Fluoroquinolones stimulate the DNA cleavage activity of topoisomerase IV by promoting the binding of Mg(2+) to the second metal binding site.

ABSTRACT:

Background

Fluoroquinolones target bacterial type IIA topoisomerases, DNA gyrase and topoisomerase IV (Topo IV). Fluoroquinolones trap a topoisomerase-DNA covalent complex as a topoisomerase-fluoroquinolone-DNA ternary complex and ternary complex formation is critical for their cytotoxicity. A divalent metal ion is required for type IIA topoisomerase-catalyzed strand breakage and religation reactions. Recent studies have suggested that type IIA topoisomerases use two metal ions, one structural and one catalytic, to carry out the strand breakage reaction.

Methods

We conducted a series of DNA cleavage assays to examine the effects of fluoroquinolones and quinazolinediones on Mg(2+)-, Mn(2+)-, or Ca(2+)-supported DNA cleavage activity of Escherichia coli Topo IV.

Results

SUBMITTER: Oppegard LM 

PROVIDER: S-EPMC4720527 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature