, Jones E, Jones J, Brown KK, Lewis CJ, May EW, Saunders MR, Singh O, Spitzfaden CE, Shen C, Shillings A, Theobald AJ, Wohlkonig A, Pearson ND, Gwynn MN. 2010. Type IIA topoisomerase inhibition by a new class of antibacterial agents. Nature 466:935–940. [PubMed][CrossRef]
165. Laponogov I, Sohi MK, Veselkov DA, Pan X-S, Sawhney R, Thompson AW, McAuley KE, Fisher LM, Sanderson MR. 2009. Structural insight into the quinolone-DNA cleavage complex of type IIA topoisomerases. Nat Struct Mol Biol 16:667–669. [PubMed][CrossRef]
166. Heddle JG, Mitelheiser S, Maxwell A, Thomson NH. 2004. Nucleotide binding to DNA gyrase causes loss of DNA wrap. J Mol Biol 337:597–610. [PubMed][CrossRef]
167. Lanz MA, Klostermeier D. 2011. Guiding strand passage: DNA-induced movement of the gyrase C-terminal domains defines an early step in the supercoiling cycle. Nucleic Acids Res 39:9681–9694. [PubMed][CrossRef]
168. Fisher LM, Mizuuchi K, O’Dea MH, Ohmori H, Gellert M. 1981. Site-specific interaction of DNA gyrase with DNA. Proc Natl Acad Sci USA 78:4165–4169. [PubMed][CrossRef]
169. Kirkegaard K, Wang JC. 1981. Mapping the topography of DNA wrapped around gyrase by nucleolytic and chemical probing of complexes of unique DNA sequences. Cell 23:721–729. [PubMed][CrossRef]
170. Liu L, Wang J. 1978. Micrococcus luteus DNA gyrase: active components and a model for its supercoiling of DNA. Proc Natl Acad Sci USA 75:2098–2102. [PubMed][CrossRef]
171. Morrison A, Cozzarelli NR. 1981. Contacts between DNA gyrase and its binding site on DNA: features of symmetry and asymmetry revealed by protection from nucleases. Proc Natl Acad Sci USA 78:1416–1420. [PubMed][CrossRef]
172. Orphanides G, Maxwell A. 1994. Evidence for a conformational change in the DNA gyrase-DNA complex from hydroxyl radical footprinting. Nucleic Acids Res 22:1567–1575. [PubMed][CrossRef]
173. Gubaev A, Klostermeier D. 2011. DNA-induced narrowing of the gyrase N-gate coordinates T-segment capture and strand passage. Proc Natl Acad Sci USA 108:14085–14090. [PubMed][CrossRef]
174. Basu A, Schoeffler AJ, Berger JM, Bryant Z. 2012. ATP binding controls distinct structural transitions of Escherichia coli DNA gyrase in complex with DNA. Nat Struct Mol Biol 19:538–546. [PubMed][CrossRef]
175. Kampranis SC, Bates AD, Maxwell A. 1999. A model for the mechanism of strand passage by DNA gyrase. Proc Natl Acad Sci USA 96:8414–8419. [PubMed][CrossRef]
176. Tretter EM, Berger JM. 2012. 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 287:18636–18644. [PubMed][CrossRef]
177. Wang JC. 1998. Moving one DNA double helix through another by a type II DNA topoisomerase: the story of a simple molecular machine. Q Rev Biophys 31:107–144. [PubMed][CrossRef]
178. Ali JA, Jackson AP, Howells AJ, Maxwell A. 1993. The 43-kDa N-terminal fragment of the gyrase B protein hydrolyses ATP and binds coumarin drugs. Biochemistry 32:2717–2724. [PubMed][CrossRef]
179. Ali JA, Orphanides G, Maxwell A. 1995. Nucleotide binding to the 43-kilodalton N-terminal fragment of the DNA gyrase B protein. Biochemistry 34:9801–9808. [PubMed][CrossRef]
180. Lindsley JE, Wang JC. 1993. On the coupling between ATP usage and DNA transport by yeast DNA topoisomerase II. J Biol Chem 268:8096–8104. [PubMed]
181. Peebles CL, Higgins NP, Kreuzer KN, Morrison A, Brown PO, Sugino A, Cozzarelli NR. 1978. Structure and activities of Escherichia coli DNA gyrase. Cold Spring Harbor Symp Quant Biol 43:41–52. [CrossRef]
182. Tamura JK, Bates AD, Gellert M. 1992. Slow interaction of 5′-adenylyl-β,γ-imidodiphosphate with Escherichia coli DNA gyrase. J Biol Chem 267:9214–9222. [PubMed]
183. Bates AD, O’Dea MH, Gellert M. 1996. Energy coupling in Escherichia coli DNA gyrase: the relationship between nucleotide binding, strand passage, and DNA supercoiling. Biochemistry 35:1408–1416. [PubMed][CrossRef]
184. Williams NL, Maxwell A. 1999. Locking the DNA gate of DNA gyrase: investigating the effects on DNA cleavage and ATP hydrolysis. Biochemistry 38:14157–14164. [PubMed][CrossRef]
185. Baird CL, Gordon MS, Andrenyak DM, Marecek JF, Lindsley JE. 2001. The ATPase reaction cycle of yeast DNA topoisomerase II. Slow rates of ATP resynthesis and P(i) release. J Biol Chem 276:27893–27898. [PubMed][CrossRef]
186. Baird CL, Harkins TT, Morris SK, Lindsley JE. 1999. Topoisomerase II drives DNA transport by hydrolyzing one ATP. Proc Natl Acad Sci USA 96:13685–13690. [PubMed][CrossRef]
187. Kampranis SC, Maxwell A. 1998. Hydrolysis of one ATP is sufficient to promote supercoiling by DNA gyrase. J Biol Chem 273:26305–26309. [PubMed][CrossRef]
188. Williams NL, Maxwell A. 1999. Probing the two-gate mechanism of DNA gyrase using cysteine cross-linking. Biochemistry 38:13502–13511. [PubMed][CrossRef]
189. Bansal S, Sinha D, Singh M, Cheng B, Tse-Dinh YC, Tandon V. 2012. 3,4-Dimethoxyphenyl bis-benzimidazole, a novel DNA topoisomerase inhibitor that preferentially targets Escherichia coli topoisomerase I. J Antimicrob Chemother 67:2882–2891. [PubMed][CrossRef]
190. Collin F, Karkare S, Maxwell A. 2011. Exploiting bacterial DNA gyrase as a drug target: current state and perspectives. Appl Microbiol Biotechnol 92:479–497. [PubMed][CrossRef]
191. Heide L. 2009. The aminocoumarins: biosynthesis and biology. Nat Prod Rep 26:1241–1250. [PubMed][CrossRef]
192. Hinman JW, Caron EL, Hoeksema H. 1957. The structure of novobiocin. J Am Chem Soc 79:3789–3800. [CrossRef]
193. Hoeksema H, Johnson JL, Hinman JW. 1955. Structural studies on Streptonivicin, a new antibiotic. J Am Chem Soc 77:6710–6711. [CrossRef]
194. Ninet L, Preudhomme J, Dubost M, Charpent Y, Chezelle N, Cartier M, Benazet F, Abraham A, Theilleu J, Threlfal T, Wright DE, Vuillemi B, Mancy D, Florent J, Godard C. 1972. Clorobiocin (18.631 R.P), a new chlorinated antibiotic produced by several Streptomyces species. Acad Sci Ser C 275:455–458.
195. Ryan MJ. 1976. Coumermycin A1: a preferential inhibitor of replicative DNA synthesis in Escherichia coli. I. In vivo characterization. Biochemistry 15:3769–3777. [PubMed][CrossRef]
196. Ryan MJ, Wells RD. 1976. Coumermycin A1: a preferential inhibitor of replicative DNA synthesis in Escherichia coli. II. In vitro characterization. Biochemistry 15:3778–3782. [PubMed][CrossRef]
