5GLG

The novel function of Osm1 under anaerobic condition in the ER was revealed by crystal structure of Osm1, a soluble fumarate reductase in yeast

Summary for 5GLG

• Entry DOI: 10.2210/pdb5glg/pdb
• Descriptor: Fumarate reductase 2, SUCCINIC ACID, FLAVIN-ADENINE DINUCLEOTIDE, ... (4 entities in total)
• Functional Keywords: osm1, fumarate reductase, fad, oxidoreductase
• Biological source: Saccharomyces cerevisiae S288c (Baker's yeast)
• Total number of polymer chains: 1
• Total formula weight: 52499.31

Authors

Park, H.H.,Choi, J.Y. (deposition date: 2016-07-11, release date: 2017-07-12, Last modification date: 2024-03-20)

Primary citation

Kim, S.,Kim, C.M.,Son, Y.J.,Choi, J.Y.,Siegenthaler, R.K.,Lee, Y.,Jang, T.H.,Song, J.,Kang, H.,Kaiser, C.A.,Park, H.H.
Molecular basis of maintaining an oxidizing environment under anaerobiosis by soluble fumarate reductase.
Nat Commun, 9:4867-4867, 2018

PubMed 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.

PubMed: 30451826
DOI: 10.1038/s41467-018-07285-9

Experimental method

X-RAY DIFFRACTION (1.8 Å)