1887
No metrics data to plot.
The attempt to load metrics for this article has failed.
The attempt to plot a graph for these metrics has failed.

EcoSal Plus

Domain 4:

Synthesis and Processing of Macromolecules

DNA Topoisomerases

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.
Buy article
Choose downloadable ePub or PDF files.
Buy this Chapter
Digital (?) $30.00
  • Authors: Katherine Evans-Roberts1,4, and Anthony Maxwell2
  • Editor: Susan T. Lovett3
  • VIEW AFFILIATIONS HIDE AFFILIATIONS
    Affiliations: 1: Department of Biological Chemistry, John Innes Centre, Norwich NR4 7UH, United Kingdom; 2: Department of Biological Chemistry, John Innes Centre, Norwich NR4 7UH, United Kingdom; 3: Brandeis University, Waltham, MA
  • Received 25 September 2008 Accepted 22 December 2008 Published 29 July 2009
  • Address correspondence to Anthony Maxwell tony.maxwell@bbsrc.ac.uk.
image of DNA Topoisomerases
    Preview this reference work article:
    Zoom in
    Zoomout

    DNA Topoisomerases, Page 1 of 2

    | /docserver/preview/fulltext/ecosalplus/3/2/4_4_9_module-1.gif /docserver/preview/fulltext/ecosalplus/3/2/4_4_9_module-2.gif
  • Abstract:

    DNA topoisomerases are enzymes that control the topological state of DNA in all cells; they have central roles in DNA replication and transcription. They are classified into two types, I and II, depending on whether they catalyze reactions involving the breakage of one or both strands of DNA. Structural and mechanistic distinctions have led to further classifications: IA, IB, IC, IIA, and IIB. The essence of the topoisomerase reaction is the ability of the enzymes to stabilize transient breaks in DNA, via the formation of tyrosyl-phosphate covalent intermediates. The essential nature of topoisomerases and their ability to stabilize DNA breaks has led to them being key targets for antibacterial and anticancer agents. This chapter reviews the basic features of topoisomerases focussing mainly on the prokaryotic enzymes. We highlight recent structural advances that have given new insight into topoisomerase mechanisms and into the molecular basis of the action of topoisomerase-specific drugs.

  • Citation: Evans-Roberts K, Maxwell A. 2009. DNA Topoisomerases, EcoSal Plus 2009; doi:10.1128/ecosalplus.4.4.9

Key Concept Ranking

Type IIA Topoisomerase
0.52009964
Type IIB Topoisomerase
0.4894024
Type II Topoisomerase
0.47108534
0.52009964