197. Staudenbauer W. 1975. Novobiocin—a specific inhibitor of semiconservative DNA replication in permeabilized Escherichia coli cells. J Mol Biol 96:201–205. [PubMed][CrossRef]
198. Gellert M, Mizuuchi K, O’Dea MH, Itoh T, Tomizawa J. 1977. Nalidixic acid resistance: a second genetic character involved in DNA gyrase activity. Proc Natl Acad Sci USA 74:4772–4776. [PubMed][CrossRef]
199. Sugino A, Peebles CL, Kruezer KN, Cozzarelli NR. 1977. Mechanism of action of nalidixic acid: purification of Escherichia coli nalA gene product and its relationship to DNA gyrase and a novel nicking-closing enzyme. Proc Natl Acad Sci USA 74:4767–4771. [PubMed][CrossRef]
200. Mizuuchi K, O’Dea MH, Gellert M. 1978. DNA gyrase: subunit structure and ATPase activity of the purified enzyme. Proc Natl Acad Sci USA 75:5960–5963. [PubMed][CrossRef]
201. Contreras A, Maxwell A. 1992. gyrB mutations which confer coumarin resistance also affect DNA supercoiling and ATP hydrolysis by Escherichia coli DNA gyrase. Mol Microbiol 6:1617–1624. [PubMed][CrossRef]
202. del Castillo I, Vizan J, Rodriguez-Sainz M, Moreno F. 1991. An unusual mechanism for resistance to the antibiotic coumermycin A1. Proc Natl Acad Sci USA 88:8860–8864. [PubMed][CrossRef]
203. Holdgate GA, Tunnicliffe A, Ward WHJ, Weston SA, Rosenbrock G, Barth PT, Taylor IWF, Pauptit RA, Timms D. 1997. 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. Biochemistry 36:9663–9673. [PubMed][CrossRef]
204. Lewis RJ, Singh OM, Smith CV, Skarzynski T, Maxwell A, Wonacott AJ, Wigley DB. 1996. The nature of inhibition of DNA gyrase by the coumarins and the cyclothialidines revealed by X-ray crystallography. EMBO J 15:1412–1420. [PubMed]
205. Tsai FT, Singh OM, Skarzynski T, Wonacott AJ, Weston S, Tucker A, Pauptit RA, Breeze AL, Poyser JP, O’Brien R, Ladbury JE, Wigley DB. 1997. 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. Proteins 28:41–52. [CrossRef]
206. Hardy CD, Cozzarelli NR. 2003. Alteration of Escherichia coli topoisomerase IV to novobiocin resistance. Antimicrob Agents Chemother 47:941–947. [CrossRef]
207. Li SM, Heide L. 2006. The biosynthetic gene clusters of aminocoumarin antibiotics. Planta Med 72:1093–1099. [PubMed][CrossRef]
208. Pojer F, Li SM, Heide L. 2002. Molecular cloning and sequence analysis of the clorobiocin biosynthetic gene cluster: new insights into the biosynthesis of aminocoumarin antibiotics. Microbiology 148:3901–3911. [PubMed]
209. Steffensky M, Muhlenweg A, Wang ZX, Li SM, Heide L. 2000. Identification of the novobiocin biosynthetic gene cluster of Streptomyces spheroides NCIB 11891. Antimicrob Agents Chemother 44:1214–1222. [PubMed][CrossRef]
210. Wang ZX, Li SM, Heide L. 2000. Identification of the coumermycin A(1) biosynthetic gene cluster of Streptomyces rishiriensis DSM 40489. Antimicrob Agents Chemother 44:3040–3048. [PubMed][CrossRef]
211. Eustaquio AS, Gust B, Luft T, Li SM, Chater KF, Heide L. 2003. Clorobiocin biosynthesis in Streptomyces. Identification of the halogenase and generation of structural analogs. Chem Biol 10:279–288. [PubMed][CrossRef]
212. Anderle C, Stieger M, Burrell M, Reinelt S, Maxwell A, Page M, Heide L. 2008. Biological activities of novel gyrase inhibitors of the aminocoumarin class. Antimicrob Agents Chemother 52:1982–1990. [PubMed][CrossRef]
213. Flatman RH, Eustaquio A, Li SM, Heide L, Maxwell A. 2006. Structure-activity relationships of aminocoumarin-type gyrase and topoisomerase IV inhibitors obtained by combinatorial biosynthesis. Antimicrob Agents Chemother 50:1136–1142. [PubMed][CrossRef]
214. Holzenkampfer M, Walker M, Zeeck A, Schimana J, Fiedler HP. 2002. Simocyclinones, novel cytostatic angucyclinone antibiotics produced by Streptomyces antibioticus Tu 6040. II. Structure elucidation and biosynthesis. J Antibiot (Tokyo) 55:301–307. [PubMed][CrossRef]
215. Schimana J, Fiedler HP, Groth I, Sussmuth R, Beil W, Walker M, Zeeck A. 2000. Simocyclinones, novel cytostatic angucyclinone antibiotics produced by Streptomyces antibioticus Tu 6040. I. Taxonomy, fermentation, isolation and biological activities. J Antibiot (Tokyo) 53:779–787. [PubMed][CrossRef]
216. Galm U, Schimana J, Fiedler HP, Schmidt J, Li SM, Heide L. 2002. Cloning and analysis of the simocyclinone biosynthetic gene cluster of Streptomyces antibioticus Tu 6040. Arch Microbiol 178:102–114. [PubMed][CrossRef]
217. Trefzer A, Pelzer S, Schimana J, Stockert S, Bihlmaier C, Fiedler HP, Welzel K, Vente A, Bechthold A. 2002. Biosynthetic gene cluster of simocyclinone, a natural multihybrid antibiotic. Antimicrob Agents Chemother 46:1174–1182. [PubMed][CrossRef]
218. Flatman RH, Howells AJ, Heide L, Fiedler H-P, Maxwell A. 2005. Simocyclinone D8: an inhibitor of DNA gyrase with a novel mode of action. Antimicrob Agents Chemother 49:1093–1100. [PubMed][CrossRef]
219. Edwards MJ, Flatman RH, Mitchenall LA, Stevenson CE, Le TBK, Fiedler HP, McKay AR, Clarke TA, Buttner MJ, Lawson DM, Maxwell A. 2009. A crystal structure of the bifunctional antibiotic, simocyclinone D8, bound to DNA gyrase. Science 326:1415–1418. [PubMed][CrossRef]
220. Edwards MJ, Williams MA, Maxwell A, McKay AR. 2011. Mass spectrometry reveals that the antibiotic simocyclinone D8 binds to DNA gyrase in a “bent-over” conformation: evidence of positive cooperativity in binding. Biochemistry 50:3432–3440. [PubMed][CrossRef]
221. Hearnshaw SJ, Edwards MJ, Stevenson CE, Lawson DM, Maxwell A. 2014. A new crystal structure of the bifunctional antibiotic simocyclinone d8 bound to DNA gyrase gives fresh insight into the mechanism of inhibition. J Mol Biol 426:2023–2033. [PubMed][CrossRef]
222. Richter SN, Frasson I, Palumbo M, Sissi C, Palu G. 2010. Simocyclinone D8 turns on against Gram-negative bacteria in a clinical setting. Bioorg Med Chem Lett 20:1202–1204. [PubMed][CrossRef]
223. Sadiq AA, Patel MR, Jacobson BA, Escobedo M, Ellis K, Oppegard LM, Hiasa H, Kratzke RA. 2010. Anti-proliferative effects of simocyclinone D8 (SD8), a novel catalytic inhibitor of topoisomerase II. Invest New Drugs 28:20–25. [PubMed][CrossRef]
224. Drlica K, Malik M. 2003. Fluoroquinolones: action and resistance. Curr Top Med Chem 3:249–282. [PubMed][CrossRef]
225. Emmerson AM, Jones AM. 2003. The quinolones: decades of development and use. J Antimicrob Chemother 51(Suppl 1):13–20. [PubMed][CrossRef]
