| Structural highlights
6c12 is a 4 chain structure with sequence from Ecoli. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , |
| Gene: | sdhA, b0723, JW0713 (ECOLI), sdhE, cptB, ygfY, b2897, JW2865 (ECOLI) |
| Activity: | Succinate dehydrogenase (quinone), with EC number 1.3.5.1 |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[SDHA_ECOLI] Two distinct, membrane-bound, FAD-containing enzymes are responsible for the catalysis of fumarate and succinate interconversion; the fumarate reductase is used in anaerobic growth, and the succinate dehydrogenase is used in aerobic growth.[1] [2] [3] [4] [SDHE_ECOLI] An FAD assembly protein, which accelerates covalent attachment of the cofactor into other proteins (PubMed:22474332, PubMed:26644464, PubMed:24374335). Plays an essential role in the assembly of succinate dehydrogenase (SDH, respiratory complex II), an enzyme complex that is a component of both the tricarboxylic acid cycle and the electron transport chain, and which couples the oxidation of succinate to fumarate with the reduction of ubiquinone (coenzyme Q) to ubiquinol. Required for flavinylation (covalent attachment of FAD) of the flavoprotein subunit SdhA of SDH (PubMed:24374335, PubMed:26644464, PubMed:22474332). Required for flavinylation of the flavoprotein subunit FdrA of fumarate reductase (FDR) (PubMed:26644464). Binds 2 different sites on the flavoprotein target FrdA (and presumably also SdhA), possibly positioning FAD and protein to facilitate the covalent bond formation; covalent attachment of FAD is not required for SDH or FDR complex enzyme formation (PubMed:26644464). Overexpression of this protein and YgfX (formerly cptA) restores production of prodigiosin antibiotic (Pig) in Serratia strains with deletions of sdhE-ygfX (PubMed:22474332).[5] [6] [7] [8]
Publication Abstract from PubMed
Succinate:quinone oxidoreductase (SQR) functions in energy metabolism, coupling the tricarboxylic acid cycle and electron transport chain in bacteria and mitochondria. The biogenesis of flavinylated SdhA, the catalytic subunit of SQR, is assisted by a highly conserved assembly factor termed SdhE in bacteria via an unknown mechanism. By using X-ray crystallography, we have solved the structure of Escherichia coli SdhE in complex with SdhA to 2.15-A resolution. Our structure shows that SdhE makes a direct interaction with the flavin adenine dinucleotide-linked residue His45 in SdhA and maintains the capping domain of SdhA in an "open" conformation. This displaces the catalytic residues of the succinate dehydrogenase active site by as much as 9.0 A compared with SdhA in the assembled SQR complex. These data suggest that bacterial SdhE proteins, and their mitochondrial homologs, are assembly chaperones that constrain the conformation of SdhA to facilitate efficient flavinylation while regulating succinate dehydrogenase activity for productive biogenesis of SQR.
Crystal structure of bacterial succinate:quinone oxidoreductase flavoprotein SdhA in complex with its assembly factor SdhE.,Maher MJ, Herath AS, Udagedara SR, Dougan DA, Truscott KN Proc Natl Acad Sci U S A. 2018 Mar 7. pii: 1800195115. doi:, 10.1073/pnas.1800195115. PMID:29514959[9]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ McNeil MB, Hampton HG, Hards KJ, Watson BN, Cook GM, Fineran PC. The succinate dehydrogenase assembly factor, SdhE, is required for the flavinylation and activation of fumarate reductase in bacteria. FEBS Lett. 2014 Jan 31;588(3):414-21. doi: 10.1016/j.febslet.2013.12.019. Epub, 2013 Dec 25. PMID:24374335 doi:http://dx.doi.org/10.1016/j.febslet.2013.12.019
- ↑ Yankovskaya V, Horsefield R, Tornroth S, Luna-Chavez C, Miyoshi H, Leger C, Byrne B, Cecchini G, Iwata S. Architecture of succinate dehydrogenase and reactive oxygen species generation. Science. 2003 Jan 31;299(5607):700-4. PMID:12560550 doi:10.1126/science.1079605
- ↑ Horsefield R, Yankovskaya V, Sexton G, Whittingham W, Shiomi K, Omura S, Byrne B, Cecchini G, Iwata S. Structural and computational analysis of the quinone-binding site of complex II (succinate-ubiquinone oxidoreductase): a mechanism of electron transfer and proton conduction during ubiquinone reduction. J Biol Chem. 2006 Mar 17;281(11):7309-16. Epub 2005 Dec 27. PMID:16407191 doi:http://dx.doi.org/10.1074/jbc.M508173200
- ↑ Ruprecht J, Yankovskaya V, Maklashina E, Iwata S, Cecchini G. Structure of Escherichia coli succinate:quinone oxidoreductase with an occupied and empty quinone-binding site. J Biol Chem. 2009 Oct 23;284(43):29836-46. Epub 2009 Aug 25. PMID:19710024 doi:10.1074/jbc.M109.010058
- ↑ McNeil MB, Iglesias-Cans MC, Clulow JS, Fineran PC. YgfX (CptA) is a multimeric membrane protein that interacts with the succinate dehydrogenase assembly factor SdhE (YgfY). Microbiology. 2013 Jul;159(Pt 7):1352-65. doi: 10.1099/mic.0.068510-0. Epub 2013 , May 8. PMID:23657679 doi:http://dx.doi.org/10.1099/mic.0.068510-0
- ↑ McNeil MB, Hampton HG, Hards KJ, Watson BN, Cook GM, Fineran PC. The succinate dehydrogenase assembly factor, SdhE, is required for the flavinylation and activation of fumarate reductase in bacteria. FEBS Lett. 2014 Jan 31;588(3):414-21. doi: 10.1016/j.febslet.2013.12.019. Epub, 2013 Dec 25. PMID:24374335 doi:http://dx.doi.org/10.1016/j.febslet.2013.12.019
- ↑ Maklashina E, Rajagukguk S, Starbird CA, McDonald WH, Koganitsky A, Eisenbach M, Iverson TM, Cecchini G. Binding of the Covalent Flavin Assembly Factor to the Flavoprotein Subunit of Complex II. J Biol Chem. 2016 Feb 5;291(6):2904-16. doi: 10.1074/jbc.M115.690396. Epub 2015, Dec 7. PMID:26644464 doi:http://dx.doi.org/10.1074/jbc.M115.690396
- ↑ McNeil MB, Clulow JS, Wilf NM, Salmond GP, Fineran PC. SdhE is a conserved protein required for flavinylation of succinate dehydrogenase in bacteria. J Biol Chem. 2012 May 25;287(22):18418-28. doi: 10.1074/jbc.M111.293803. Epub, 2012 Apr 3. PMID:22474332 doi:http://dx.doi.org/10.1074/jbc.M111.293803
- ↑ Maher MJ, Herath AS, Udagedara SR, Dougan DA, Truscott KN. Crystal structure of bacterial succinate:quinone oxidoreductase flavoprotein SdhA in complex with its assembly factor SdhE. Proc Natl Acad Sci U S A. 2018 Mar 7. pii: 1800195115. doi:, 10.1073/pnas.1800195115. PMID:29514959 doi:http://dx.doi.org/10.1073/pnas.1800195115
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