Excessive hydrogen peroxide is harmful for almost all cell components, so its rapid and efficient removal is of essential importance for aerobically living organisms. Conversely, hydrogen peroxide acts as a second messenger in signal-transduction pathways. H 2 O 2 is degraded by peroxidases and catalases, the latter being able both to reduce H 2 O 2 to water and to oxidize it to molecular oxygen. Nature has evolved three protein families that are able to catalyze this dismutation at reasonable rates. Two of the protein families are heme enzymes: typical catalases and catalase-peroxidases. Typical catalases comprise the most abundant group found in Eubacteria, Archaeabacteria, Protista, Fungi, Plantae, and Animalia, whereas catalase-peroxidases are not found in plants and animals and exhibit both catalatic and peroxidatic activities. The third group is a minor bacterial protein family with a dimanganese active site called manganese catalases. Although catalyzing the same reaction (2 H 2 O 2 → 2 H 2 O + O 2 ), the three groups differ significantly in their overall and active-site architecture and the mechanism of reaction. Here, we present an overview of the distribution, phylogeny, structure, and function of these enzymes. Additionally, we report about their physiologic role, response to oxidative stress, and about diseases related to catalase deficiency in humans.

Cellobiose dehydrogenase, the only currently known extracellular flavocytochrome, is formed not only by a number of wood-degrading but also by various phytopathogenic fungi. This inducible enzyme participates in early events of lignocellulose degradation, as investigated in several basidiomycete fungi at the transcriptional and translational level. However, its role in the ascomycete fungi is not yet obvious. Comprehensive sequence analysis of CDH-encoding genes and their translational products reveals significant sequence similarities along the entire sequences and also a common domain architecture. All known cellobiose dehydrogenases fall into two related subgroups. Class-I members are represented by sequences from basidiomycetes whereas class-II comprises longer, more complex sequences from ascomycete fungi. Cellobiose dehydrogenase is typically a monomeric protein consisting of two domains joined by a protease-sensitive linker region. Each larger (dehydrogenase) domain is flavin-associated while the smaller (cytochrome) domains are haem-binding. The latter shorter domains are unique sequence motifs for all currently known flavocytochromes. Each cytochrome domain of CDH can bind a single haem b as prosthetic group. The larger dehydrogenase domain belongs to the glucose-methanol-choline (GMC) oxidoreductase superfamily - a widespread flavoprotein evolutionary line. The larger domains can be further divided into a flavin-binding subdomain and a substrate-binding subdomain. In addition, the class-II (but not class-I) proteins can possess a short cellulose-binding module of type 1 at their C-termini. All the cellobiose dehydrogenases oxidise cellobiose, cellodextrins, and lactose to the corresponding lactones using a wide spectrum of different electron acceptors. Their flexible specificity serves as a base for the development of possible biotechnological applications.

This review gives an overview about the structural organisation of different evolutionary lines of all enzymes capable of efficient dismutation of hydrogen peroxide. Major potential applications in biotechnology and clinical medicine justify further investigations. According to structural and functional similarities catalases can be divided in three subgroups. Typical catalases are homotetrameric haem proteins. The three-dimensional structure of six representatives has been resolved to atomic resolution. The central core of each subunit reveals a characteristic "catalase fold", extremely well conserved among this group. In the native tetramer structure pairs of subunits tightly interact via exchange of their N-terminal arms. This pseudo-knot structures implies a highly ordered assembly pathway. A minor subgroup ("large catalases") possesses an extra flavodoxin-like C-terminal domain. A > or = 25 A long channel leads from the enzyme surface to the deeply buried active site. It enables rapid and selective diffusion of the substrates to the active center. In several catalases NADPH is tightly bound close to the surface. This cofactor may prevent and reverse the formation of compound II, an inactive reaction intermediate. Bifunctional catalase-peroxidase are haem proteins which probably arose via gene duplication of an ancestral peroxidase gene. No detailed structural information is currently available. Even less is know about manganese catalases. Their di-manganese reaction centers may be evolutionary.

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The authors have reconstructed the phylogenetic relationships of the main evolutionary lines of mammalian heme containing peroxidases. The sequences of intensively investigated human myeloperoxidase, eosinophil peroxidase, and lactoperoxidase, which participate in host defence against infections, were aligned together with newly found open reading frames coding for highly similar putative peroxidase domains in all kingdoms of life. The evolutionary relationships were reconstructed using neighbor-joining, maximum parsimony, and maximum likelihood methods. It is demonstrated that this enzyme superfamily obeys the rules of birth-and-death model of multigene family evolution and contains proteins with a variety of function that could be grouped in seven subfamilies. On the basis of occurrence and the fact that two main enzymatic activities are related with these metalloproteins, they propose the name peroxidase-cyclooxygenase superfamily for this widely spread group of heme-containing oxidoreductases. Well known structure-function relationships in mammalian peroxidases formed the basis for the critical inspection of all subfamilies. The presented data unequivocally suggest that predecessor genes of mammalian heme peroxidases have segregated very early in evolution. Before organisms developed an acquired immunity, their antimicrobial defence depended on enzymes that were recruited upon pathogen invasion and could produce antimicrobial reaction products. Thus, these peroxidatic heme proteins evolved to important components in the innate immune defence system. This work shows that even in certain prokaryotic organisms, genes encoding putative antimicrobial enzymes are found providing a group of bacteria with an evolutionary advantage over the others.

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