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Structure of a quinolone-stabilized cleavage complex of topoisomerase IV from Klebsiella pneumoniae and comparison with a related Streptococcus pneumoniae complex

DOI: 10.1107/S2059798316001212 DOI Help

Authors: Dennis Veselkov (King's College London) , Ivan Laponogov (King's College London, University of London) , Xiao-su Pan (University of London) , Jogitha Selvarajah (St George's University of London) , Galyna Skamrova (King's College London) , Arthur Branstrom (PTC Therapeutics Inc.) , Jana Narasimhan (PTC Therapeutics Inc.) , Josyula V. N. Vara Prasad (PTC Therapeutics Inc.) , L. Mark Fisher ( , Mark Sanderson (Kings College London)
Co-authored by industrial partner: Yes

Type: Journal Paper
Journal: Acta Crystallographica Section D Structural Biology , VOL 72 , PAGES 488 - 496

State: Published (Approved)
Published: April 2016
Diamond Proposal Number(s): 1220

Open Access Open Access

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 angstrom 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.

Journal Keywords: Klebsiella pneumoniae; cleavage complex; quinolone; levofloxacin; topoisomerase IV; DNA binding; isomerase; isomerase-DNA complex; topoisomerases; Gram-negative complexes; X-ray crystallography; protein-DNA-drug complexes

Subject Areas: Biology and Bio-materials, Medicine, Chemistry

Instruments: I02-Macromolecular Crystallography , I03-Macromolecular Crystallography , I04-1-Macromolecular Crystallography (fixed wavelength) , I04-Macromolecular Crystallography , I24-Microfocus Macromolecular Crystallography