Cytochrome c peroxidase
Saccharomyces cerevisiae (Baker's yeast)
Many heme enzymes catalyze heterolysis of hydrogen peroxide (H2O2) and use H2O2 as an oxidant source for biological oxidative reactions. Cytochrome c peroxidase is such a enzyme, localized in the mitochondrial intermembrane space of aerobically grown yeast cells and protecting the organism against high concentrations of hydrogen peroxide. The catalytic mechanism couples the one-electron oxidation of ferrocytochrome c to the two-electron reduction of H2O2 to H2O. The enzyme reacts rapidly with H2O2, donating two reducing equivalents for the heterolytic oxygen-oxygen cleavage and generating its stable oxidized reaction intermediate, Compound I. Compound I is capable of oxidizing a wide variety of organic and inorganic compounds.
The structure here shows this peroxidase, composed of two domains, with the heme group buried within a crevice defined by these domains. Based upon this structure, a stereochemical mechanism for the formation of Compound I has been proposed. The mechanism involves base catalysis by the histidine defining the distal heme pocket within the crevice and stabilization of the transition state by the interacton of the positively charged arginine and histidine residues organizing the distal pocket with heme-bound peroxide. Cytochrome c peroxidase was the first heme enzyme whose structure had been determined by X-ray crystallography and as a result has contributed much to our understanding of the structural control of heme protein activity.
Protein Data Bank (PDB)
author: Aki Nagata