Article Version

An updated version has been published for this content:
DNA Topoisomerases

References

1. Watson JD, Crick FHC. 1953. Genetical implications of the structure of deoxyribonucleic acid. Nature 171:964–967.[PubMed]
2. Champoux JJ. 2001. DNA topoisomerases: structure, function, and mechanism. Annu Rev Biochem 70:369–413. [PubMed][CrossRef]
3. Corbett KD, Berger JM. 2004. Structure, molecular mechanisms, and evolutionary relationships in DNA topoisomerases. Annu Rev Biophys Biomol Struct 33:95–118. [PubMed][CrossRef]
4. Forterre P, Gribaldo S, Gadelle D, Serre MC. 2007. Origin and evolution of DNA topoisomerases. Biochimie 89:427–446. [PubMed][CrossRef]
5. Wang JC. 2002. Cellular roles of DNA topoisomerases: a molecular perspective. Nat Rev Mol Cell Biol 3:430–440. [PubMed][CrossRef]
6. Maxwell A, Gellert M. 1986. Mechanistic aspects of DNA topoisomerases. Adv Protein Chem 38:69–107. [PubMed][CrossRef]
7. Schvartzman JB, Stasiak A. 2004. A topological view of the replicon. EMBO Rep 5:256–261. [PubMed][CrossRef]
8. 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]
9. Ullsperger CJ, Vologodskii AV, Cozzarelli NR. 1995. Unlinking of DNA by topoisomerases during DNA replication, p 115–142. In Eckstein F and Lilley DMJ (ed), Nucleic Acids and Molecular Biology, vol. 9. Springer-Verlag, Berlin, Germany.
10. Wang JC. 1996. DNA topoisomerases. Annu Rev Biochem 65:635–692. [PubMed][CrossRef]
11. Bates AD, Maxwell A. 2005. DNA Topology. Oxford University Press, Oxford, United Kingdom.
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, Moris D. 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. Lilley DMJ, Chen D, Bowater RP. 1996. DNA supercoiling and transcription: topological coupling of promoters. Q Rev Biophys 29:203–225. [PubMed][CrossRef]
16. 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]
17. 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]
18. 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]
19. Wang JC. 1971. Interaction between DNA and an Escherichia coli protein ω. J Mol Biol 55:523–533. [PubMed][CrossRef]
20. 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]
21. 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]
22. 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]
23. 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. [PubMed][CrossRef]
24. Richardson S, Higgins C, Lilley D. 1984. The genetic control of DNA supercoiling in Salmonella typhimurium. EMBO J 3:1745–1752.[PubMed]
25. Stupina VA, Wang JC. 2005. Viability of Escherichia coli topA mutants lacking DNA topoisomerase I. J Biol Chem 280:355–360.[PubMed]
26. 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]
27. 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]
28. 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]
29. 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]
30. 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]
31. DiGate RJ, Marians KJ. 1992. Escherichia coli topoisomerase III-catalyzed cleavage of RNA. J Biol Chem 267:20532–20535.[PubMed]
32. 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]
33. Mondragon A, DiGate R. 1999. The structure of Escherichia coli DNA topoisomerase III. Structure 7:1373–1383. [PubMed][CrossRef]
34. 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]
35. 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]
36. 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]
37. 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]
38. Suski C, Marians KJ. 2008. Resolution of converging replication forks by RecQ and topoisomerase III. Mol Cell 30:779–789. [PubMed][CrossRef]
39. 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]
40. 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]
41. Kikuchi A, Asai K. 1984. Reverse gyrase—a topoisomerase which introduces positive superhelical turns into DNA. Nature 309:677–681. [PubMed][CrossRef]
42. 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]
43. Shibata T, Nakasu S, Yasui K, Kikuchi A. 1987. Intrinsic DNA-dependent ATPase activity of reverse gyrase. J Biol Chem 262:10419–10421.[PubMed]
44. Rodriguez AC, Stock D. 2002. Crystal structure of reverse gyrase: insights into the positive supercoiling of DNA. EMBO J 21:418–426. [PubMed][CrossRef]
45. 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]
46. 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]
47. Rodriguez AC. 2003. Investigating the role of the latch in the positive supercoiling mechanism of reverse gyrase. Biochemistry 42:5993–6004. [PubMed][CrossRef]
48. 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]
49. Hsieh T, Brutlag D. 1980. ATP-dependent DNA topoisomerase from D. melanogaster reversibly catenates duplex DNA rings. Cell 21:115–125. [PubMed][CrossRef]
50. 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]
51. 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]
52. 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]
53. 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]
54. Caron PR. 1999. Appendix: compendium of DNA topoisomerase sequences, p 279–316. In Bjornsti M-A and Osheroff N (ed), Methods in Molecular Biology, vol. 94. DNA Topoisomerase Protocols: DNA Topology and Enzymes. Humana Press, Towata, NJ.
55. 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]
56. Watt PM, Hickson ID. 1994. Structure and function of type II DNA topoisomerases. Biochem J 303:681–695.[PubMed]
57. Berger JM, Gamblin SJ, Harrison SC, Wang JC. 1996. Structure at 2.7 Å resolution of a 92K yeast DNA topoisomerase II fragment. Nature 379:225–232. [PubMed][CrossRef]
58. 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]
59. Dong KC, Berger JM. 2007. Structural basis for gate-DNA recognition and bending by type IIA topoisomerases. Nature 450:1201–1205. [PubMed][CrossRef]
60. 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]
61. Berger JM, Wang JC. 1996. Recent developments in DNA topoisomerase II structure and mechanism. Curr Opin Struct Biol 6:84–90. [PubMed][CrossRef]
62. 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]
63. 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]
64. Hartung F, Puchta H. 2000. Molecular characterisation of two paralogous SPO11 homologues in Arabidopsis thaliana. Nucleic Acids Res 28:1548–1554. [PubMed][CrossRef]
65. 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]
66. 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]
67. Corbett KD, Berger JM. 2003. Emerging roles for plant topoisomerase VI. Chem Biol 10:107–111. [PubMed][CrossRef]
68. 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]
69. 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]
70. Corbett KD, Berger JM. 2005. Structural dissection of ATP turnover in the prototypical GHL ATPase TopoVI. Structure 13:873–882. [PubMed][CrossRef]
71. 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]
72. 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]
73. 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]
74. 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]
