title: Structural insight into the quinolone-DNA cleavage complex of type IIA topoisomerases.
abstract: Type II topoisomerases alter DNA topology by forming a covalent DNA-cleavage complex that allows DNA transport through a double-stranded DNA break. We present the structures of cleavage complexes formed by the Streptococcus pneumoniae ParC breakage-reunion and ParE TOPRIM domains of topoisomerase IV stabilized by moxifloxacin and clinafloxacin, two antipneumococcal fluoroquinolones. These structures reveal two drug molecules intercalated at the highly bent DNA gate and help explain antibacterial quinolone action and resistance.
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, University of London, London, UK.
authors.forename: Ivan
authors.initials: I
authors.lastname: Laponogov
authors.forename: Maninder K
authors.initials: MK
authors.lastname: Sohi
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Veselkov
authors.forename: Xiao-Su
authors.initials: XS
authors.lastname: Pan
authors.forename: Ritica
authors.initials: R
authors.lastname: Sawhney
authors.forename: Andrew W
authors.initials: AW
authors.lastname: Thompson
authors.forename: Katherine E
authors.initials: KE
authors.lastname: McAuley
authors.forename: L Mark
authors.initials: LM
authors.lastname: Fisher
authors.forename: Mark R
authors.initials: MR
authors.lastname: Sanderson
mesh_terms: D000890:Anti-Infective Agents / Q000494:pharmacology; D000951:Antigens, Neoplasm / Q000737:chemistry*; D001372:Aza Compounds / Q000494:pharmacology; D004247:DNA / Q000737:chemistry*; D027101:DNA Topoisomerase IV / Q000378:metabolism; D004250:DNA Topoisomerases, Type II / Q000737:chemistry*; D004268:DNA-Binding Proteins / Q000737:chemistry*; D024881:Drug Resistance, Bacterial; D024841:Fluoroquinolones / Q000494:pharmacology; D008958:Models, Molecular; D008968:Molecular Conformation; D000077266:Moxifloxacin; D011485:Protein Binding; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D011804:Quinolines / Q000494:pharmacology; D015363:Quinolones / Q000737:chemistry*; D013296:Streptococcus pneumoniae / Q000378:metabolism*
chemical_list: D000890:Anti-Infective Agents; D000951:Antigens, Neoplasm; D001372:Aza Compounds; D004268:DNA-Binding Proteins; D024841:Fluoroquinolones; D011804:Quinolines; D015363:Quinolones; C057477:clinafloxacin; D004247:DNA; D027101:DNA Topoisomerase IV; D004250:DNA Topoisomerases, Type II; D000077266:Moxifloxacin