Structural highlights
Function
[PARE_STRPN] Topoisomerase IV is essential for chromosome segregation. It relaxes supercoiled DNA. Performs the decatenation events required during the replication of a circular DNA molecule.[1] [2]
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.
See Also
References
- ↑ Laponogov I, Veselkov DA, Sohi MK, Pan XS, Achari A, Yang C, Ferrara JD, Fisher LM, Sanderson MR. Breakage-reunion domain of Streptococcus pneumoniae topoisomerase IV: crystal structure of a gram-positive quinolone target. PLoS ONE. 2007 Mar 21;2(3):e301. PMID:17375187 doi:10.1371/journal.pone.0000301
- ↑ Laponogov I, Pan XS, Veselkov DA, McAuley KE, Fisher LM, Sanderson MR. Structural basis of gate-DNA breakage and resealing by type II topoisomerases. PLoS One. 2010 Jun 28;5(6):e11338. PMID:20596531 doi:10.1371/journal.pone.0011338
- ↑ Laponogov I, Pan XS, Veselkov DA, Skamrova GB, Umrekar TR, Fisher LM, Sanderson MR. Trapping of the transport-segment DNA by the ATPase domains of a type II topoisomerase. Nat Commun. 2018 Jul 3;9(1):2579. doi: 10.1038/s41467-018-05005-x. PMID:29968711 doi:http://dx.doi.org/10.1038/s41467-018-05005-x
