title: Structure of a quinolone-stabilized cleavage complex of topoisomerase IV from Klebsiella pneumoniae and comparison with a related Streptococcus pneumoniae complex.
abstract: Klebsiella pneumoniae is a Gram-negative bacterium that is responsible for a range of common infections, including pulmonary pneumonia, bloodstream infections and meningitis. Certain strains of Klebsiella have become highly resistant to antibiotics. Despite the vast amount of research carried out on this class of bacteria, the molecular structure of its topoisomerase IV, a type II topoisomerase essential for catalysing chromosomal segregation, had remained unknown. In this paper, the structure of its DNA-cleavage complex is reported at 3.35 Å resolution. The complex is comprised of ParC breakage-reunion and ParE TOPRIM domains of K. pneumoniae topoisomerase IV with DNA stabilized by levofloxacin, a broad-spectrum fluoroquinolone antimicrobial agent. This complex is compared with a similar complex from Streptococcus pneumoniae, which has recently been solved.
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, 3rd Floor, New Hunt's House, Guy's Campus, London SE1 1UL, England.
authors.forename: Dennis A
authors.initials: DA
authors.lastname: Veselkov
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, 3rd Floor, New Hunt's House, Guy's Campus, London SE1 1UL, England.
authors.forename: Ivan
authors.initials: I
authors.lastname: Laponogov
authors.affiliation: Cardiovascular and Cell Sciences Research Institute, St George's, University of London, Cranmer Terrace, London SW17 0RE, England.
authors.forename: Xiao-Su
authors.initials: XS
authors.lastname: Pan
authors.affiliation: Cardiovascular and Cell Sciences Research Institute, St George's, University of London, Cranmer Terrace, London SW17 0RE, England.
authors.forename: Jogitha
authors.initials: J
authors.lastname: Selvarajah
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, 3rd Floor, New Hunt's House, Guy's Campus, London SE1 1UL, England.
authors.forename: Galyna B
authors.initials: GB
authors.lastname: Skamrova
authors.affiliation: PTC Therapeutics Inc., 100 Corporate Court, South Plainfield, NJ 07080, USA.
authors.forename: Arthur
authors.initials: A
authors.lastname: Branstrom
authors.affiliation: PTC Therapeutics Inc., 100 Corporate Court, South Plainfield, NJ 07080, USA.
authors.forename: Jana
authors.initials: J
authors.lastname: Narasimhan
authors.affiliation: PTC Therapeutics Inc., 100 Corporate Court, South Plainfield, NJ 07080, USA.
authors.forename: Josyula V N Vara
authors.initials: JV
authors.lastname: Prasad
authors.affiliation: Cardiovascular and Cell Sciences Research Institute, St George's, University of London, Cranmer Terrace, London SW17 0RE, England.
authors.forename: L Mark
authors.initials: LM
authors.lastname: Fisher
authors.affiliation: Randall Division of Cell and Molecular Biophysics, King's College London, 3rd Floor, New Hunt's House, Guy's Campus, London SE1 1UL, England.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Sanderson
mesh_terms: D001426:Bacterial Proteins / Q000737:chemistry*; D027101:DNA Topoisomerase IV / Q000737:chemistry*; D004269:DNA, Bacterial / Q000737:chemistry; D007711:Klebsiella pneumoniae / Q000201:enzymology*; D015363:Quinolones / Q000737:chemistry*; D013296:Streptococcus pneumoniae / Q000201:enzymology*
chemical_list: D001426:Bacterial Proteins; D004269:DNA, Bacterial; D015363:Quinolones; D027101:DNA Topoisomerase IV
keywords: DNA binding; Gram-negative complexes; Klebsiella pneumoniae; X-ray crystallography; cleavage complex; isomerase; isomerase–DNA complex; levofloxacin; protein–DNA–drug complexes; quinolone; topoisomerase IV; topoisomerases