2wd4

Publication Abstract from PubMed

The heme peroxidases and heme oxygenase enzymes share a common heme prosthetic group but catalyse fundamentally different reactions, the first being H2O2-dependent oxidation of substrate using an oxidised Compound I intermediate, the second O2-dependent degradation of heme. It has been proposed that these enzymes utilise 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 t-butylhydroperoxide 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.

Evidence for Heme Oxygenase Activity in a Heme Peroxidase.,Raven E, Badyal S, Eaton G, Mistry S, Pipirou Z, Basran J, Metcalfe C, Gumiero A, Handa S, Moody P Biochemistry. 2009 Mar 23. PMID:19309109^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.