Gyrase, bacterial

The 3-amino-4,7-dihydroxy-coumarin moiety is a core unit of this family of compounds. The amino group of coumarin scaffold is further decorated with derivatives of pyrrole or benzoic acid moieties. Also, branched deoxysugar 5-C-methyl-L-rhamnose (noviose) is installed onto one of the hydroxyls of the coumarin. Clorobiocin 67 and novobiocin 68 can be considered prototypical aminocoumarins. These molecules are potent inhibitors of bacterial gyrase and topo-isomerase IV and 68 is used to treat human infections. Several works also showed that analogs of 68, in combination with other drugs, can improve the chemotherapy of certain tumors [121]. 

Bacterial DNA topoisomerase I II Yeast DNA topoisomerase III DNA topoisomerase Ilia and III Mammalian DNA topoisomerase Ilia and III Vaccinia and Pox vims monomeric topo I Kinetoplastida bi-subunit topoisomerase I Mammalian mitochondrial topoisomerase I Eukaryotic monomeric topoisomerase I Bacterial gyrase, DNA topoisomerase IV Phage T4 DNA topoismnerase Yeast DNA topoisomerase II Drosophila DNA topoisomerase II Mammalian DNA topoisomerase Ha and lip Sulfolobus shibate DNA topoisomerase VI (subunit A honwiogous to yeast SP011)... 

Gyrase is another term for bacterial topoisomerase II. The enzyme consists of two A and two B subunits and is responsible for the negative supercoiling of the bacterial DNA. Negative supercoiling makes the bacterial DNA more compact and also more readily accessible to enzymes that cause duplication and transcription of the DNA to RNA. 

The answer is d. (Hardman, pp 1065—1067. Katzung, p 797.) Bacterial DNA gyrase is composed of four subunits, and levofloxacin binds to the strand-cutting subunits, inhibiting their activity... 

Fig. 19.3 Flow chart of 3D structure-based biased needle screening as applied to the bacterial enzyme, gyrase.

The quinoline antibiotics act by inhibiting bacterial DNA gyrase. These include Cipro, Levaquin, Floxacin, and Floxin. 

DNA gyrase a bacterial enzyme that catalyzes the unwinding of DNA the molecular target of the quinolone antibiotics. 

Gradisar H, Pristovsek P, Placer A, Jerala R. (2007) Green tea catechins inhibit bacterial DNA gyrase by interaction with its ATP binding site. 7 Med Chem 50 264-271. 

The quinolones are good general antibiotics for systemic infections, and they are particularly useful for urinary tract infections because high concentrations are excreted into the urine. The mode of action involves interference with DNA replication by inhibiting DNA gyrase, a bacterial enzyme related to mammalian topoisomerases that breaks and reseals double-stranded DNA during replication. 

Substances known as intercalators, such as rifamycin and actinomycin D (bottom) are deposited in the DNA double helix and thereby interfere with replication and transcription (B). As DNA is the same in all cells, intercalating antibiotics are also toxic for eukaryotes, however. They are therefore only used as cytostatic agents (see p. 402). Synthetic inhibitors of DNA topoisomerase II (see p. 240), known as gyrase inhibitors (center), restrict replication and thus bacterial reproduction. 

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