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Crystallization and initial crystallographic analysis of covalent DNA-cleavage complexes ofStaphyloccocus aureusDNA gyrase with QPT-1, moxifloxacin and etoposide

Srikannathasan, Velupillai, Wohlkonig, Alexandre, Shillings, Anthony, Singh, Onkar, Chan, Pan F., Huang, Jianzhong, Gwynn, Michael N., Fosberry, Andrew P., Homes, Paul, Hibbs, Martin, Theobald, Andrew J., Spitzfaden, Claus and Bax, Benjamin 2015. Crystallization and initial crystallographic analysis of covalent DNA-cleavage complexes ofStaphyloccocus aureusDNA gyrase with QPT-1, moxifloxacin and etoposide. Acta Crystallographica Section F Structural Biology Communications 71 (10) , pp. 1242-1246. 10.1107/S2053230X15015290

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Abstract

Fluoroquinolone drugs such as moxifloxacin kill bacteria by stabilizing the normally transient double-stranded DNA breaks created by bacterial type IIA topoisomerases. Previous crystal structures of Staphylococcus aureus DNA gyrase with asymmetric DNAs have had static disorder (with the DNA duplex observed in two orientations related by the pseudo-twofold axis of the complex). Here, 20-base-pair DNA homoduplexes were used to obtain crystals of covalent DNA-cleavage complexes of S. aureus DNA gyrase. Crystals with QPT-1, moxifloxacin or etoposide diffracted to between 2.45 and 3.15 Å resolution. A G/T mismatch introduced at the ends of the DNA duplexes facilitated the crystallization of slightly asymmetric complexes of the inherently flexible DNA-cleavage complexes.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: International Union of Crystallography
ISSN: 2053-230X
Last Modified: 06 Jun 2018 11:19
URI: http://orca.cf.ac.uk/id/eprint/111271

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