Trapping of the transport-segment DNA by the ATPase domains of a type II topoisomerase

Ivan Laponogov, Xiao Su Pan, Dennis A. Veselkov, Galyna B. Skamrova, Trishant R. Umrekar, L. Mark Fisher, Mark R. Sanderson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

19 Citations (Scopus)
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Type II topoisomerases alter DNA topology to control DNA supercoiling and chromosome segregation and are targets of clinically important anti-infective and anticancer therapeutics. They act as ATP-operated clamps to trap a DNA helix and transport it through a transient break in a second DNA. Here, we present the first X-ray crystal structure solved at 2.83 Å of a closed clamp complete with trapped T-segment DNA obtained by co-crystallizing the ATPase domain of S. pneumoniae topoisomerase IV with a nonhydrolyzable ATP analogue and 14-mer duplex DNA. The ATPase dimer forms a 22 Å protein hole occupied by the kinked DNA bound asymmetrically through positively charged residues lining the hole, and whose mutagenesis impacts the DNA decatenation, DNA relaxation and DNA-dependent ATPase activities of topo IV. These results and a side-bound DNA-ParE structure help explain how the T-segment DNA is captured and transported by a type II topoisomerase, and reveal a new enzyme-DNA interface for drug discovery.

Original languageEnglish
Article number2579
JournalNature Communications
Issue number1
Early online date3 Jul 2018
Publication statusE-pub ahead of print - 3 Jul 2018


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