Evidence for heme oxygenase activity in a heme peroxidase.

Journal article

The heme peroxidase and heme oxygenase enzymes share a common heme prosthetic group but catalyze fundamentally different reactions, the first being H(2)O(2)-dependent oxidation of substrate using an oxidized Compound I intermediate, and the second O(2)-dependent degradation of heme. It has been proposed that these enzymes utilize a common reaction intermediate, a ferric hydroperoxide species, that sits at a crossroads in the mechanism and beyond which there are two mutually exclusive mechanistic pathways. Here, we present evidence to support this proposal in a heme peroxidase. Hence, we describe kinetic data for a variant of ascorbate peroxidase (W41A) which reacts slowly with tert-butyl hydroperoxide and does not form the usual peroxidase Compound I intermediate; instead, structural data show that a product is formed in which the heme has been cleaved at the alpha-meso position, analogous to the heme oxygenase mechanism. We interpret this to mean that the Compound I (peroxidase) pathway is shut down, so that instead the reaction intermediate diverts through the alternative (heme oxygenase) route. A mechanism for formation of the product is proposed and discussed in the light of what is known about the heme oxygenase reaction mechanism.

Authors: Badyal, S; Eaton, G; Mistry, S; Pipirou, Z; Basran, J

• Publication status: Published
• Journal: Biochemistry
• Volume: 48
• Issue: 22
• Pages: 4738-4746
• Publication date: 2009-06-01
• DOI: 10.1021/bi900118j
• EISSN: 1520-4995
• ISSN: 0006-2960
• Language: English
• Keywords: Aspartic Acid; Crystallization; Ascorbate Peroxidases; Tryptophan; Crystallography, X-Ray; Genetic Variation; tert-Butylhydroperoxide; Heme Oxygenase (Decyclizing); Peroxidases; Soybeans; Isoenzymes; Plant Proteins