226. Van Bambeke F, Michot JM, Van Eldere J, Tulkens PM. 2005. Quinolones in 2005: an update. Clin Microbiol Infect 11:256–280. [PubMed][CrossRef]
227. King DE, Malone R, Lilley SH. 2000. New classification and update on the quinolone antibiotics. Am Fam Physician 61:2741–2748. [PubMed]
228. Hiasa H, Yousef DO, Marians KJ. 1996. DNA strand cleavage is required for replication fork arrest by a frozen topoisomerase-quinolone-DNA ternary complex. J Biol Chem 271:26424–26429. [PubMed][CrossRef]
229. Wentzell LM, Maxwell A. 2000. The complex of DNA gyrase and quinolone drugs on DNA forms a barrier to the T7 DNA polymerase replication complex. J Mol Biol 304:779–791. [PubMed][CrossRef]
230. Willmott CJR, Critchlow SE, Eperon IC, Maxwell A. 1994. The complex of DNA gyrase and quinolone drugs with DNA forms a barrier to transcription by RNA polymerase. J Mol Biol 242:351–363. [PubMed][CrossRef]
231. Drlica K, Malik M, Kerns RJ, Zhao X. 2008. Quinolone-mediated bacterial death. Antimicrob Agents Chemother 52:385–392. [PubMed][CrossRef]
232. Malik M, Hussain S, Drlica K. 2007. Effect of anaerobic growth on quinolone lethality with Escherichia coli. Antimicrob Agents Chemother 51:28–34. [PubMed][CrossRef]
233. Snyder M, Drlica K. 1979. DNA gyrase on the bacterial chromosome: DNA cleavage induced by oxolinic acid. J Mol Biol 131:287–302. [CrossRef]
234. Goss WA, Deitz WH, Cook TH. 1965. Mechanism of action of nalidixic acid on Escherichia coli. II. Inhibition of deoxyribonucleic acid synthesis. J Bacteriol 89:1068–1074. [PubMed]
235. Pohlhaus JR, Kreuzer KN. 2005. Norfloxacin-induced DNA gyrase cleavage complexes block Escherichia coli replication forks, causing double-stranded breaks in vivo. Mol Microbiol 56:1416–1429. [PubMed][CrossRef]
236. Zhao X, Quinn B, Kerns R, Drlica K. 2006. Bactericidal activity and target preference of a piperazinyl-cross-linked ciprofloxacin dimer with Staphylococcus aureus and Escherichia coli. J Antimicrob Chemother 58:1283–1286. [PubMed][CrossRef]
237. McPartland A, Green L, Echols H. 1980. Control of recA gene RNA in E. coli: regulatory and signal genes. Cell 20:731–737. [PubMed][CrossRef]
238. Diver JM, Wise R. 1986. Morphological and biochemical changes in Escherichia coli after exposure to ciprofloxacin. J Antimicrob Chemother 18(Suppl. D):31–41. [PubMed]
239. Chen C-R, Malik M, Snyder M, Drlica M. 1996. DNA gyrase and topoisomerase IV on the bacterial chromosome: quinolone-induced DNA cleavage. J Mol Biol 258:627–637. [PubMed][CrossRef]
240. Malik M, Zhao X, Drlica K. 2006. Lethal fragmentation of bacterial chromosomes mediated by DNA gyrase and quinolones. Mol Microbiol 61:810–825. [PubMed][CrossRef]
241. Newmark KG, O’Reilly EK, Pohlhaus JR, Kreuzer KN. 2005. Genetic analysis of the requirements for SOS induction by nalidixic acid in Escherichia coli. Gene 356:69–76. [PubMed][CrossRef]
242. Domagala JM, Hanna LD, Heifetz CL, Hutt MP, Mich TF, Sanchez JP, Solomon M. 1986. New structure-activity relationships of the quinolone antibacterials using the target enzyme. The development and application of a DNA gyrase assay. J Med Chem 29:394–404. [PubMed][CrossRef]
243. Maruri F, Sterling TR, Kaiga AW, Blackman A, van der Heijden YF, Mayer C, Cambau E, Aubry A. 2012. A systematic review of gyrase mutations associated with fluoroquinolone-resistant Mycobacterium tuberculosis and a proposed gyrase numbering system. J Antimicrob Chemother 67:819–831. [PubMed][CrossRef]
244. Drlica K, Hiasa H, Kerns R, Malik M, Mustaev A, Zhao X. 2009. Quinolones: action and resistance updated. Curr Top Med Chem 9:981–998. [PubMed][CrossRef]
245. Khodursky AB, Zechiedrich EL, Cozzarelli NR. 1995. Topoisomerase IV is a target of quinolones in Escherichia coli. Proc Natl Acad Sci USA 92:11801–11805. [PubMed][CrossRef]
246. Ng EY, Trucksis M, Hooper DC. 1996. Quinolone resistance in topoisomerase IV: relationship to the flqA locus and genetic evidence that topoisomerase IV is the primary target and DNA gyrase is the secondary target of fluoroquinolones in Staphylococcus aureus. Antimicrob Agents Chemother 40:1881–1888. [PubMed]
247. Yamagishi J-I, Kojima T, Oyamada Y, Fujimoto K, Hattori H, Nakamura S, Inoue M. 1996. Alterations in the DNA topoisomerase IV grlA gene responsible for quinolone resistance in Staphylococcus aureus. Antimicrob Agents Chemother 40:1157–1163. [PubMed]
248. Yoshida H, Bogaki M, Nakamura M, Nakamura S. 1990. Quinolone resistance-determining region in the DNA gyrase gyrA gene of Escherichia coli. Antimicrob Agents Chemother 34:1271–1272. [PubMed][CrossRef]
249. Vila I, Ruiz J, Goni P, Jimenez de Anta MT. 1996. Detection of mutations in parC in quinolone-resistant clinical isolates of Escherichia coli. Antimicrob Agents Chemother 40:491–493. [PubMed]
250. Gensberg K, Jin YF, Piddock LJV. 1995. A novel gyrB mutation in a fluoroquinolone-resistant clinical isolate of Salmonella typhimurium. FEMS Microbiol Lett 132:57–60. [PubMed][CrossRef]
251. Heisig P. 1993. High-level fluoroquinolone resistance in a Salmonella typhimurium isolate due to alterations in both gyr A and gyr B genes. J Antimicrob Chemother 32:367–377. [PubMed][CrossRef]
252. Yamagishi J, Yoshida H, Yamyoshi M, Nakamura S. 1986. Nalidixic acid-resistant mutations of the gyrB gene of Escherichia coli.Mol Gen Genet 204:367–373. [PubMed][CrossRef]
253. Heisig P, Kratz B, Halle E, Graser Y, Altwegg M, Rabsch W, Faber JP. 1995. Identification of DNA gyrase A mutations in ciprofloxacin-resistant isolates of Salmonella typhimurium from men and cattle in Germany. Microb Drug Resist 1:211–218. [PubMed][CrossRef]
254. Reyna F, Huesca M, Gonzalez V, Fuchs LY. 1995. Salmonella typhimurium gyrA mutations associated with fluoroquinolone resistance. Antimicrob Agents Chemother 39:1621–1623. [PubMed][CrossRef]
255. Willmott CJR, Maxwell A. 1993. A single point mutation in the DNA gyrase A protein greatly reduces the binding of fluoroquinolones to the gyrase-DNA complex. Antimicrob Agents Chemother 37:126–127. [PubMed][CrossRef]
256. Friedman SM, Lu T, Drlica K. 2001. Mutation in the DNA gyrase A gene of Escherichia coli that expands the quinolone resistance-determining region. Antimicrob Agents Chemother 45:2378–2380. [PubMed][CrossRef]
