InterPro: IPR019793 Peroxidases heam-ligand binding site

Peroxidases are haem-containing enzymes that use hydrogen peroxide as the electron acceptor to catalyse a number of oxidative reactions. Most haem peroxidases follow the reaction scheme:

Fe³⁺ + H₂O₂ --> [Fe⁴⁺=O]R' (Compound I) + H₂O

[Fe⁴⁺=O]R' + substrate --> [Fe⁴⁺=O]R (Compound II) + oxidised substrate

[Fe⁴⁺=O]R + substrate --> Fe³⁺ + H₂O + oxidised substrate

In this mechanism, the enzyme reacts with one equivalent of H₂O₂ to give [Fe⁴⁺=O]R' (compound I). This is a two-electron oxidation/reduction reaction where H₂O₂ is reduced to water and the enzyme is oxidised. One oxidising equivalent resides on iron, giving the oxyferryl [1] intermediate, while in many peroxidases the porphyrin (R) is oxidised to the porphyrin pi-cation radical (R'). Compound I then oxidises an organic substrate to give a substrate radical [2].

Haem peroxidases include two superfamilies: one found in bacteria, fungi, plants and the second found in animals. The first one can be viewed as consisting of 3 major classes [3]. Class I, the intracellular peroxidases, includes: yeast cytochrome c peroxidase (CCP), a soluble protein found in the mitochondrial electron transport chain, where it probably protects against toxic peroxides; ascorbate peroxidase (AP), the main enzyme responsible for hydrogen peroxide removal in chloroplasts and cytosol of higher plants [4]; and bacterial catalase- peroxidases, exhibiting both peroxidase and catalase activities. It is thought that catalase-peroxidase provides protection to cells under oxidative stress [5].

Class II consists of secretory fungal peroxidases: ligninases, or lignin peroxidases (LiPs), and manganese-dependent peroxidases (MnPs). These are monomeric glycoproteins involved in the degradation of lignin. In MnP, Mn²⁺ serves as the reducing substrate [6]. Class II proteins contain four conserved disulphide bridges and two conserved calcium-binding sites.

Class III consists of the secretory plant peroxidases, which have multiple tissue-specific functions: e.g., removal of hydrogen peroxide from chloroplasts and cytosol; oxidation of toxic compounds; biosynthesis of the cell wall; defence responses towards wounding; indole-3-acetic acid (IAA) catabolism; ethylene biosynthesis; and so on [7]. Class III proteins are also monomeric glycoproteins, containing four conserved disulphide bridges and two calcium ions, although the placement of the disulphides differs from class II enzymes.

The crystal structures of a number of these proteins show that they share the same architecture - two all-alpha domains between which the haem group is embedded.

This entry represents the binding site for heam in a number of peroxidases.