A new framework for understanding substrate binding and functional diversity in haem peroxidases

The haem-containing peroxidase enzymes catalyse the H2O2-dependent oxidation of a wide variety of substrates and have provided a focal point for our more general understanding of structure/function relationships in other, more complex haem enzymes. Mechanistically, the haem peroxidases are well characterised: they share a common catalytic cycle that involves formation of a highoxidation-state (ferryl) intermediate. In contrast, our understanding of the structural features that control the diverse substrate specificity are less well defined. In this review, we discuss how recent spectroscopic and structural information for ascorbate peroxidase has provided new insight into the modus operandi of this enzyme and how this has helped to clarify certain aspects of the catalytic and, in particular, the substrate binding properties of the closely related cytochrome c peroxidase enzyme, which has been a benchmark for peroxidase catalysis over more than 20 years.