257. Yamagishi J, Furutani Y, Inoue S, Ohue T, Nakamura S, Shimizu M. 1981. New nalidixic acid resistance mutations related to deoxyribonucleic acid gyrase activity. J Bacteriol 148:450–458. [PubMed]
258. Heddle J, Maxwell A. 2002. Quinolone-binding pocket of DNA gyrase: role of GyrB. Antimicrob Agents Chemother 46:1805–1815. [PubMed][CrossRef]
259. Jacoby GA, Chow N, Waites KB. 2003. Prevalence of plasmid-mediated quinolone resistance. Antimicrob Agents Chemother 47:559–562. [PubMed][CrossRef]
260. Vetting MW, Hegde SS, Fajardo JE, Fiser A, Roderick SL, Takiff HE, Blanchard JS. 2006. Pentapeptide repeat proteins. Biochemistry 45:1–10. [PubMed][CrossRef]
261. Herrero M, Kolter R, Moreno F. 1986. Effects of microcin B17 on microcin B17-immune cells. J Gen Microbiol 132:403–410. [PubMed][CrossRef]
262. Vizán J, Hernandex-Chico C, del Castillo I, Moreno F. 1991. The peptide antibiotic microcin B17 induces double-strand cleavage of DNA mediated by E. coli DNA gyrase. EMBO J 10:467–476. [PubMed]
263. Heddle JG, Blance SJ, Zamble DB, Hollfelder F, Miller DA, Wentzell LM, Walsh CT, Maxwell A. 2001. The antibiotic microcin B17 is a DNA gyrase poison: characterisation of the mode of inhibition. J Mol Biol 307:1223–1234. [PubMed][CrossRef]
264. Pierrat OA, Maxwell A. 2003. The action of the bacterial toxin microcin B17: insight into the cleavage-religation reaction of DNA gyrase. J Biol Chem 278:35016–35023. [PubMed][CrossRef]
265. Pierrat OA, Maxwell A. 2005. Evidence for the role of DNA strand passage in the mechanism of action of microcin B17 on DNA gyrase. Biochemistry 44:4204–4215. [PubMed][CrossRef]
266. del Castillo FJ, del Castillo I, Moreno F. 2001. Construction and characterization of mutations at codon 751 of the Escherichia coli gyrB gene that confer resistance to the antimicrobial peptide microcin B17 and alter the activity of DNA gyrase. J Bacteriol 183:2137–2140. [PubMed][CrossRef]
267. Parks WM, Bottrill AR, Pierrat OA, Durrant MC, Maxwell A. 2007. The action of the bacterial toxin, microcin B17, on DNA gyrase. Biochimie 89:500–507. [PubMed][CrossRef]
268. Thompson RE, Jolliffe KA, Payne RJ. 2011. Total synthesis of microcin B17 via a fragment condensation approach. Org Lett 13:680–683. [PubMed][CrossRef]
269. Videnov G, Kaiser D, Brooks M, Jung G. 1996. Synthesis of the DNA gyrase inhibitor microcin B17, a 43-peptie antibiotic with eight heterocycles in its backbone. Angew Chem Int Ed Engl 35:1506–1508. [CrossRef]
270. Collin F, Thompson RE, Jolliffe KA, Payne RJ, Maxwell A. 2013. Fragments of the bacterial toxin microcin b17 as gyrase poisons. PLoS One 8:e61459. [PubMed][CrossRef]
271. Garrido MC, Herrero M, Kolter R, Moreno F. 1988. The export of the DNA replication inhibitor microcin B17 provides immunity for the host cell. EMBO J 7:1853–1862. [PubMed]
272. San Millan JL, Hernandez-Chico C, Pereda P, Moreno F. 1985. Cloning and mapping of the genetic determinants for microcin B17 production and immunity. J Bacteriol 163:275–281. [PubMed]
273. Birch RG, Patil SS. 1985. Preliminary characterization of an antibiotic produced by Xanthomonas albilineans which inhibits DNA synthesis in Escherichia coli. J Gen Microbiol 131:1069–1075. [PubMed][CrossRef]
274. Hashimi SM, Wall MK, Smith AB, Maxwell A, Birch RG. 2007. The phytotoxin albicidin is a novel inhibitor of DNA gyrase. Antimicrob Agents Chemother 51:181–187. [PubMed][CrossRef]
275. Hashimi SM, Huang G, Maxwell A, Birch RG. 2008. DNA gyrase from the albicidin producer Xanthomonas albilineans has multiple-antibiotic resistance and unusual enzymatic properties. Antimicrob Agents Chemother 52:1382–1390. [PubMed][CrossRef]
276. Rott PC, Costet L, Davis MJ, Frutos R, Gabriel DW. 1996. At least two separate gene clusters are involved in albicidin production by Xanthomonas albilineans. J Bacteriol 178:4590–4596. [PubMed]
277. Vivien E, Pitorre D, Cociancich S, Pieretti I, Gabriel DW, Rott PC, Royer M. 2007. Heterologous production of albicidin: a promising approach to overproducing and characterizing this potent inhibitor of DNA gyrase. Antimicrob Agents Chemother 51:1549–1552. [PubMed][CrossRef]
278. Miki T, Chang Z-T, Horiuchi T. 1984. Control of cell division by sex factor F in Escherichia coli. II. Identification of genes for inhibitor protein and trigger protein on the 42.84-43.6 F segment. J Mol Biol 174:627–646. [PubMed][CrossRef]
279. Miki T, Park JA, Nagao K, Murayama N, Horiuchi T. 1992. Control of segregation of chromosomal DNA by sex factor F in Escherichia coli. J Mol Biol 225:39–52. [PubMed][CrossRef]
280. Miki T, Yoshioka K, Horiuchi T. 1984. Control of cell division by sex factor F in Escherichia coli. I. The 42.84-43.6 F segment couples cell division of the host bacteria with replication of plasmid DNA. J Mol Biol 174:605–625. [PubMed][CrossRef]
281. Hayes F. 2003. Toxins-antitoxins: plasmid maintenance, programmed cell death, and cell cycle arrest. Science 301:1496–1499. [PubMed][CrossRef]
282. Bernard P, Couturier M. 1992. Cell killing by the F plasmid CcdB protein involves poisoning of the DNA-topoisomerase II complex. J Mol Biol 226:735–745. [PubMed][CrossRef]
283. Van Melderen L, Bernard P, Couturier M. 1994. Lon-dependent proteolysis of CcdA is the key control for activation of CcdB in plasmid-free segregant bacteria. Mol Microbiol 11:1151–1157. [PubMed][CrossRef]
284. Dao-Thi MH, Van Melderen L, De Genst E, Afif H, Buts L, Wyns L, Loris R. 2005. Molecular basis of gyrase poisoning by the addiction toxin CcdB. J Mol Biol 348:1091–1102. [PubMed][CrossRef]
285. Smith AB, Maxwell A. 2006. A strand-passage conformation of DNA gyrase is required to allow the bacterial toxin, CcdB, to access its binding site. Nucleic Acids Res 34:4667–4676. [PubMed][CrossRef]
286. Bernard P, Kézdy KE, Van Melderen L, Steyaert J, Wyns L, Pato ML, Higgins NP, Couturier M. 1993. The F plasmid CcdB protein induces efficient ATP-dependent DNA cleavage by gyrase. J Mol Biol 234:534–541. [PubMed][CrossRef]
287. Critchlow SE, O’Dea MH, Howells AJ, Couturier M, Gellert M, Maxwell A. 1997. The interaction of the F-plasmid killer protein, CcdB, with DNA gyrase: induction of DNA cleavage and blocking of transcription. J Mol Biol 273:826–839. [PubMed][CrossRef]
