Structural highlights
Function
OSM1_YEAST Irreversibly catalyzes the reduction of fumarate to succinate. Together with the second isozyme of soluble fumarate reductase (FRD1), essential for anaerobic growth. Involved in maintaining redox balance during oxygen deficiency conditions. Reduction of fumarate is the main source of succinate during fermentation, and under anaerobic conditions, the formation of succinate is strictly required for the reoxidation of FADH(2).[1] [2] [3] [4]
Publication Abstract from PubMed
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.
Molecular basis of maintaining an oxidizing environment under anaerobiosis by soluble fumarate reductase.,Kim S, Kim CM, Son YJ, Choi JY, Siegenthaler RK, Lee Y, Jang TH, Song J, Kang H, Kaiser CA, Park HH Nat Commun. 2018 Nov 19;9(1):4867. doi: 10.1038/s41467-018-07285-9. PMID:30451826[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Camarasa C, Grivet JP, Dequin S. Investigation by 13C-NMR and tricarboxylic acid (TCA) deletion mutant analysis of pathways for succinate formation in Saccharomyces cerevisiae during anaerobic fermentation. Microbiology. 2003 Sep;149(Pt 9):2669-78. PMID:12949191 doi:http://dx.doi.org/10.1099/mic.0.26007-0
- ↑ Camarasa C, Faucet V, Dequin S. Role in anaerobiosis of the isoenzymes for Saccharomyces cerevisiae fumarate reductase encoded by OSM1 and FRDS1. Yeast. 2007 May;24(5):391-401. PMID:17345583 doi:http://dx.doi.org/10.1002/yea.1467
- ↑ Muratsubaki H, Enomoto K. One of the fumarate reductase isoenzymes from Saccharomyces cerevisiae is encoded by the OSM1 gene. Arch Biochem Biophys. 1998 Apr 15;352(2):175-81. PMID:9587404 doi:http://dx.doi.org/10.1006/abbi.1998.0583
- ↑ Arikawa Y, Enomoto K, Muratsubaki H, Okazaki M. Soluble fumarate reductase isoenzymes from Saccharomyces cerevisiae are required for anaerobic growth. FEMS Microbiol Lett. 1998 Aug 1;165(1):111-6. PMID:9711846
- ↑ Kim S, Kim CM, Son YJ, Choi JY, Siegenthaler RK, Lee Y, Jang TH, Song J, Kang H, Kaiser CA, Park HH. Molecular basis of maintaining an oxidizing environment under anaerobiosis by soluble fumarate reductase. Nat Commun. 2018 Nov 19;9(1):4867. doi: 10.1038/s41467-018-07285-9. PMID:30451826 doi:http://dx.doi.org/10.1038/s41467-018-07285-9