75. Peng H, Marians KJ. 1993. Escherichia coli topoisomerase IV. J Biol Chem 268:24481–24490.[PubMed]
76. Kato J, Nishimura Y, Imamura R, Niki H, Hiraga S, Suzuki H. 1990. New topoisomerase essential for chromosome segregation in E. coli Cell 63:393–404. [PubMed][CrossRef]
77. 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]
78. Peng H, Marians KJ. 1995. The interaction of Escherichia coli topoisomerase IV with DNA. J Biol Chem 270:25286–25290. [PubMed][CrossRef]
79. 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]
80. 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]
81. Deibler RW, Rahmati S, Zechiedrich EL. 2001. Topoisomerase IV, alone, unknots DNA in E. coli. Genes Dev 15:748–761. [PubMed][CrossRef]
82. 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]
83. 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 subunits (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]
84. 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]
85. 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]
86. Morais Cabral JH, Jackson AP, Smith CV, Shikotra N, Maxwell A, Liddington RC. 1997. Structure of the DNA breakage-reunion domain of DNA gyrase. Nature 388:903–906. [PubMed][CrossRef]
87. 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]
88. 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]
89. Kampranis SC, Maxwell A. 1996. Conversion of DNA gyrase into a conventional type II topoisomerase. Proc Natl Acad Sci USA 93:14416–14421. [CrossRef]
90. 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]
91. 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]
92. 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]
93. 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]
94. 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. [CrossRef]
95. 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]
96. 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]
97. 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]
98. 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]
99. 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]
100. 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]
101. Kampranis SC, Maxwell A. 1998. Conformational changes in DNA gyrase revealed by limited proteolysis. J Biol Chem 273:22606–22614. [PubMed][CrossRef]
102. Reece RJ, Maxwell A. 1989. Tryptic fragments of the Escherichia coli DNA gyrase A protein. J Biol Chem 264:19648–19653.[PubMed]
103. 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]
104. 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]
105. 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]
106. Horowitz DS, Wang JC. 1987. Mapping the active site tyrosine of Escherichia coli DNA gyrase. J Biol Chem 262:5339–5344.[PubMed]
107. 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]
108. Tsai FT. 1996. Crystallization and preliminary crystallographic analysis of the DNA gyrase B protein from B. stearothermophilus. Acta Crystallogr D 52:1216–1218.[PubMed]
109. Dutta R, Inouye M. 2000. GHKL, an emergent ATPase/kinase superfamily. Trends Biochem Sci 25:24–28. [PubMed][CrossRef]
110. 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]
111. 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]
112. 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]
113. 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]
114. 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]
115. 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]
116. 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]
117. Liu LF, Wang JC. 1978. DNA-DNA gyrase complex: the wrapping of the DNA duplex outside the enzyme. Cell 15:979–984. [PubMed][CrossRef]
118. 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]
119. 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]
120. 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]
121. Ali JA, Jackson AP, Howells AJ, Maxwell A. 1993. The 43-kilodalton N-terminal fragment of the DNA gyrase B protein hydrolyzes ATP and binds coumarin drugs. Biochemistry 32:2717–2724. [PubMed][CrossRef]
122. 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]
123. 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]
124. 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]
125. 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]
126. 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]
127. 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]
128. 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 Pi release. J Biol Chem 276:27893–27898. [PubMed][CrossRef]
129. Bates AD, Maxwell A. 2007. Energy coupling in type II topoisomerases: why do they hydrolyze ATP? Biochemistry 46:7929–7941. [PubMed][CrossRef]
130. Williams NL, Maxwell A. 1999. Probing the two-gate mechanism of DNA gyrase using cysteine cross-linking. Biochemistry 38:13502–13511.[PubMed]
131. 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]
132. 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]
133. Kreuzer KN, Cozzarelli NR. 1980. Formation and resolution of DNA catenanes by DNA gyrase. Cell 20:245–254. [PubMed][CrossRef]
134. Gore J, Bryant Z, Stone MD, Nollmann M, Cozzarelli NR, Bustamante C. 2006. Mechanochemical analysis of DNA gyrase using rotor bead tracking. Nature 439:100–104. [PubMed][CrossRef]
135. Nollmann M, Stone MD, Bryant Z, Gore J, Crisona NJ, Hong SC, Mitelheiser S, Maxwell A, Bustamante C, Cozzarelli NR. 2007. Multiple modes of Escherichia coli DNA gyrase activity revealed by force and torque. Nat Struct Mol Biol 14:264–271. [PubMed][CrossRef]
136. Maxwell A. 1997. DNA gyrase as a drug target. Trends Microbiol 5:102–109. [PubMed][CrossRef]
137. Maxwell A. 1999. DNA gyrase as a drug target. Biochem Soc Trans 27:48–53.[PubMed]
138. Hinman JW, Hoeksema H, Caron EL, Jackson WG. 1956. The partial structure of novobiocin (streptonivicin). J Am Chem Soc 78:1072. [CrossRef]
139. Hoeksema H, Johnson JL, Hinman JW. 1955. Structural studies on Streptonivicin, a new antibiotic. J Am Chem Soc 77:6710–6711. [CrossRef]
140. 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]
141. Staudenbauer WL. 1976. Replication of Escherichia coli DNA in vitro: inhibition by oxolinic acid. Eur J Biochem 62:491–497. [PubMed][CrossRef]
142. 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]
143. 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]
144. 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]
145. 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]
146. 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]
147. 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]
148. 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]
149. Lewis RJ, Singh OMP, Smith CV, Skarynski 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]
150. Tsai FTF, Singh OMP, 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.[PubMed]
151. Hardy CD, Cozzarelli NR. 2003. Alteration of Escherichia coli topoisomerase IV to novobiocin resistance. Antimicrob Agents Chemother 47:941–947. [PubMed][CrossRef]
152. Li SM, Heide L. 2006. The biosynthetic gene clusters of aminocoumarin antibiotics. Planta Med 72:1093–1099. [PubMed][CrossRef]