288. De Jonge N, Garcia-Pino A, Buts L, Haesaerts S, Charlier D, Zangger K, Wyns L, De Greve H, Loris R. 2009. Rejuvenation of CcdB-poisoned gyrase by an intrinsically disordered protein domain. Mol Cell 35:154–163. [PubMed][CrossRef]
289. Trovatti E, Cotrim CA, Garrido SS, Barros RS, Marchetto R. 2008. Peptides based on CcdB protein as novel inhibitors of bacterial topoisomerases. Bioorg Med Chem Lett 18:6161–6164. [PubMed][CrossRef]
290. Tran JH, Jacoby GA, Hooper DC. 2005. Interaction of the plasmid-encoded quinolone resistance protein QnrA with Escherichia coli topoisomerase IV. Antimicrob Agents Chemother 49:3050–3052. [PubMed][CrossRef]
291. Tran JH, Jacoby GA, Hooper DC. 2005. Interaction of the plasmid-encoded quinolone resistance protein Qnr with Escherichia coli DNA gyrase. Antimicrob Agents Chemother 49:118–125. [PubMed][CrossRef]
292. Bateman A, Murzin AG, Teichmann SA. 1998. Structure and distribution of pentapeptide repeats in bacteria. Protein Sci 7:1477–1480. [PubMed][CrossRef]
293. Hegde SS, Vetting MW, Roderick SL, Mitchenall LA, Maxwell A, Takiff HE, Blanchard JS. 2005. A fluoroquinolone resistance protein from Mycobacterium tuberculosis that mimics DNA. Science 308:1480–1483. [PubMed][CrossRef]
294. Hegde SS, Vetting MW, Mitchenall LA, Maxwell A, Blanchard JS. 2011. Structural and biochemical analysis of the pentapeptide repeat protein EfsQnr, a potent DNA gyrase inhibitor. Antimicrob Agents Chemother 55:110–117. [PubMed][CrossRef]
295. Xiong X, Bromley EH, Oelschlaeger P, Woolfson DN, Spencer J. 2011. 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 39:3917–3927. [PubMed][CrossRef]
296. Maxwell A. 1997. DNA gyrase as a drug target. Trends Microbiol 5:102–109. [PubMed][CrossRef]
297. Maxwell A, Lawson DM. 2003. The ATP-binding site of type II topoisomerases as a target for antibacterial drugs. Curr Top Med Chem 3:283–303. [PubMed][CrossRef]
298. Pauptit R, Weston S, Breeze A, Derbyshire D, Tucker A, Hales N, Hollinshead D, Timms D. 1998. Antibacterial design based on the structures of gyrase-inhibitor complexes, p 255–270. In Codding PW (ed), Structure-Based Drug Design. Kluwer Academic Publishers, Dordrecht, Germany. [CrossRef]
299. Angehrn P, Buchmann S, Funk C, Goetschi E, Gmuender H, Hebeisen P, Kostrewa D, Link H, Luebbers T, Masciadri R, Nielsen J, Reindl P, Ricklin F, Schmitt-Hoffmann A, Theil FP. 2004. New antibacterial agents derived from the DNA gyrase inhibitor cyclothialidine. J Med Chem 47:1487–1513. [PubMed][CrossRef]
300. Kawada S, Yamashita Y, Fujii N, Nakano H. 1991. Induction of a heat-stable topoisomerase II-DNA cleavable complex by nonintercalative terpenoides, terpentecin and clerocidin. Cancer Res 51:2922–2925. [PubMed]
301. McCullough JE, Muller MT, Howells AJ, Maxwell A, J. OS, Summerill RS, Parker WL, Wells JS, Bonner DP, Fernandes PB. 1993. Clerocidin, a terpenoid antibiotic, inhibits bacterial DNA gyrase. J Antibiot 46:526–530. [PubMed][CrossRef]
302. Richter SN, Leo E, Giaretta G, Gatto B, Fisher LM, Palumbo M. 2006. Clerocidin interacts with the cleavage complex of Streptococcus pneumoniae topoisomerase IV to induce selective irreversible DNA damage. Nucleic Acids Res 34:1982–1991. [PubMed][CrossRef]
303. Pan XS, Dias M, Palumbo M, Fisher LM. 2008. Clerocidin selectively modifies the gyrase-DNA gate to induce irreversible and reversible DNA damage. Nucleic Acids Res 36:5516–5529. [PubMed][CrossRef]
304. Nakanishi A, Imajoh-Ohmi S, Hanaoka F. 2002. Characterization of the interaction between DNA gyrase inhibitor and DNA gyrase of Escherichia coli. J Biol Chem 277:8949–8954. [PubMed][CrossRef]
305. Nakanishi A, Oshida T, Matsushita T, Imajoh-Ohmi S, Ohnuki T. 1998. Identification of DNA gyrase inhibitor (GyrI) in Escherichia coli. J Biol Chem 273:1933–1938. [PubMed][CrossRef]
306. Baquero MR, Bouzon M, Varea J, Moreno F. 1995. sbmC, a stationary-phase induced SOS Escherichia coli gene, whose product protects cells from the DNA replication inhibitor microcin B17. Mol Microbiol 18:301–311. [PubMed][CrossRef]
307. Chatterji M, Nagaraja V. 2002. GyrI: a counter-defensive strategy against proteinaceous inhibitors of DNA gyrase. EMBO Rep 3:261–267. [PubMed][CrossRef]
308. Chatterji M, Sengupta S, Nagaraja V. 2003. Chromosomally encoded gyrase inhibitor GyrI protects Escherichia coli against DNA-damaging agents. Arch Microbiol 180:339–346. [PubMed][CrossRef]
309. Karkare S, Chung TT, Collin F, Mitchenall LA, McKay AR, Greive SJ, Meyer JJ, Lall N, Maxwell A. 2013. The naphthoquinone diospyrin is an inhibitor of DNA gyrase with a novel mechanism of action. J Biol Chem 288:5149–5156. [PubMed][CrossRef]
310. Manchester JI, Dussault DD, Rose JA, Boriack-Sjodin PA, Uria-Nickelsen M, Ioannidis G, Bist S, Fleming P, Hull KG. 2012. Discovery of a novel azaindole class of antibacterial agents targeting the ATPase domains of DNA gyrase and topoisomerase IV. Bioorg Med Chem Lett 22:5150–5156. [PubMed][CrossRef]
311. Eakin AE, Green O, Hales N, Walkup GK, Bist S, Singh A, Mullen G, Bryant J, Embrey K, Gao N, Breeze A, Timms D, Andrews B, Uria-Nickelsen M, Demeritt J, Loch JT III, Hull K, Blodgett A, Illingworth RN, Prince B, Boriack-Sjodin PA, Hauck S, MacPherson LJ, Ni H, Sherer B. 2012. Pyrrolamide DNA gyrase inhibitors: fragment-based nuclear magnetic resonance screening to identify antibacterial agents. Antimicrob Agents Chemother 56:1240–1246. [PubMed][CrossRef]
312. Dale AG, Hinds J, Mann J, Taylor PW, Neidle S. 2012. Symmetric bis-benzimidazoles are potent anti-staphylococcal agents with dual inhibitory mechanisms against DNA gyrase. Biochemistry 51:5860–5871. [PubMed][CrossRef]
313. Maxwell A, Gellert M. 1986. Mechanistic aspects of DNA topoisomerases. Adv Protein Chem 38:69–107. [PubMed][CrossRef]
314. Viard T, de la Tour CB. 2007. Type IA topoisomerases: a simple puzzle? Biochimie 89:456–467. [PubMed][CrossRef]
315. Ball P. 2000. Quinolone generations: natural history or natural selection? J Antimicrob Chemother 46(Suppl T1):17–24. [PubMed]
316. Oliphant CM, Green GM. 2002. Quinolones: a comprehensive review. Am Fam Physician 65:455–464. [PubMed]
317. journal-id:
ecosalplus.ESP-0010-2014.citations
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/content/journal/ecosalplus/10.1128/ecosalplus.ESP-0010-2014
2015-04-17
2017-04-29

