doi:10.1038/nindia.2009.252 Published online 23 July 2009
The mammalian lactoperoxidase enzyme is responsible for converting an anti-tuberculosis prodrug (an inactive substance) into and active drug, new research has found1.
The enzyme converts frontline antituberculosis prodrug isoniazid (INH) into an active drug against Mycobacterium tuberculosis in a manner similar to that of catalase peroxidase (MtCP), which is found in the tuberculosis causing bug.
Heme containing peroxidases are a large group of enzymes that act as catalysts in the oxidation of halides, pseudohalides and organic aromatic molecules with the help of hydrogen peroxide. They generate products with a wide range of antimicrobial activities including the conversion of INH to its active species.
Mammalian lactoperoxidase (LPO) consists of a most efficient substrate binding site on the rear side of the heme molecule. This site is connected to the protein surface through a long hydrophobic channel highly compatible to aromatic ligands.
Earlier studies have shown the interaction of these aromatic compounds –salicylhydroxamic acid (SHA), benzylhydroxamic acid (BHA) and acetyl salicylic acid (ASA) – with LPO. The studies showed that SHA and BHA act as inhibitors while ASA is oxidized into a free radical of ASA.
The researchers further extended these studies to include INH and obtain these results.
"This suggests another important application of LPO in the control of Mycobacterium tuberculosis infection," says lead researcher Tej Pal Singh from the Department of Biophysics, All India Institute of Medical Sciences, New Delhi.