153. 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]
154. 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]
155. Wang ZX, Li SM, Heide L. 2000. Identification of the coumermycin A1 biosynthetic gene cluster of Streptomyces rishiriensis DSM 40489. Antimicrob Agents Chemother 44:3040–3048.[PubMed]
156. 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]
157. 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]
158. 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]
159. 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]
160. 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]
161. 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]
162. 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]
163. 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]
164. Drlica K, Malik M. 2003. Fluoroquinolones: action and resistance. Curr Top Med Chem 3:249–282. [PubMed][CrossRef]
165. Van Bambeke F, Michot JM, Van Eldere J, Tulkens PM. 2005. Quinolones in 2005: an update. Clin Microbiol Infect 11:256–280. [PubMed][CrossRef]
166. King DE, Malone R, Lilley SH. 2000. New classification and update on the quinolone antibiotics. Am Fam Physician 61:2741–2748.[PubMed]
167. 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]
168. 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]
169. 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]
170. Drlica K, Malik M, Kerns RJ, Zhao X. 2008. Quinolone-mediated bacterial death. Antimicrob Agents Chemother 52:385–392. [PubMed][CrossRef]
171. 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]
172. Snyder M, Drlica K. 1979. DNA gyrase on the bacterial chromosome: DNA cleavage induced by oxolinic acid. J Mol Biol 131:287–302. [PubMed][CrossRef]
173. 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]
174. 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]
175. 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]
176. 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]
177. 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]
178. 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]
179. 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]
180. 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]
181. 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]
182. Hooper DC. 2003. Mechanisms of quinolone resistance, p 41–67. In Hooper DC and Rubinstein E (ed), Quinolone Antimicrobial Agents, 3rd ed. ASM Press, Washington, DC.
183. 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]
184. 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]
185. 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]
186. 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]
187. 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]
188. 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]
189. 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]
190. 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]
191. 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]
192. Reyna F, Huesca M, Gonzalez V, Fuchs LY. 1995. Salmonella typhimurium gyrA mutations associated with fluoroquinolone resistance. Antimicrob Agents Chemother 39:1621–1623.[PubMed]
193. 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]
194. 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]
195. Yoshida H, Bogaki M, Nakamura M, Yamanaka LM, Nakamura S. 1991. Quinolone resistance-determining region in the DNA gyrase gyrB gene of Escherichia coli. Antimicrob Agents Chemother 35:1647–1650.[PubMed]
196. Heddle J, Maxwell A. 2002. Quinolone-binding pocket of DNA gyrase: role of GyrB. Antimicrob Agents Chemother 46:1805–1815. [PubMed][CrossRef]
197. Jacoby GA, Chow N, Waites KB. 2003. Prevalence of plasmid-mediated quinolone resistance. Antimicrob Agents Chemother 47:559–562. [PubMed][CrossRef]
198. Vetting MW, Hegde SS, Fajardo JE, Fiser A, Roderick SL, Takiff HE, Blanchard JS. 2006. Pentapeptide repeat proteins. Biochemistry 45:1–10. [PubMed][CrossRef]
199. Heddle JG, Barnard FM, Wentzell LM, Maxwell A. 2000. The interaction of drugs with DNA gyrase: a model for the molecular basis of quinolone action. Nucleosides Nucleotides Nucleic Acids 19:1249–1264. [PubMed][CrossRef]
200. Nakamura S, Yoshida H, Bogaki M, Nakamura M, Kojima T. 1993. Quinolone resistance mutations in DNA gyrase, p 135–143. In Andoh T, Ikeda H, and Oguro M (ed), Molecular Biology of DNA Topoisomerases and Its Application to Chemotherapy. CRC Press, Inc., Boca Raton, FL.
201. 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]
202. 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]
203. 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]
204. Herrero M, Moreno F. 1986. Microcin B17 blocks DNA replication and induces the SOS system in Escherichia coli. J Gen Microbiol 132:393–402.[PubMed]
205. 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]
206. 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]
207. 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]
208. 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]
209. 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]
210. 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]
211. 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]
212. Hayes F. 2003. Toxins-antitoxins: plasmid maintenance, programmed cell death, and cell cycle arrest. Science 301:1496–1499. [PubMed][CrossRef]
213. 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]
214. 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]
215. 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]
216. 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]
217. 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]
218. 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]
219. 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. [CrossRef]
220. Bateman A, Murzin AG, Teichmann SA. 1998. Structure and distribution of pentapeptide repeats in bacteria. Protein Sci 7:1477–1480. [PubMed][CrossRef]
221. 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]
222. 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]
223. 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, The Netherlands.
224. 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]
225. 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]
226. McCullough JE, Muller MT, Howells AJ, Maxwell A, OSJ, 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]
227. 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]
228. 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]
229. 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. [CrossRef]
230. 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]
231. Chatterji M, Nagaraja V. 2002. GyrI: a counter-defensive strategy against proteinaceous inhibitors of DNA gyrase. EMBO Rep 3:261–267. [PubMed][CrossRef]
232. 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]
233. 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]
ecosalplus.4.4.9.citations
ecosalplus/3/2
content/journal/ecosalplus/10.1128/ecosalplus.4.4.9
Loading

