Iron Uptake Oxidoreductase (IruO) Uses a Flavin Adenine Dinucleotide Semiquinone Intermediate for Iron-Siderophore Reduction
| Autor: | Marek J. Kobylarz, Graham A. Heieis, Michael E. P. Murphy, Slade A. Loutet |
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| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Models Molecular Siderophore Iron Siderophores Reductase Crystallography X-Ray Biochemistry 03 medical and health sciences chemistry.chemical_compound Oxidoreductase Benzoquinones Enzyme kinetics Anaerobiosis Cloning Molecular Heme Ferrichrome chemistry.chemical_classification Flavin adenine dinucleotide Binding Sites 030102 biochemistry & molecular biology General Medicine Kinetics 030104 developmental biology chemistry Flavin-Adenine Dinucleotide Molecular Medicine Oxidoreductases Oxidation-Reduction Nicotinamide adenine dinucleotide phosphate NADP |
| Zdroj: | ACS chemical biology. 12(7) |
| ISSN: | 1554-8937 |
| Popis: | Many pathogenic bacteria including Staphylococcus aureus use iron-chelating siderophores to acquire iron. Iron uptake oxidoreductase (IruO), a flavin adenine dinucleotide (FAD)-containing nicotinamide adenine dinucleotide phosphate (NADPH)-dependent reductase from S. aureus, functions as a reductase for IsdG and IsdI, two paralogous heme degrading enzymes. Also, the gene encoding for IruO was shown to be required for growth of S. aureus on hydroxamate siderophores as a sole iron source. Here, we show that IruO binds the hydroxamate-type siderophores desferrioxamine B and ferrichrome A with low micromolar affinity and in the presence of NADPH, Fe(II) was released. Steady-state kinetics of Fe(II) release provides kcat/Km values in the range of 600 to 7000 M–1 s–1 for these siderophores supporting a role for IruO as a siderophore reductase in iron utilization. Crystal structures of IruO were solved in two distinct conformational states mediated by the formation of an intramolecular disulfide bond. A putative... |
| Databáze: | OpenAIRE |
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