The HemQ coprohaem decarboxylase generates reactive oxygen species: implications for the evolution of classical haem biosynthesis
| Autor: | Charlie Hobbs, Mark Shepherd, Harry A. Dailey |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Coproporphyrins Staphylococcus aureus Free Radicals Haem peroxidase Protoporphyrins Oxidative phosphorylation Heme Biochemistry Superoxide dismutase 03 medical and health sciences chemistry.chemical_compound Bacterial Proteins polycyclic compounds Protoporphyrinogen Oxidase Molecular Biology Research Articles Horseradish Peroxidase chemistry.chemical_classification protoporphyrinogen Reactive oxygen species 030102 biochemistry & molecular biology biology Protoporphyrin IX Superoxide Superoxide Dismutase Coproporphyrinogen Oxidase Cell Biology Hydrogen Peroxide Catalase QR 030104 developmental biology coproporphyrinogen chemistry Models Chemical biology.protein Protoporphyrinogen oxidase Reactive Oxygen Species Research Article |
| Zdroj: | Biochemical Journal |
| ISSN: | 1470-8728 0264-6021 |
| Popis: | Bacteria require a haem biosynthetic pathway for the assembly of a variety of protein complexes, including cytochromes, peroxidases, globins, and catalase. Haem is synthesised via a series of tetrapyrrole intermediates, including non-metallated porphyrins, such as protoporphyrin IX, which is well known to generate reactive oxygen species in the presence of light and oxygen. Staphylococcus aureus has an ancient haem biosynthetic pathway that proceeds via the formation of coproporphyrin III, a less reactive porphyrin. Here, we demonstrate, for the first time, that HemY of S. aureus is able to generate both protoporphyrin IX and coproporphyrin III, and that the terminal enzyme of this pathway, HemQ, can stimulate the generation of protoporphyrin IX (but not coproporphyrin III). Assays with hydrogen peroxide, horseradish peroxidase, superoxide dismutase, and catalase confirm that this stimulatory effect is mediated by superoxide. Structural modelling reveals that HemQ enzymes do not possess the structural attributes that are common to peroxidases that form compound I [FeIV==O]+, which taken together with the superoxide data leaves Fenton chemistry as a likely route for the superoxide-mediated stimulation of protoporphyrinogen IX oxidase activity of HemY. This generation of toxic free radicals could explain why HemQ enzymes have not been identified in organisms that synthesise haem via the classical protoporphyrin IX pathway. This work has implications for the divergent evolution of haem biosynthesis in ancestral microorganisms, and provides new structural and mechanistic insights into a recently discovered oxidative decarboxylase reaction. |
| Databáze: | OpenAIRE |
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