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Biochem Pharmacol. 2012 Oct 1;84(7):900-4. doi: 10.1016/j.bcp.2012.07.007. Epub 2012 Jul 20.

Allosteric inhibition of the DNA-dependent ATPase activity of Escherichia coli DNA gyrase by a representative of a novel class of inhibitors.

Author information

1
Bioscience Department, Infection Innovative Medicines, AstraZeneca R&D Boston, Waltham, MA 02451, USA. adam.shapiro@astrazeneca.com

Abstract

A novel class of bacterial DNA gyrase inhibitors has been shown previously to form a ternary complex with DNA and gyrase in a site distinct from the fluoroquinolone and ATP binding sites and does not cause double-strand-cleaved complex stabilization like fluoroquinolones. We show that, unlike fluoroquinolones, a representative compound inhibits DNA-dependent ATP hydrolysis by Escherichia coli gyrase and also blocks cleaved complex stabilization by ciprofloxacin. Conversely, ciprofloxacin blocks ATPase inhibition by the novel compound. We conclude that the compound acts allosterically to inhibit ATP binding or hydrolysis and interferes with the gyrase catalytic cycle at a different point than ciprofloxacin.

PMID:
22820247
DOI:
10.1016/j.bcp.2012.07.007
[Indexed for MEDLINE]

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