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;
Bax, Benjamin D.
Crystallization and initial crystallographic analysis of covalent DNA-cleavage complexes of Staphyloccocus aureus DNA gyrase with QPT-1, moxifloxacin and etoposide
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Medientyp:
E-Artikel
Titel:
Crystallization and initial crystallographic analysis of covalent DNA-cleavage complexes of Staphyloccocus aureus DNA gyrase with QPT-1, moxifloxacin and etoposide
Beteiligte:
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;
Bax, Benjamin D.
Erschienen:
International Union of Crystallography (IUCr), 2015
Erschienen in:Acta Crystallographica Section F Structural Biology Communications
Beschreibung:
<jats:p>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 <jats:italic>Staphylococcus aureus</jats:italic> 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 <jats:italic>S. aureus</jats:italic> 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.</jats:p>