Scheme. 1.

Reaction pathways relevant to INH activation by KatG. Rates of Fe(IV) = OPor⁺· formation using PAA (7.4 × 10⁴ m⁻¹ s⁻¹ for KatG[S315G]; 3.0 × 10⁴ m⁻¹ s⁻¹ for WT KatG) and decay of heme intermediates back to resting enzyme (40 s, KatG[S315G]; 80 s, WT KatG) are shown. Results suggest that increased rate or efficiency of single electron reactions with peroxide(s) leads to a decreased activation (oxidation) of INH and therefore to decreased IN-NAD adduct formation, ultimately producing drug resistance in strains harboring the S315G mutation.