Exploiting bacterial DNA gyrase as a drug target: current state and perspectives.
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TLDR
Known gyrase-specific drugs and toxins are reviewed and the prospects for developing new antibacterials targeted to this enzyme are assessed.Abstract:
DNA gyrase is a type II topoisomerase that can introduce negative supercoils into DNA at the expense of ATP hydrolysis. It is essential in all bacteria but absent from higher eukaryotes, making it an attractive target for antibacterials. The fluoroquinolones are examples of very successful gyrase-targeted drugs, but the rise in bacterial resistance to these agents means that we not only need to seek new compounds, but also new modes of inhibition of this enzyme. We review known gyrase-specific drugs and toxins and assess the prospects for developing new antibacterials targeted to this enzyme.read more
Citations
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Targeting a highly conserved domain in bacterial histidine kinases to generate inhibitors with broad spectrum activity
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New N-phenyl-4,5-dibromopyrrolamides as DNA gyrase B inhibitors
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TL;DR: Results indicate that for potent inhibition of DNA gyrase, a combination of polar groups on the carboxylic end of the molecule and substituents that reach into the 'lipophilic floor' of the enzyme is required.
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Use of in vivo induced technology to identify antigens expressed by Photobacterium damselae subsp. piscicida during infection of Senegalese sole (Solea senegalensis)
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Designing type II topoisomerase inhibitors: A molecular modeling approach.
TL;DR: Diverse modes of intervention are described including, inhibition of their ATPase function, stabilization of the cleavage complex or prevention of DNA strand hydrolysis, and efforts to circumvent the effect of non-susceptible strains by the design of new drugs based on existing ones.
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In silico study directed towards identification of the key structural features of GyrB inhibitors targeting MTB DNA gyrase: HQSAR, CoMSIA and molecular dynamics simulations.
Pharit Kamsri,Auradee Punkvang,Supa Hannongbua,Khomson Suttisintong,Prasat Kittakoop,Prasat Kittakoop,James Spencer,Adrian J. Mulholland,Pornpan Pungpo +8 more
TL;DR: Key structural features and a structural concept for rational design of novel DNA gyrase inhibitors with improved biological activities against both enzyme and mycobacterial cell, and with good pharmacokinetic properties and drug safety profiles are provided.
References
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Journal ArticleDOI
DNA topoisomerases: structure, function, and mechanism.
TL;DR: Surprisingly, despite little or no sequence homology, both type IA and type IIA topoisomerases from prokaryotes and the typeIIA enzymes from eukaryotes share structural folds that appear to reflect functional motifs within critical regions of the enzymes.
Journal ArticleDOI
A Common Mechanism of Cellular Death Induced by Bactericidal Antibiotics
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How antibiotics kill bacteria: from targets to networks
TL;DR: The multilayered effects of drug–target interactions, including the essential cellular processes that are inhibited by bactericidal antibiotics and the associated cellular response mechanisms that contribute to killing are discussed.
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DNA topoisomerases and their poisoning by anticancer and antibacterial drugs.
TL;DR: This review focuses on the molecular and biochemical characteristics of topoisomerases and their inhibitors and discusses the common mechanism of action ofTopoisomerase poisons by interfacial inhibition and trapping of topisomerase cleavage complexes.
Journal ArticleDOI
Quinolone resistance from a transferable plasmid
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