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

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...

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Published in:Acta crystallographica. Section D, Structural biology Structural biology, 2016-04, Vol.72 (4), p.488-496
Main Authors: Veselkov, Dennis A., Laponogov, Ivan, Pan, Xiao-Su, Selvarajah, Jogitha, Skamrova, Galyna B., Branstrom, Arthur, Narasimhan, Jana, Prasad, Josyula V. N. Vara, Fisher, L. Mark, Sanderson, Mark R.
Format: Article
Language:English
Subjects:
Bacterial Proteins - chemistry
cleavage complex
DNA binding
DNA Topoisomerase IV - chemistry
DNA, Bacterial - chemistry
Gram-negative complexes
isomerase
isomerase-DNA complex
Klebsiella pneumoniae
Klebsiella pneumoniae - enzymology
levofloxacin
protein-DNA-drug complexes
quinolone
Quinolones - chemistry
Research Papers
Streptococcus pneumoniae - enzymology
topoisomerase IV
topoisomerases
X-ray crystallography
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Summary: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. Crystal structures of the cleavage complexes of topoisomerase IV from Gram‐negative (K. pneumoniae) and Gram‐positive (S. pneumoniae) bacterial pathogens stabilized by the clinically important antibacterial drug levofloxacin are presented, analysed and compared. For K. pneumoniae, this is the first high‐resolution cleavage complex structure to be reported.
ISSN:2059-7983
2059-7983
DOI:10.1107/S2059798316001212