Crystallization and initial crystallographic analysis of covalent DNA-cleavage complexes of Staphyloccocus aureus DNA gyrase with QPT-1, moxifloxacin and etoposide
| Autor: | Claus Spitzfaden, Paul Homes, Andrew P. Fosberry, Jianzhong Huang, Martin Hibbs, Michael N. Gwynn, Anthony Shillings, Alexandre Wohlkonig, Andrew J. Theobald, Pan F. Chan, Velupillai Srikannathasan, Onkar M. P. Singh, Benjamin D. Bax |
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| Přispěvatelé: | Department of Bio-engineering Sciences, Structural Biology Brussels |
| Jazyk: | angličtina |
| Rok vydání: | 2015 |
| Předmět: |
Staphylococcus aureus
Etoposide/chemistry crystallization Molecular Sequence Data Moxifloxacin Biophysics medicine.disease_cause Crystallography X-Ray Biochemistry DNA gyrase Heterocyclic Compounds 4 or More Rings law.invention Research Communications chemistry.chemical_compound Structural Biology law Genetics medicine Spiro Compounds DNA Gyrase/chemistry Crystallization DNA Cleavage Etoposide Heterocyclic Compounds 4 or More Rings/chemistry biology Base Sequence Topoisomerase Spiro Compounds/chemistry Staphylococcus aureus/enzymology Condensed Matter Physics biology.organism_classification Fluoroquinolones/chemistry Crystallography chemistry Covalent bond DNA Gyrase biology.protein DNA Bacteria medicine.drug Fluoroquinolones |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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