Abstract:

DNA topoisomerases are enzymes that control the topology of DNA in all cells. There are two types, I and II, classified according to whether they make transient single- or double-stranded breaks in DNA. Their reactions generally involve the passage of a single- or double-strand segment of DNA through this transient break, stabilized by DNA-protein covalent bonds. All topoisomerases can relax DNA, but DNA gyrase, present in all bacteria, can also introduce supercoils into DNA. Because of their essentiality in all cells and the fact that their reactions proceed via DNA breaks, topoisomerases have become important drug targets; the bacterial enzymes are key targets for antibacterial agents. This article discusses the structure and mechanism of topoisomerases and their roles in the bacterial cell. Targeting of the bacterial topoisomerases by inhibitors, including antibiotics in clinical use, is also discussed.

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Figures

Image of Figure 1
Figure 1

Examples of specific type I topoisomerases that catalyze the indicated reactions are given above the arrows. It is important to note that in the decatenation/catenation reaction, the non-nicked plasmid may be supercoiled before decatenation/catenation occurs; for illustrative purposes it has been drawn as relaxed. (Adapted from reference 313 with permission of the publisher.) doi:10.1128/ecosalplus.ESP-0010-2014.f1

Citation: Bush N, Evans-Roberts K, Maxwell A. 2015. DNA Topoisomerases, EcoSal Plus 2015; doi:10.1128/ecosalplus.ESP-0010-2014
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Image of Figure 2
Figure 2

Examples of specific type II topoisomerases that catalyze the indicated reactions are given above the arrows. It is important to note that in the decatenation/catenation reaction, the plasmids may be supercoiled before decatenation/catenation occurs; for illustrative purposes they have been drawn as relaxed. Although only relaxation of negative supercoils is shown, all known type II topoisomerases can relax positively supercoiled DNA as well. (Redrawn from reference 313 with permission of the publisher.) doi:10.1128/ecosalplus.ESP-0010-2014.f2

Citation: Bush N, Evans-Roberts K, Maxwell A. 2015. DNA Topoisomerases, EcoSal Plus 2015; doi:10.1128/ecosalplus.ESP-0010-2014
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Image of Figure 3
Figure 3

The chromosome is separated into domains with the boundaries represented as orange boxes; the replication fork is in the center. Positive supercoiling occurs ahead of the replication fork, and precatenanes may form behind it. (Reprinted from reference 9 . Copyright 2001 National Academy of Sciences, U.S.A.) doi:10.1128/ecosalplus.ESP-0010-2014.f3

Citation: Bush N, Evans-Roberts K, Maxwell A. 2015. DNA Topoisomerases, EcoSal Plus 2015; doi:10.1128/ecosalplus.ESP-0010-2014
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Image of Figure 4
Figure 4

( and ) Converging replication forks (a) lead to the interwinding of daughter molecules and the formation of precatenanes (b). () Upon the completion of replication, the products are catenated DNA circles. (Reprinted from reference 2 with permission of the publisher.) doi:10.1128/ecosalplus.ESP-0010-2014.f4

