Table 1

Properties of simocyclinone- and quinolone-resistant GyrA mutants. NA indicates not applicable. Mutant H78A is not active; KD for simocyclinone is ~10 times that of wild type. S83W data is from (19).

GyrA mutationRelative IC50 (supercoiling)
SimocyclinoneCiprofloxacin
Wild type1 (0.6 μM)*1 (0.7 μM)*
Mutations in the simocyclinone-binding site
Aminocoumarin-binding pocket mutations
Aminocoumarin-binding pocket mutations
H45A9.12.2
R91A201.1
Polyketide-binding pocket mutations
H78ANANA
H80A2302.8
Mutations in both pockets
H45A and H80A>5002.3
Mutations in the quinolone-resistance–determining region of GyrA
G81D4024
S83W1030
A84P3828
D87A7.25.2
D87Y5730
S83A and D87A8.312

*Actual IC50 values are given in parentheses.