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Publication Abstract from PubMed

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 A 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 A 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.

Trapping of the transport-segment DNA by the ATPase domains of a type II topoisomerase.,Laponogov I, Pan XS, Veselkov DA, Skamrova GB, Umrekar TR, Fisher LM, Sanderson MR Nat Commun. 2018 Jul 3;9(1):2579. doi: 10.1038/s41467-018-05005-x. PMID:29968711^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.