Competition between ciprofloxacin and 8-methyl-3′-(AM)P-dione
and the effects of ciprofloxacin on DNA relaxation. The ability of
0–200 μM ciprofloxacin to compete with 10 μM 8-methyl-3′-(AM)P-dione
for ParCS80L (S80L, blue), ParCS80I (S80I, red),
ParCS80F (S80F, green), and ParCE84K (E84K,
yellow) E. coli topoisomerase IV was determined using
DNA cleavage assays (left). Both drugs were added to reaction mixtures
simultaneously. For ParCS80L, the level of cleavage seen
in the presence of ciprofloxacin alone was used as a baseline and
subtracted from the total observed in the presence of both drugs.
The level of DNA cleavage observed in the presence of only the quinazolinedione
was set to 1.0 to facilitate direct comparisons. The effects of ciprofloxacin
on the relaxation activities of wild-type (WT, black), ParCS80L (S80L, blue), ParCS80I (S80I, red), ParCS80F (S80F, green), and ParCE84K (E84K, yellow) topoisomerase
IV are shown at the right. Wild-type, ParCS80L, and ParCS80F relaxation reactions were stopped at 10 min, ParCS80I reactions at 20 min, and ParCE84K reactions
at 30 min to account for the different baseline DNA relaxation rates
of the different enzymes. The amount of relaxed DNA observed in the
absence of drug (“0” point) was set to 100% to facilitate
direct comparisons. Error bars represent the standard deviation of
three or more independent experiments.