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Conformational changes in E. coli DNA topoisomerase I

Nature Structural Biology volume 6, pages 918–922 (1999)Cite this article

Abstract

DNA topoisomerases are the enzymes responsible for maintaining the topological states of DNA. In order to change the topology of DNA, topoisomerases pass one or two DNA strands through transient single or double strand breaks in the DNA phosphodiester backbone. It has been proposed that both type IA and type II enzymes change conformation dramatically during the reaction cycle in order to accomplish these transformations. In the case of Escherichia coli DNA topoisomerase I, it has been suggested that a 30 kDa fragment moves away from the rest of the protein to create an entrance into the central hole in the protein. Structures of the 30 kDa fragment reveal that indeed this fragment can change conformation significantly. The fragment is composed of two domains, and while the domains themselves remain largely unchanged, their relative arrangement can change dramatically.

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Figure 1: Structure of the 30 kDa fragment of E. coli DNA topoisomerase I in different environments and conformations.
Figure 2: Stereo view of the structure of the 30 kDa fragment of E. coli DNA topoisomerase I.
Figure 3: Stereo views of the active site region.
Figure 4: Model of the conformational changes in E. coli DNA topoisomerase I during the catalytic cycle based on the structures of the 67 kDa and the 30 kDa fragments.

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Acknowledgements

We thank past and present members of the laboratory and A. Changela, R. DiGate, L. Godley, M. Gwynn, T. Jardetzky, K. Perry, X. Qiu, A. Rosenzweig, A. Tackle, J. Widom and X. Yang, for help, comments and suggestions. We thank BNLS, CHESS, DND-CAT, ELETTRA and SSRL for access to their beamlines and help during data collection. We thank M. Blum of MAR USA for the use of the MAR CCD detector for experiments at BNLS. This work was supported by the NIH and by SmithKline Beecham Pharmaceuticals. Portions of this work were performed at the DuPont-Northwestern-Dow Collaborative Access Team (DND-CAT) Synchrotron Research Center at the Advanced Photon Source. DND-CAT is supported by DuPont, Dow, NSF and the State of Illinois. Use of the Advanced Photon Source was supported by the DOE.

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Author notes

  1. Hadar Feinberg

    Present address: Department of Structural Biology, Stanford University School of Medicine, Fairchild Building, Stanford, California, 94305-5400, USA

  2. Christopher D. Lima

    Present address: Department of Biochemistry, Weil Medical College of Cornell University, 1300 York Avenue, New York, New York, 10021, USA

Authors and Affiliations

  1. Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, 2153 Sheridan Road, Evanston, 60208, Illinois, USA

    Hadar Feinberg, Christopher D. Lima & Alfonso Mondragón

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  1. Hadar Feinberg
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Correspondence to Alfonso Mondragón.

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Feinberg, H., Lima, C. & Mondragón, A. Conformational changes in E. coli DNA topoisomerase I. Nat Struct Mol Biol 6, 918–922 (1999). https://doi.org/10.1038/13283

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