Catalase-peroxidase (KatG) Structure and Function

Catalase-peroxidases, or KatGs, are fascinating multifunctional enzymes the first of which, from Escherichia coli, was characterized in 1979. The first crystal structure of a KatG from Haloarcula morismortui was reported in 2002 as a homodimer in which the N- and C-terminal domains of each subunit are structurally very similar. The core structure and heme cavity of the N-terminal domain bear a strong resemblance to plant peroxidases, and the catalytic ability is provided by a crosslinked structure involving the side chains of a methionine, a tyrosine and a tryptophan in a reversible association with a mobile arginine. The indole N–H of the tryptophan of the Met-Tyr-Trp adduct is reversibly modified with a perhydroxy modification (Trp–OOH) formed in a rapid reaction with molecular oxygen or as an intermediate in the catalytic reaction cycle. KatGs also activate the anti-tubercular pro-drug isoniazid or isonicotinic acid hydrazide by converting it to isonicotinyl-NAD. Several isoniazid binding sites have been identified in different KatGs, all in locations where electron transfer can feed electrons to the heme for superoxide synthesis, required in the activation process, and the peroxidatic reaction.