The role of Mn(II)-peroxidase activity of mycobacterial catalase-peroxidase in activation of the antibiotic isoniazid.
The catalase-peroxidase of Mycobacteria smegmatis exhibits Mn(II)-peroxidase activity characterized by a low Km for Mn(II) (5 microM) and a high Km 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.
Magliozzo
R S
RS
Departments of Physiology and Biophysics, Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461, USA.
Marcinkeviciene
J A
JA
D000995:Antitubercular Agents / Q000378:metabolism*; D001426:Bacterial Proteins; D007538:Isoniazid / Q000378:metabolism*; D007700:Kinetics; D008314:Malonates / Q000378:metabolism; D009161:Mycobacterium / Q000201:enzymology*; D010084:Oxidation-Reduction; D010544:Peroxidases / Q000378:metabolism*; D013054:Spectrophotometry, Atomic
D000995:Antitubercular Agents; D001426:Bacterial Proteins; D008314:Malonates; C030290:malonic acid; D010544:Peroxidases; C081610:catalase-peroxidase, bacteria; C051129:manganese peroxidase; D007538:Isoniazid