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Involvement of topoisomerase IV and DNA gyrase as ciprofloxacin targets in Streptococcus pneumoniae
In both laboratory strains and clinical isolates, ParC mutations preceded those in GyrA, suggesting that topoisomersase IV is a primary topoisomerase target and gyrase is a secondary target for ciprofloxacin in S. pneumoniae. Expand
Targeting of DNA gyrase in Streptococcus pneumoniae by sparfloxacin: selective targeting of gyrase or topoisomerase IV by quinolones
  • X. Pan, L. Fisher
  • Biology, Medicine
  • Antimicrobial agents and chemotherapy
  • 1 February 1997
The targeting of gyrase by sparfloxacin in S. pneumoniae but of topoisomerase IV by ciprofloxACin indicates that target preference can be altered by changes in quinolone structure. Expand
Structural insight into the quinolone–DNA cleavage complex of type IIA topoisomerases
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 help explain antibacterial quinolone action and resistance. Expand
Structural Basis of Gate-DNA Breakage and Resealing by Type II Topoisomerases
X-ray crystallography is used to study sequential states in the formation and reversal of a DNA cleavage complex by topoisomerase IV from Streptococcus pneumoniae, the bacterial type II enzyme involved in chromosome segregation to suggest how a type II enzymes reseals DNA during its normal reaction cycle and illuminate aspects of drug arrest important for the development of new topoisomersase-targeting therapeutics. Expand
Cloning and characterization of the parC and parE genes of Streptococcus pneumoniae encoding DNA topoisomerase IV: role in fluoroquinolone resistance
The results suggest that DNA topoisomerase IV is an important target for fluoroquinolones in S. pneumoniae and establish this organism as a useful gram-positive system for resistance studies. Expand
Target specificity of the new fluoroquinolone besifloxacin in Streptococcus pneumoniae, Staphylococcus aureus and Escherichia coli.
Although mutant selection experiments indicated that gyrase is a primary target, further biochemical and genetic studies showed that besifloxacin has potent, relatively balanced activity against both essential DNA gyrases and topoisomerase IV targets in S. pneumoniae. Expand
Mycobacterium tuberculosis DNA Gyrase: Interaction with Quinolones and Correlation with Antimycobacterial Drug Activity
The quinolone structure-activity relationship demonstrated here shows that C-8, the C-7 ring, theC-6 fluorine, and the N-1 cyclopropyl substituents are desirable structural features in targeting M. tuberculosis gyrase. Expand
Structure of an ‘open’ clamp type II topoisomerase-DNA complex provides a mechanism for DNA capture and transport
The structure shows the molecular conformations of all three gates at 3.7 Å, the highest resolution achieved for the full complex to date, and illuminates the mechanism of DNA capture and transport by a type II topoisomerase. Expand
Trapping of the transport-segment DNA by the ATPase domains of a type II topoisomerase
The first X-ray crystal structure solved at 2.83 Å of a closed clamp complete with trapped T-segment DNA obtained by co-crystallizing the ATPase domain of S. pneumoniae topoisomerase IV is presented, and a side-bound DNA-ParE structure help explain how the T- Segment DNA is captured and transported by a type II topoisomersase, and reveal a new enzyme–DNA interface for drug discovery. Expand
Probing the Differential Interactions of Quinazolinedione PD 0305970 and Quinolones with Gyrase and Topoisomerase IV
Evidence is presented for Streptococcus pneumoniae gyrase and topo IV that PD 0305970 and quinolones interact differently with the enzyme breakage-reunion and Toprim domains, DNA, and Mg2+-four components that are juxtaposed in the topoisomerase cleavage complex to effect DNA scission. Expand