Citation: Bush N, Evans-Roberts K, Maxwell A. 2015. DNA Topoisomerases, EcoSal Plus 2015; doi:10.1128/ecosalplus.ESP-0010-2014
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Image of Figure 5
Figure 5

Black bars indicate catalytic residues. Y is the catalytic tyrosine which forms the covalent bond with the phosphodiester backbone of the cleaved single-strand of DNA (319 in topo I, 328 in topo III, 809 in reverse gyrase, 723 in human topo I, and 226 in topo V) (for a full description of all catalytic residues, see reference 147 ). In type IB, NTD is the N-terminal domain, CTD is the C-terminal domain. In type IC, HTH is helix-turn-helix, HhH is helix-hairpin-helix. (Adapted from reference 148 . Schoeffler AJ, Berger JM. 2008. DNA topoisomerases: harnessing and constraining energy to govern chromosome topology. 41–101. © Cambridge University Press, reproduced with permission.) doi:10.1128/ecosalplus.ESP-0010-2014.f5

Citation: Bush N, Evans-Roberts K, Maxwell A. 2015. DNA Topoisomerases, EcoSal Plus 2015; doi:10.1128/ecosalplus.ESP-0010-2014
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Image of Figure 6
Figure 6

Black bars indicate catalytic residues. Y is the catalytic tyrosine which forms the covalent bond with the phosphodiester backbone of the cleaved strand of DNA (782 in topo II, 122 in DNA gyrase, 120 in topo IV, and 105 in topo VI) (for full description of all catalytic residues, see reference 148 ). GHKL is the ATPase domain, TOPRIM stands for topoisomerase/primase domain, WHD is the winged-helix domain, CTD is the C-terminal domain, H2tH is the helix-helix-turn helix domain, and Ig is an immunoglobulin-type fold (not seen in all species). (Adapted from reference 148 . Schoeffler AJ, Berger JM. 2008. DNA topoisomerases: harnessing and constraining energy to govern chromosome topology. 41–101. © Cambridge University Press, reproduced with permission.) doi:10.1128/ecosalplus.ESP-0010-2014.f6

Citation: Bush N, Evans-Roberts K, Maxwell A. 2015. DNA Topoisomerases, EcoSal Plus 2015; doi:10.1128/ecosalplus.ESP-0010-2014
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Image of Figure 7
Figure 7

A ribbon representation of the overall structure of the protein is presented, with four subdomains (DI to DIV) shown in different colors. The bound DNA is shown in green as an electron density map. (Reprinted from reference 23 with permission of the publisher.) doi:10.1128/ecosalplus.ESP-0010-2014.f7

Citation: Bush N, Evans-Roberts K, Maxwell A. 2015. DNA Topoisomerases, EcoSal Plus 2015; doi:10.1128/ecosalplus.ESP-0010-2014
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Image of Figure 8
Figure 8

The enzyme binds DNA (T segment in red, G segment in black; not to scale) and cleaves one strand (active-site tyrosine in purple), forming a 5′-phosphodiester linkage. The complementary strand is passed through the gap and into the central cavity of the enzyme. The light blue circles indicate areas of structural changes during the open conformation of the enzyme. The nick is resealed, and the strand is released. It is possible that the cycle proceeds in reverse with the T segment being passed out of the enzyme rather than in (steps 7 through 1 rather than 1 through 7) ( 24 ). (This figure was published in Viard T, de la Tour CB. 2007. Type IA topoisomerases: a simple puzzle? Biochimie 456–467. Copyright © 2007 Elsevier Masson SAS. [ 314 ] All rights reserved.) doi:10.1128/ecosalplus.ESP-0010-2014.f8

Citation: Bush N, Evans-Roberts K, Maxwell A. 2015. DNA Topoisomerases, EcoSal Plus 2015; doi:10.1128/ecosalplus.ESP-0010-2014
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Image of Figure 9
Figure 9

One monomer is shaded grey, and the other is colored by functional region. WHD is the winged-helix domain, TOPRIM is the topoisomerase-primase domain. The black box indicates the position of ADPNP, and green indicates DNA. (Reprinted from reference 77 with permission of the publisher.) doi:10.1128/ecosalplus.ESP-0010-2014.f9

Citation: Bush N, Evans-Roberts K, Maxwell A. 2015. DNA Topoisomerases, EcoSal Plus 2015; doi:10.1128/ecosalplus.ESP-0010-2014
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Image of Figure 10
Figure 10

() Structure of the ParE-ParC55 fusion construct ( 122 ) (PDB: 4I3H). Yellow indicates the GHKL domain, orange is the transducer domain, teal is the winged-helix domain (WHD), purple is the tower domain, and blue shows the coiled-coil domain (see Fig. 6 for domain structure). () Space-filled model of the structure shown in panel A. () ParE 43-kDa N-terminal fragment complexed with ADPNP (black box) (PDB: 1S16) ( 114 ). It is proposed that the open conformation of ParE as seen in panel A is the conformation pre-ATP binding whereas the conformation seen in panel C is the post-ATP-binding conformation. () ParC C-terminal domain in two orientations (PDB: 1ZVT) ( 115 ). doi:10.1128/ecosalplus.ESP-0010-2014.f10

Citation: Bush N, Evans-Roberts K, Maxwell A. 2015. DNA Topoisomerases, EcoSal Plus 2015; doi:10.1128/ecosalplus.ESP-0010-2014
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Image of Figure 11
Figure 11

() Model of the full-length structure of DNA gyrase. Yellow indicates the GHKL domain, orange is the transducer domain, teal is the winged-helix domain (WHD), purple is the tower domain, blue shows the coiled-coil domain, and pink indicates the C-terminal domain (see Fig. 6 for the domain structure). The full-length protein structure was modeled on the GyrB 43-kDa fragment (PDB: 1EI1), a B-A fusion construct (PDB: 3NUH) ( 144 ), and the GyrA 35-kDa C-terminal domain (PDB: 3L6V). () Space-filled model of the structure shown in panel A. (C) Four principal domains of gyrase. 1 is the GyrB 43-kDa fragment complexed with ADPNP; 2 is the GyrB TOPRIM domain; 3 is the GyrA 59-kDa subunit; 4 is the GyrA C-terminal domain in two orientations (PDB: 1ZI0). doi:10.1128/ecosalplus.ESP-0010-2014.f11

Citation: Bush N, Evans-Roberts K, Maxwell A. 2015. DNA Topoisomerases, EcoSal Plus 2015; doi:10.1128/ecosalplus.ESP-0010-2014
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Figure 12

In particular, the crystal structures of the ATPase (PDB:1EI1) and the DNA-binding-cleavage domain in the presence of ciprofloxacin (PDB:2XCT) were modeled into the core of the map with the two additional densities on both side of the core enzyme accommodating the C-terminal domains (PDB:3L6V). (Reprinted from reference 162 with permission of the publisher.) doi:10.1128/ecosalplus.ESP-0010-2014.f12

Citation: Bush N, Evans-Roberts K, Maxwell A. 2015. DNA Topoisomerases, EcoSal Plus 2015; doi:10.1128/ecosalplus.ESP-0010-2014
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Image of Figure 13
Figure 13

