The peroxidase–cyclooxygenase superfamily: Reconstructed evolution of critical enzymes of the innate immune system
Abstract
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. Proteins 2008. © 2008 Wiley‐Liss, Inc.
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“siRNA against NOX1 or NOXO1 decreased superoxide production and eNOS uncoupling in diabetic mice (1049).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [1049]
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- Authors
- Zamocky, M., Jakopitsch, C., Furtmüller, P. G., Dunand, C., & Obinger, C.
- Affiliations
- BOKU University (AT)
- University of Geneva (CH)
- Venue
- Proteins: Structure, Function, and Bioinformatics
- Publisher
- Wiley
- Published
- 2008-02-04
- Volume
- 72
- Issue
- 2
- Pages
- 589-605
- ISSN
- 0887-3585 (ISSN-L)
- 1097-0134
- OpenAlex
- W2153047806
- Cited by
- 170
- References
- 42
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 8 · 2023: 10 · 2022: 10 · 2021: 8 · 2020: 13 · 2019: 7 · 2018: 14 · 2017: 9 · 2016: 4 · 2015: 11 · 2014: 15 · 2013: 11 · 2012: 14
- FWCI
- 3.75
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Proteins Structure Function and Bioinformatics (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hemoglobin structure and function
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- heme peroxidase, myeloperoxidase, eosinophil peroxidase, lactoperoxidase, phylogenetic relationships, multigene family evolution, innate immunity, antimicrobial defense, structure-function relationship, gene family evolution
- MeSH terms
- Animals, Biological Evolution, Immunity, Innate, Peroxidases, Phylogeny, Prostaglandin-Endoperoxide Synthases, Likelihood Functions, Open Reading Frames, Sequence Alignment
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