Citations loading...

Loading

Article metrics loading...

/content/journal/ecosalplus/10.1128/ecosalplus.4.4.9
2009-07-29
2017-09-21

Abstract:

DNA topoisomerases are enzymes that control the topological state of DNA in all cells; they have central roles in DNA replication and transcription. They are classified into two types, I and II, depending on whether they catalyze reactions involving the breakage of one or both strands of DNA. Structural and mechanistic distinctions have led to further classifications: IA, IB, IC, IIA, and IIB. The essence of the topoisomerase reaction is the ability of the enzymes to stabilize transient breaks in DNA, via the formation of tyrosyl-phosphate covalent intermediates. The essential nature of topoisomerases and their ability to stabilize DNA breaks has led to them being key targets for antibacterial and anticancer agents. This chapter reviews the basic features of topoisomerases focussing mainly on the prokaryotic enzymes. We highlight recent structural advances that have given new insight into topoisomerase mechanisms and into the molecular basis of the action of topoisomerase-specific drugs.

Highlighted Text: Show | Hide
Loading full text...

Full text loading...

Comment has been disabled for this content
Submit comment
Close
Comment moderation successfully completed

Figures

Image of Figure 1
Figure 1

Reprinted from ( 6 ) with the permission of the publisher.

Citation: Evans-Roberts K, Maxwell A. 2009. DNA Topoisomerases, EcoSal Plus 2009; doi:10.1128/ecosalplus.4.4.9
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2
Figure 2

Reprinted from ( 6 ) with the permission of the publisher.