The domains are colored as follows: GyrB43, dark blue; GyrB TOPRIM, red; GyrB tail, green; GyrA59, orange; GyrA C-terminal domain, light blue. The G and T DNA segments are colored black and purple, respectively. 1, subunits and DNA in their proposed free states in solution. Stars indicate the active-site residues for DNA cleavage, and the circle indicates the ATP-binding pocket. 2, The G segment binds across GyrA at the dimer interface, and the GyrA C-terminal domain wraps the DNA to present the T segment in a positive crossover. 3, ATP is bound, which closes the GyrB clamp capturing the T segment, and the G segment is transiently cleaved. 4, Hydrolysis of one ATP molecule allows GyrB to rotate, the DNA gate to widen, and the T segment to be transported through the cleaved G segment. 5, The T segment exits through the C gate, and the G segment is religated. The hydrolysis of the remaining ATP molecule resets the enzyme. The right panel shows the side view for illustrations 2 through 4. (Reprinted from reference 145 with permission of the publisher.) doi:10.1128/ecosalplus.ESP-0010-2014.f13

Citation: Bush N, Evans-Roberts K, Maxwell A. 2015. DNA Topoisomerases, EcoSal Plus 2015; doi:10.1128/ecosalplus.ESP-0010-2014
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Figure 14

Structures of aminocoumarins. doi:10.1128/ecosalplus.ESP-0010-2014.f14

Citation: Bush N, Evans-Roberts K, Maxwell A. 2015. DNA Topoisomerases, EcoSal Plus 2015; doi:10.1128/ecosalplus.ESP-0010-2014
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Figure 15

Part of the N-terminal GyrB structure is shown, with ADPNP in red and novobiocin in blue ( 204 ). doi:10.1128/ecosalplus.ESP-0010-2014.f15

Citation: Bush N, Evans-Roberts K, Maxwell A. 2015. DNA Topoisomerases, EcoSal Plus 2015; doi:10.1128/ecosalplus.ESP-0010-2014
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Figure 16

Structure of simocyclinone D8. doi:10.1128/ecosalplus.ESP-0010-2014.f16

Citation: Bush N, Evans-Roberts K, Maxwell A. 2015. DNA Topoisomerases, EcoSal Plus 2015; doi:10.1128/ecosalplus.ESP-0010-2014
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Figure 17a

The protein dimer is shown in gold and blue (ribbon representation), and the bound simocyclinone D8 dimer is shown in space-filling representation. () Side view. () Top view. Note that the polyketide end of each simocyclinone molecule also binds to the other monomer across the dimer (DNA-gate) interface ( 221 ). doi:10.1128/ecosalplus.ESP-0010-2014.f17a

Citation: Bush N, Evans-Roberts K, Maxwell A. 2015. DNA Topoisomerases, EcoSal Plus 2015; doi:10.1128/ecosalplus.ESP-0010-2014
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Figure 17b

The protein dimer is shown in gold and blue (ribbon representation), and the bound simocyclinone D8 dimer is shown in space-filling representation. () Side view. () Top view. Note that the polyketide end of each simocyclinone molecule also binds to the other monomer across the dimer (DNA-gate) interface ( 221 ). doi:10.1128/ecosalplus.ESP-0010-2014.f17b

Citation: Bush N, Evans-Roberts K, Maxwell A. 2015. DNA Topoisomerases, EcoSal Plus 2015; doi:10.1128/ecosalplus.ESP-0010-2014
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Figure 18

Quinolones are divided into generations based on their antibacterial spectrum. The first-generation drugs (e.g., nalidixic acid and oxolinic acid) are examples of older acidic (narrow-spectrum) quinolones, whereas the higher-generation drugs (e.g., ciprofloxacin, sparfloxacin, and gatifloxacin) are examples of the amphoteric fluoroquinolones (expanded-spectrum compounds) ( 315 , 316 ). doi:10.1128/ecosalplus.ESP-0010-2014.f18

Citation: Bush N, Evans-Roberts K, Maxwell A. 2015. DNA Topoisomerases, EcoSal Plus 2015; doi:10.1128/ecosalplus.ESP-0010-2014
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Figure 19

() ParE28-ParC58 is a fusion of the C-terminal region of ParE and the N-terminal region of ParC. () ParE28-ParC58 complex with DNA (green), moxifloxacin (yellow carbons), and Mg ions (orange spheres). One fused ParE-ParC subunit is shown in red-blue; the other is all gray. (Reprinted from reference 163 with permission of the publisher.) doi:10.1128/ecosalplus.ESP-0010-2014.f19

Citation: Bush N, Evans-Roberts K, Maxwell A. 2015. DNA Topoisomerases, EcoSal Plus 2015; doi:10.1128/ecosalplus.ESP-0010-2014
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Figure 20

Structure of the DNA gyrase inhibitor MccB17. doi:10.1128/ecosalplus.ESP-0010-2014.f20

Citation: Bush N, Evans-Roberts K, Maxwell A. 2015. DNA Topoisomerases, EcoSal Plus 2015; doi:10.1128/ecosalplus.ESP-0010-2014
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Figure 21

() Crystal structure of GyrA59 with and without CcdB. The left panel shows the apo-structure. The green spheres indicate the positions of residues that, if mutated, confer resistance to CcdB (for an overview of these mutations, see reference 285 ). The right panel shows GyrA59 bound to CcdB (GyrA59 dimer colored blue and orange by subunit; CcdB dimer colored green and purple). () Diagram of the proposed mode of action of CcdB. The GyrB subunits are shown in yellow, the GyrA subunits are shown in green, and CcdB is shown in pink. The T segment is shown in red, and the G segment is shown in black; * represents ATP. After DNA binding and opening of the DNA gate, CcdB binds to the GyrA, blocking the T segment from exiting the C gate, and stabilizes the cleavage complex by stalling the enzyme in the open conformation. In this state there may be a futile ATP hydrolysis event which would fail to reset the enzyme. While only one ATP molecule is shown in the model, it is possible that at this stage two molecules of ATP may be bound (for the full catalytic cycle, see Fig. 13 ). Although this figure shows ATP binding during inhibition by CcdB, it has been shown that CcdB can stabilize the cleavage complex in the absence of ATP ( 285 ). (Redrawn from reference 285 with permission from the publisher.) doi:10.1128/ecosalplus.ESP-0010-2014.f21

Citation: Bush N, Evans-Roberts K, Maxwell A. 2015. DNA Topoisomerases, EcoSal Plus 2015; doi:10.1128/ecosalplus.ESP-0010-2014
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Tables

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Table 1

Key properties of different topoisomerases

Citation: Bush N, Evans-Roberts K, Maxwell A. 2015. DNA Topoisomerases, EcoSal Plus 2015; doi:10.1128/ecosalplus.ESP-0010-2014
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Table 2

Inhibitors of DNA gyrase

Citation: Bush N, Evans-Roberts K, Maxwell A. 2015. DNA Topoisomerases, EcoSal Plus 2015; doi:10.1128/ecosalplus.ESP-0010-2014

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