1d6m Citations

The structure of Escherichia coli DNA topoisomerase III.

Structure 7 1373-83 (1999)
Cited: 38 times
EuropePMC logo PMID: 10574789



DNA topoisomerases are enzymes that change the topology of DNA. Type IA topoisomerases transiently cleave one DNA strand in order to pass another strand or strands through the break. In this manner, they can relax negatively supercoiled DNA and catenate and decatenate DNA molecules. Structural information on Escherichia coli DNA topoisomerase III is important for understanding the mechanism of this type of enzyme and for studying the mechanistic differences among different members of the same subfamily.


The structure of the intact and fully active E. coli DNA topoisomerase III has been solved to 3.0 A resolution. The structure shows the characteristic fold of the type IA topoisomerases that is formed by four domains, creating a toroidal protein. There is remarkable structural similarity to the 67 kDa N-terminal fragment of E. coli DNA topoisomerase I, although the relative arrangement of the four domains is significantly different. A major difference is the presence of a 17 amino acid insertion in topoisomerase III that protrudes from the side of the central hole and could be involved in the catenation and decatenation reactions. The active site is formed by highly conserved amino acids, but the structural information and existing biochemical and mutagenesis data are still insufficient to assign specific roles to most of them. The presence of a groove in one side of the protein is suggestive of a single-stranded DNA (ssDNA)-binding region.


The structure of E. coli DNA topoisomerase III resembles the structure of E. coli DNA topoisomerase I except for the presence of a positively charged loop that may be involved in catenation and decatenation. A groove on the side of the protein leads to the active site and is likely to be involved in DNA binding. The structure helps to establish the overall mechanism for the type IA subfamily of topoisomerases with greater confidence and expands the structural basis for understanding these proteins.

Articles - 1d6m mentioned but not cited (2)

  1. FoldMiner and LOCK 2: protein structure comparison and motif discovery on the web. Shapiro J, Brutlag D. Nucleic Acids Res. 32 W536-41 (2004)
  2. Computer-based screening of functional conformers of proteins. Montiel Molina HM, Millán-Pacheco C, Pastor N, del Rio G. PLoS Comput. Biol. 4 e1000009 (2008)

Reviews citing this publication (11)

  1. Molecular mechanism of double Holliday junction dissolution. Swuec P, Costa A. Cell Biosci 4 36 (2014)
  2. Topoisomerases and site-specific recombinases: similarities in structure and mechanism. Yang W. Crit. Rev. Biochem. Mol. Biol. 45 520-534 (2010)
  3. Structural studies of type I topoisomerases. Baker NM, Rajan R, Mondragón A. Nucleic Acids Res. 37 693-701 (2009)
  4. DNA topoisomerases: harnessing and constraining energy to govern chromosome topology. Schoeffler AJ, Berger JM. Q. Rev. Biophys. 41 41-101 (2008)
  5. Type IA topoisomerases: a simple puzzle? Viard T, de la Tour CB. Biochimie 89 456-467 (2007)
  6. Origin and evolution of DNA topoisomerases. Forterre P, Gribaldo S, Gadelle D, Serre MC. Biochimie 89 427-446 (2007)
  7. Structure, molecular mechanisms, and evolutionary relationships in DNA topoisomerases. Corbett KD, Berger JM. Annu Rev Biophys Biomol Struct 33 95-118 (2004)
  8. DNA manipulators: caught in the act. Changela A, Perry K, Taneja B, Mondragón A. Curr. Opin. Struct. Biol. 13 15-22 (2003)
  9. Covalent trapping of protein-DNA complexes. Verdine GL, Norman DP. Annu. Rev. Biochem. 72 337-366 (2003)
  10. DNA topoisomerases: structure, function, and mechanism. Champoux JJ. Annu. Rev. Biochem. 70 369-413 (2001)
  11. Mechanisms of DNA replication. Davey MJ, O'Donnell M. Curr Opin Chem Biol 4 581-586 (2000)

Articles citing this publication (25)