Citation: Evans-Roberts K, Maxwell A. 2009. DNA Topoisomerases, EcoSal Plus 2009; doi:10.1128/ecosalplus.4.4.9
Permissions and Reprints Request Permissions
Download as Powerpoint
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 the ( 8 ) with the permission of the publisher.

Citation: Evans-Roberts K, Maxwell A. 2009. DNA Topoisomerases, EcoSal Plus 2009; doi:10.1128/ecosalplus.4.4.9
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4
Figure 4

(a and b) Converging replication forks (a) lead to the interwinding of daughter molecules and the formation of precatenanes (b). (c) Upon the completion of replication, the products are catenated DNA circles.

Reprinted from ( 11 ) with the permission of the publisher.

Citation: Evans-Roberts K, Maxwell A. 2009. DNA Topoisomerases, EcoSal Plus 2009; doi:10.1128/ecosalplus.4.4.9
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 5
Figure 5

Reprinted from the ( 2 ) with the permission of the publisher.

Citation: Evans-Roberts K, Maxwell A. 2009. DNA Topoisomerases, EcoSal Plus 2009; doi:10.1128/ecosalplus.4.4.9
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 6
Figure 6

(a) Type IIA topoisomerases. (b) Topo VI, the only topoisomerase in the type IIB class.

Reprinted from the ( 2 ) with the permission of the publisher.

Citation: Evans-Roberts K, Maxwell A. 2009. DNA Topoisomerases, EcoSal Plus 2009; doi:10.1128/ecosalplus.4.4.9
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 7
Figure 7

Domains in the ribbon diagram are indicated.

Reprinted from ( 21 ) with the permission of the publisher.

Citation: Evans-Roberts K, Maxwell A. 2009. DNA Topoisomerases, EcoSal Plus 2009; doi:10.1128/ecosalplus.4.4.9
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 8
Figure 8

The enzyme binds DNA and cleaves one strand, forming a 5′-phosphodiester linkage (black circle). The complementary strand is passed through the gap and into the central cavity of the enzyme. The nick is resealed, and the strand is released.

Reprinted from ( 11 ) with the permission of the publisher.

Citation: Evans-Roberts K, Maxwell A. 2009. DNA Topoisomerases, EcoSal Plus 2009; doi:10.1128/ecosalplus.4.4.9
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 9
Figure 9

(a) ATPase domain with ADPNP (in blue) ( 60 ). (b) The 92-kDa fragment (amino acids 410 to 1202) ( 57 ).

Panel a is reprinted from the ( 60 ); panel b is reprinted from with the permission of the publisher.

Citation: Evans-Roberts K, Maxwell A. 2009. DNA Topoisomerases, EcoSal Plus 2009; doi:10.1128/ecosalplus.4.4.9
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 10
Figure 10

ADPNP is depicted in stick form near the topoisomerase of the molecule. Reprinted from ( 83 ).

Citation: Evans-Roberts K, Maxwell A. 2009. DNA Topoisomerases, EcoSal Plus 2009; doi:10.1128/ecosalplus.4.4.9
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 11a
Figure 11a

Citation: Evans-Roberts K, Maxwell A. 2009. DNA Topoisomerases, EcoSal Plus 2009; doi:10.1128/ecosalplus.4.4.9
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 11b
Figure 11b

Citation: Evans-Roberts K, Maxwell A. 2009. DNA Topoisomerases, EcoSal Plus 2009; doi:10.1128/ecosalplus.4.4.9
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 12
Figure 12

GyrA consists of an N-terminal 59-kDa domain and a C-terminal 35-kDa domain. The QRDR and active-site Tyr are marked. The GyrB subunit consists of an N-terminal 43-kDa domain and a C-terminal 47-kDa domain.

Citation: Evans-Roberts K, Maxwell A. 2009. DNA Topoisomerases, EcoSal Plus 2009; doi:10.1128/ecosalplus.4.4.9
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 13
Figure 13

The protein structure is shown as ribbons, and ADPNP is shown as a space-filling representation.

Citation: Evans-Roberts K, Maxwell A. 2009. DNA Topoisomerases, EcoSal Plus 2009; doi:10.1128/ecosalplus.4.4.9
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 14
Figure 14

The protein structure is shown as ribbons, with the active-site tyrosines shown as space-filling representations.

