The role of Mn(II)-peroxidase activity of mycobacterial catalase- peroxidase in activation of the antibiotic isoniazid

Abstract

The catalase-peroxidase of Mycobacteria smegmatis exhibits Mn(II)- peroxidase activity characterized by a low K(m) for Mn(II) (5 μM) and a high K(m) for t-butyl hydroperoxide (100 mM). This activity, monitored by the formation of Mn(III)-malate or -malonate, is inhibited by Co(II) but not by superoxide dismutase. Optical evidence for binding of Mn(II) to the resting (ferric) enzyme is found in a change in intensity of the Soret peak upon titration with Mn(II). A potential role for Mn(III) in the antimycobacterial action of the antibiotic isoniazid is suggested by the rapid reduction of Mn(III)-malonate by this drug. The stoichiometry of the reaction is consistent with two single electron transfer steps per mole of isoniazid.