Molecular basis of maintaining an oxidizing environment under anaerobiosis by soluble fumarate reductase
Name
s41467-018-07285-9.pdf
Description
Published version
Size
3.03 MB
Format
Adobe PDF
Checksum (MD5)
f2cfc03b122ecd470de585ac79f4dc61
Author(s)
Kim, Sunghwan
Kim, Chang Min
Son, Young-Jin
Choi, Jae Young
Siegenthaler, Rahel K.
Lee, Younho
Jang, Tae-Ho
Song, Jaeyoung
Kang, Hara
Kaiser, Chris A.
Date Issued
November 2018
Journal
Nature Communications
Publisher
Springer Science and Business Media LLC
Citation
Kim, Sunghwan et al. "Molecular basis of maintaining an oxidizing environment under anaerobiosis by soluble fumarate reductase." Nature Communications 9 (November 2018): 4867 © 2018, The Author(s).
Version
Final published version
Abstract
Osm1 and Frd1 are soluble fumarate reductases from yeast that are critical for allowing survival under anaerobic conditions. Although they maintain redox balance during anaerobiosis, the underlying mechanism is not understood. Here, we report the crystal structure of a eukaryotic soluble fumarate reductase, which is unique among soluble fumarate reductases as it lacks a heme domain. Structural and enzymatic analyses indicate that Osm1 has a specific binding pocket for flavin molecules, including FAD, FMN, and riboflavin, catalyzing their oxidation while reducing fumarate to succinate. Moreover, ER-resident Osm1 can transfer electrons from the Ero1 FAD cofactor to fumarate either by free FAD or by a direct interaction, allowing de novo disulfide bond formation in the absence of oxygen. We conclude that soluble eukaryotic fumarate reductases can maintain an oxidizing environment under anaerobic conditions, either by oxidizing cellular flavin cofactors or by a direct interaction with flavoenzymes such as Ero1. Keywords: Enzyme mechanisms; Oxidoreductases; X-ray crystallography
MIT Department
Massachusetts Institute of Technology. Department of Biology
Terms of Use
Creative Commons Attribution 4.0 International license
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DOI of Published Version
https://doi.org/10.1038/s41467-018-07285-9
