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Scavenging of superoxide by a membrane-bound superoxide oxidase
Stockholm Univ, Dept Biochem & Biophys, Stockholm, Sweden.
Stockholm Univ, Dept Biochem & Biophys, Stockholm, Sweden.
Univ Bern, Dept Chem & Biochem, Bern, Switzerland.ORCID iD: 0000-0001-6935-2475
Stockholm Univ, Dept Biochem & Biophys, Stockholm, Sweden.
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2018 (English)In: Nature Chemical Biology, ISSN 1552-4450, E-ISSN 1552-4469, Vol. 14, no 8, p. 788-793Article in journal (Refereed) Published
Abstract [en]

Superoxide is a reactive oxygen species produced during aerobic metabolism in mitochondria and prokaryotes. It causes damage to lipids, proteins and DNA and is implicated in cancer, cardiovascular disease, neurodegenerative disorders and aging. As protection, cells express soluble superoxide dismutases, disproportionating superoxide to oxygen and hydrogen peroxide. Here, we describe a membrane-bound enzyme that directly oxidizes superoxide and funnels the sequestered electrons to ubiquinone in a diffusion-limited reaction. Experiments in proteoliposomes and inverted membranes show that the protein is capable of efficiently quenching superoxide generated at the membrane in vitro. The 2.0 angstrom crystal structure shows an integral membrane di-heme cytochrome b poised for electron transfer from the P-side and proton uptake from the N-side. This suggests that the reaction is electrogenic and contributes to the membrane potential while also conserving energy by reducing the quinone pool. Based on this enzymatic activity, we propose that the enzyme family be denoted superoxide oxidase (SOO).

Place, publisher, year, edition, pages
NATURE PUBLISHING GROUP , 2018. Vol. 14, no 8, p. 788-793
National Category
Biochemistry and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-361498DOI: 10.1038/s41589-018-0072-xISI: 000438970200013PubMedID: 29915379OAI: oai:DiVA.org:uu-361498DiVA, id: diva2:1251199
Funder
Knut and Alice Wallenberg Foundation, 2012.0233Swedish Foundation for Strategic Research , FFL09-0008Swedish Research Council, 2017-04018Available from: 2018-09-26 Created: 2018-09-26 Last updated: 2018-09-26Bibliographically approved

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Carlsson, Jens

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