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Replacement of ParC 4 Helix with That of GyrA Increases the Stability and Cytotoxicity of Topoisomerase IV-Quinolone-DNA Ternary Complexes

Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455

Received 1 September 2003/ Returned for modification 13 October 2003/ Accepted 30 October 2003

Replacement of the 4 helix of ParC with that of GyrA increased the stability of topoisomerase IV-quinolone-DNA ternary complexes. This mutant topoisomerase IV-mediated cell killing was more efficient than topoisomerase IV-mediated cell killing in Escherichia coli. Thus, the 4 helix plays critical roles in determining the stability and the cytotoxicity of ternary complexes.

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