The DNA Gyrase-Quinolone Complex: ATP HYDROLYSIS AND THE MECHANISM OF DNA CLEAVAGE *
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TLDR
It is demonstrated that quinolone binding and drug-induced DNA cleavage are separate processes constituting two sequential steps in the mechanism of action of quinOLones on DNA gyrase, which is capable of ATP hydrolysis through an alternative pathway involving two different conformations of the enzyme.About:
This article is published in Journal of Biological Chemistry.The article was published on 1998-08-28 and is currently open access. It has received 111 citations till now. The article focuses on the topics: DNA gyrase & DNA supercoil.read more
Citations
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Book ChapterDOI
Type II DNA topoisomerases: Coupling directional DNA transport to ATP hydrolysis
TL;DR: This chapter describes the mechanism of the type II enzymes and focuses on the present knowledge about the way these enzymes couple adenosine triphosphate (ATP) binding and hydrolysis to the directional transport of one duplex DNA segment through a transient break in another.
Posted ContentDOI
Stochastic gene expression influences the selection of antibiotic resistance mutations
TL;DR: The findings show that stochastic gene expression is a key factor underlying efflux and enzymatic resistances and should be taken into consideration in future antibiotic research.
Posted ContentDOI
Mechanisms of antibiotic action shape the fitness landscapes of resistance mutations
Colin Hemez,Fabrizio Clarelli,Adam C. Palmer,Leonid Chindelevitch,Ted Cohen,Pia Abel zur Wiesch +5 more
TL;DR: It is suggested that antibiotic doses beyond this “secondary mutation selection window” could safeguard against the emergence of high-fitness resistant strains during treatment, and heterogeneous drug-target binding within a population enables resistant bacteria to evolve fitness-improving secondary mutations even when drug doses remain above the resistant strain's minimum inhibitory concentration.
Dissertation
Characterization and Molecular Mechanisms of Antimicrobial Resistance in Foodborne Pathogens
TL;DR: It appears that the most relevant genes with regards to the selection of fluoroquinolone resistance phenotypes among Salmonella are the AcrAB-tolC efflux pump and the gyrA portion of DNA gyrase gene, which could be transmitted through conjugation.
Journal Article
Bacterial dna gyrase is not the target of quinoline - based anti - tubercu losis compounds
TL;DR: It is found that although quinolones are the potent inhibitors of supercoiling activity of E. coli DNA gyrase,Quinolines are not the primary target of these synthetic quinoline compounds synthesized by us.
References
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Journal ArticleDOI
Theoretical aspects of DNA-protein interactions: co-operative and non-co-operative binding of large ligands to a one-dimensional homogeneous lattice.
TL;DR: The results indicate that the binding of any non-interacting ligand covering more than one lattice residue results in non- linear (convex downward) Scatchard plots, and the introduction of positive ligand-ligand co-operativity antagonizes this non-linearity, and eventually leads to plots of the opposite curvature.
Journal ArticleDOI
Nalidixic acid resistance: A second genetic character involved in DNA gyrase activity
TL;DR: The nalA locus is responsible for a second component needed for DNA gyrase activity in addition to the component determined by the previously described locus for resistance to novobiocin and coumermycin (cou), which appears to be involved in the nicking-closing activity required in the supercoiling reaction.
Journal ArticleDOI
Crystal structure of the breakage-reunion domain of DNA gyrase
Joo H. Morais Cabral,Andrew P. Jackson,Clare V. Smith,Nita Shikotra,Anthony Maxwell,Robert C. Liddington +5 more
TL;DR: The crystal structure of the breakage-reunion domain of DNA gyrase at 2.8 A resolution was presented in this paper, where it was shown that the two structures represent two principal conformations that participate in the enzymatic pathway.
Journal ArticleDOI
Mechanism of inhibition of DNA gyrase by quinolone antibacterials: a cooperative drug--DNA binding model.
Linus L. Shen,Lester A. Mitscher,Padam N. Sharma,T. J. O'Donnell,Daniel W. T. Chu,Curt S. Cooper,Terry J. Rosen,Andre G. Pernet +7 more
TL;DR: A cooperative quinolone-DNA binding model for the inhibition of DNA gyrase and the unique self-association phenomenon (from which the cooperativity is derived) of the drug molecules to fit the binding pocket with a high degree of flexibility is proposed.
Journal ArticleDOI
Energy coupling in DNA gyrase and the mechanism of action of novobiocin
TL;DR: It is postulate that ATP and App[NH]p are allosteric effectors of a conformational change of gyrase that leads to one round of supercoiling and that cyclic conformational changes accompanying alteration in nucleotide affinity also seem to be a common feature of energy transduction in other diverse processes including muscle contraction, protein synthesis, and oxidative phosphorylation.