  1. Modular architecture of the bacteriophage T7 primase couples RNA primer synthesis to DNA synthesis. Kato M, Ito T, Wagner G, Richardson CC, Ellenberger T. Mol. Cell 11 1349-1360 (2003)
  2. Creating a dynamic picture of the sliding clamp during T4 DNA polymerase holoenzyme assembly by using fluorescence resonance energy transfer. Trakselis MA, Alley SC, Abel-Santos E, Benkovic SJ. Proc. Natl. Acad. Sci. U.S.A. 98 8368-8375 (2001)
  3. Identification of the SSB binding site on E. coli RecQ reveals a conserved surface for binding SSB's C terminus. Shereda RD, Reiter NJ, Butcher SE, Keck JL. J. Mol. Biol. 386 612-625 (2009)
  4. Mitotic chromosomes are constrained by topoisomerase II-sensitive DNA entanglements. Kawamura R, Pope LH, Christensen MO, Sun M, Terekhova K, Boege F, Mielke C, Andersen AH, Marko JF. J. Cell Biol. 188 653-663 (2010)
  5. Structure of a complex between E. coli DNA topoisomerase I and single-stranded DNA. Perry K, Mondragón A. Structure 11 1349-1358 (2003)
  6. Structural studies of E. coli topoisomerase III-DNA complexes reveal a novel type IA topoisomerase-DNA conformational intermediate. Changela A, DiGate RJ, Mondragón A. J. Mol. Biol. 368 105-118 (2007)
  7. A type IB topoisomerase with DNA repair activities. Belova GI, Prasad R, Kozyavkin SA, Lake JA, Wilson SH, Slesarev AI. Proc. Natl. Acad. Sci. U.S.A. 98 6015-6020 (2001)
  8. FoldMiner: structural motif discovery using an improved superposition algorithm. Shapiro J, Brutlag D. Protein Sci. 13 278-294 (2004)
  9. Identification of a unique domain essential for Escherichia coli DNA topoisomerase III-catalysed decatenation of replication intermediates. Li Z, Mondragón A, Hiasa H, Marians KJ, DiGate RJ. Mol. Microbiol. 35 888-895 (2000)
  10. Structural and mechanistic insight into Holliday-junction dissolution by topoisomerase IIIα and RMI1. Bocquet N, Bizard AH, Abdulrahman W, Larsen NB, Faty M, Cavadini S, Bunker RD, Kowalczykowski SC, Cejka P, Hickson ID, Thomä NH. Nat. Struct. Mol. Biol. 21 261-268 (2014)
  11. The role of the Zn(II) binding domain in the mechanism of E. coli DNA topoisomerase I. Ahumada A, Tse-Dinh YC. BMC Biochem. 3 13 (2002)
  12. The mechanism of type IA topoisomerase-mediated DNA topological transformations. Li Z, Mondragón A, DiGate RJ. Mol. Cell 7 301-307 (2001)
  13. Crystal structure of full length topoisomerase I from Thermotoga maritima. Hansen G, Harrenga A, Wieland B, Schomburg D, Reinemer P. J. Mol. Biol. 358 1328-1340 (2006)
  14. Adenosine 5'-O-(3-thio)triphosphate (ATPgammaS) promotes positive supercoiling of DNA by T. maritima reverse gyrase. Jungblut SP, Klostermeier D. J. Mol. Biol. 371 197-209 (2007)
  15. Bacterial topoisomerase I and topoisomerase III relax supercoiled DNA via distinct pathways. Terekhova K, Gunn KH, Marko JF, Mondragón A. Nucleic Acids Res. 40 10432-10440 (2012)
  16. A universal type IA topoisomerase fold. Duguet M, Serre MC, Bouthier de La Tour C. J. Mol. Biol. 359 805-812 (2006)
  17. Structural basis for suppression of hypernegative DNA supercoiling by E. coli topoisomerase I. Tan K, Zhou Q, Cheng B, Zhang Z, Joachimiak A, Tse-Dinh YC. Nucleic Acids Res. 43 11031-11046 (2015)
  18. Three-dimensional electron microscopy of the reverse gyrase from Sulfolobus tokodaii. Matoba K, Mayanagi K, Nakasu S, Kikuchi A, Morikawa K. Biochem. Biophys. Res. Commun. 297 749-755 (2002)
  19. Research Support, U.S. Gov't, P.H.S. A first view of the structure of a type IA topoisomerase with bound DNA. Champoux JJ. Trends Pharmacol. Sci. 23 199-201 (2002)
  20. Insights from the Structure of Mycobacterium tuberculosis Topoisomerase I with a Novel Protein Fold. Tan K, Cao N, Cheng B, Joachimiak A, Tse-Dinh YC. J. Mol. Biol. 428 182-193 (2016)
  21. Bacillus cereus DNA topoisomerase I and IIIalpha: purification, characterization and complementation of Escherichia coli TopoIII activity. Li Z, Hiasa H, DiGate R. Nucleic Acids Res. 33 5415-5425 (2005)
  22. The type IA topoisomerase catalytic cycle: A normal mode analysis and molecular dynamics simulation. Xiong B, Burk DL, Shen J, Luo X, Liu H, Shen J, Berghuis AM. Proteins 71 1984-1994 (2008)
  23. Single-molecule analysis uncovers the difference between the kinetics of DNA decatenation by bacterial topoisomerases I and III. Terekhova K, Marko JF, Mondragón A. Nucleic Acids Res. 42 11657-11667 (2014)
  24. Cloning and biochemical characterization of Staphylococcus aureus type IA DNA topoisomerase comprised of distinct five domains. Park JE, Kim HI, Park JW, Park JK, Lee JS. Arch. Biochem. Biophys. 508 78-86 (2011)
  25. Kinetic insights into the temperature dependence of DNA strand cleavage and religation by topoisomerase III from the hyperthermophile Sulfolobus solfataricus. Zhang J, Pan B, Li Z, Sheng Zhao X, Huang L. Sci Rep 7 5494 (2017)