Citation: Evans-Roberts K, Maxwell A. 2009. DNA Topoisomerases, EcoSal Plus 2009; doi:10.1128/ecosalplus.4.4.9
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 15
Figure 15

(a) The protein structure is shown as ribbons, with each of the six blades being a different color. (b) Representation of the β-pinwheel. One strand is highlighted in red.

Adapted from the ( 87 ) with the permission of the publisher.

Citation: Evans-Roberts K, Maxwell A. 2009. DNA Topoisomerases, EcoSal Plus 2009; doi:10.1128/ecosalplus.4.4.9
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 16
Figure 16

(a) The GyrA59 structure ( 86 ) is shown in blue, with the active-site tyrosines shown in yellow as space-filling representations. The GyrA59 carboxy termini are colored green. A model of the C-terminal domain ( 87 ) is shown as orange ribbons and is attached to GyrA59 by a linker. (b) The model of GyrB is shown in grey. The GyrB43 structure ( 104 ) is shown as blue ribbons. The TOPRIM region ( 57 ), tail 1, and tail 2 are shown as red, purple, and green ribbons, respectively.

Citation: Evans-Roberts K, Maxwell A. 2009. DNA Topoisomerases, EcoSal Plus 2009; doi:10.1128/ecosalplus.4.4.9
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 17
Figure 17

The domains are colored as follows: GyrB N-terminal domain, yellow; GyrB C-terminal domain, orange; GyrA N-terminal domain, dark blue; and GyrA C-terminal domain, light blue. The G and T DNA segments are colored green and red, respectively. (1 and 2) The G segment binds across GyrA, and the GyrA C-terminal domain wraps the DNA to present the T segment. (2 and 3) ATP is bound, which closes the GyrB clamp. (3 and 4) The G segment is cleaved, and the T segment passes through. (4 and 5) The T segment exits through the bottom gate, and the G segment is religated. (5 and 2) The hydrolysis of ATP resets the enzyme.

Reprinted from ( 129 ) with the permission of the publisher.

Citation: Evans-Roberts K, Maxwell A. 2009. DNA Topoisomerases, EcoSal Plus 2009; doi:10.1128/ecosalplus.4.4.9
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 18
Figure 18

Citation: Evans-Roberts K, Maxwell A. 2009. DNA Topoisomerases, EcoSal Plus 2009; doi:10.1128/ecosalplus.4.4.9
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 19
Figure 19

Part of the N-terminal GyrB structure is shown, with ADPNP in red and novobiocin in blue ( 149 ).

Citation: Evans-Roberts K, Maxwell A. 2009. DNA Topoisomerases, EcoSal Plus 2009; doi:10.1128/ecosalplus.4.4.9
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 20
Figure 20

Nalidixic acid and oxolinic acid are examples of older acidic quinolones. Ciprofloxacin and norfloxacin are examples of the amphoteric fluoroquinolones (expanded-spectrum compounds).

Citation: Evans-Roberts K, Maxwell A. 2009. DNA Topoisomerases, EcoSal Plus 2009; doi:10.1128/ecosalplus.4.4.9
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 21
Figure 21

Citation: Evans-Roberts K, Maxwell A. 2009. DNA Topoisomerases, EcoSal Plus 2009; doi:10.1128/ecosalplus.4.4.9
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 22a
Figure 22a

Citation: Evans-Roberts K, Maxwell A. 2009. DNA Topoisomerases, EcoSal Plus 2009; doi:10.1128/ecosalplus.4.4.9
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 22b
Figure 22b

Citation: Evans-Roberts K, Maxwell A. 2009. DNA Topoisomerases, EcoSal Plus 2009; doi:10.1128/ecosalplus.4.4.9
Permissions and Reprints Request Permissions
Download as Powerpoint

Tables

Generic image for table
TABLE 1.

Key properties of different topoisomerases

Citation: Evans-Roberts K, Maxwell A. 2009. DNA Topoisomerases, EcoSal Plus 2009; doi:10.1128/ecosalplus.4.4.9
Generic image for table
TABLE 2.

Drugs and toxins that target bacterial DNA gyrase (and topo IV)

Citation: Evans-Roberts K, Maxwell A. 2009. DNA Topoisomerases, EcoSal Plus 2009; doi:10.1128/ecosalplus.4.4.9

Supplemental Material

No supplementary material available for this content.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error