2WD4: Ascorbate Peroxidase As A Heme Oxygenase: W41a Variant Product With T-butyl Peroxide

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.
PDB ID: 2WD4Download
MMDB ID: 70647
PDB Deposition Date: 2009/3/19
Updated in MMDB: 2016/05
Experimental Method:
x-ray diffraction
Resolution: 1.4  Å
Source Organism:
Similar Structures:
Biological Unit for 2WD4: monomeric; determined by software (PISA)
Molecular Components in 2WD4
Label Count Molecule
Protein (1 molecule)
Ascorbate Peroxidase
Molecule annotation
Chemicals (5 molecules)
* Click molecule labels to explore molecular sequence information.

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