Abbreviations:8fF (8-formyl flavin), 8AF (8-amino flavin), ASQ (anionic semiquinone), Bf (bifurcating), BTP (1,3-bis[tris(hydroxymethyl)amino]propane), CT (charge-transfer), ESI-MS (electrospray ionization mass spectrometry), ET (electron transfer), ETF (electron transferring flavoprotein), HQ (hydroquinone), LF (lumiflavin), OX/ASQ (oxidized/anionic semiquinone), TCEP (tris(2-carboxyethyl) phosphine)
Formation of 8fF confirmed, in air
8fF occurs in the ET site yet is responsive to the Bf site
- Burgess S.G.
- Messiha H.L.
- Katona G.
- Rigby S.E.J.
- Leys D.
- Scrutton N.S.
- Talfournier F.
- Munro A.W.
- Basran J.
- Sutcliffe M.J.
- Daff S.
- Chapman S.K.
- et al.
Influence of amino acid substitutions
- Talfournier F.
- Munro A.W.
- Basran J.
- Sutcliffe M.J.
- Daff S.
- Chapman S.K.
- et al.
A reductive reaction is confirmed in the absence of O2
Released flavins confirm a second product
Involvement of buffer in modification of flavin
Intermediacy of a radical and improved understanding of a long-wavelength band
Nature of the 726 nm species
Significance for published E°s
Production of modified flavin and possible significance of methide formation as a side-effect of ASQ stabilization
Contact between two flavins and implications for conformational change or protein associations
Flavin content of the RpaETF
Aerobic and anaerobic reactions
Samples were shielded from light and held at 4 °C for the duration of all reactions
Displacement of the ET flavin using ADP
Stability constant of ASQ
Structural model of RpaETF
Conflict of interest
Funding and additional information
- Supporting information
- On the mechanism of dehydrogenation of fatty acyl derivatives of coenzyme A. II. The electron transferring flavoprotein.J. Biol. Chem. 1956; 218: 717-731
- Unusual redox properties of electron-transfer flavoprotein from Methylophilus methylotrophus.Biochemistry. 1989; 28: 8582-8587
- The natural flavoprotein electron acceptor of trimethylaminne dehydrogenase.J. Biol. Chem. 1978; 253: 4086-4089
- The electron transfer flavoprotein: ubiquinone oxidoreductases.Biochim. Biophys. Acta. 2010; 1797: 1910-1916
- Electron-transferring flavoproteins.in: Müller F. Chemistry and Biochemistry of Flavoenzymes. CRC press, Boca Raton FL1991: 471-486
- Extensive domain motion and electron transfer in the human electron transferring flavoprotein·medium chain acyl-CoA dehydrogenase complex.J. Biol. Chem. 2004; 279: 32904-32912
- Three-dimensional structure of human electron transfer flavoprotein to 2.1-A resolution.Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 14355-14360
- Extensive conformational sampling in a ternary electron transfer complex.Nat. Struct. Biol. 2003; 10: 219-225
- Crystal structure of paracoccus denitrificans electron transfer flavoprotein: structural and electrostatic analysis of a conserved flavin binding domain.Biochemistry. 1999; 38: 1977-1989
- Electron-transferring flavoprotein has an AMP-binding site in addition to the FAD-binding site.J. Biochem. 1993; 114: 215-222
- Electron-transferring flavoproteins from pig and the methylotrophic bacterium W3A1 contains AMP as well as FAD.Biochem. Mol. Biol. Int. 1994; 32: 195-199
- Stabilization of non-productive conformations underpins rapid electron transfer to electron transferring flavoprotein.J. Biol. Chem. 2005; 280: 30361-30366
- The semiquinone swing in the bifurcating electron transferring flavoprotein/butyryl-coA dehydrogenase complex from Clostridium difficile.Nat. Commun. 2017; 8: 1577
- Dynamics driving function: new insights from electron transferring flavoproteins and partner complexes.FEBS J. 2007; 274: 5481-5504
- Purification of electron-transferring flavoprotein from Megasphaera elsdenii and binding of additional FAD with an unusual absorption spectrum.J. Biochem. 2003; 134: 719-729
- Purification and properties of electron-transferring flavoprotein from Peptostreptococcus elsdenii.J. Biol. Chem. 1974; 249: 2801-2810
- Interaction between NADH and electron-transferring flavoprotein from Megasphaera elsdenii.J. Biochem. 2013; 153: 565-572
- Reduction of ferredoxin or oxygen by flavin-based electron bifurcation in Megasphaera Elsdenii.FEBS J. 2015; 282: 3149-3160
- Studies on the mechanism of electron bifurcation catalyzed by electron transferring flavoprotein (Etf) and butyryl-CoA dehydrogenase (Bcd) of Acidaminococcus fermentans.J. Biol. Chem. 2014; 289: 5145-5157
- Molecular basis of the flavin-based electron-bifurcating caffeyl-CoA reductase reaction.FEBS Lett. 2018; 592: 332-342
- Structure-based electron-confurcation mechanism of the Ldh-EtfAB complex.eLife. 2022; 11e77095
- Cryoelectron microscopy structure and mechanism of the membrane-associated electron-bifurcating flavoprotein Fix/EtfABCX.Proc. Natl. Acad. Sci. U. S. A. 2021; 118e2016978118
- Spectroscopic, thermodynamic and computational evidence of the locations of the FADs in the nitrogen fixation-associated electron transfer flavoprotein.Chem. Sci. 2019; 10: 7762-7772
- Cloning and analysis of the genes for a novel electron-transferring flavoprotein from Megasphaera elsdenii.J. Biol. Chem. 1998; 273: 21015-21024
- Oxidation of the FAD cofactor to the 8-formyl-derivative in human electron-transferring flavoprotein.J. Biol. Chem. 2018; 293: 2829-2840
- A new form of mammalian electron transfer flavoprotein.Arch. Biochem. Biophys. 1992; 292: 594-599
- Energy conservation via electron-transferring flavoprotein in anaerobic bacteria.J. Bacteriol. 2008; 190: 784-791
- The effects of pH and semiquinone formation on the oxidation-reduction potentials of flavin mononucleotide: a reappraisal.Eur. J. Biochem. 1999; 265: 698-702
- Modulation of the redox properties of the flavin cofactor through hydrogen-bonding interactions with the N(5) atom: role of alpha Ser254 in the electron-transfer flavoprotein from the methylotrophic bacterium W3A1.Biochem. 2007; 46: 2289-2297
- alphaT244M mutation affects the redox, kinetic, and in vitro folding properties of Paracoccus denitrificans electron transfer flavoprotein.Biochemistry. 1997; 36: 4194-4202
- The catalytic mechanism of electron bifurcating electron transfer flavoproteins (ETFs) involves an intermediary complex with NAD+.J. Biol. Chem. 2019; 294: 3271-3283
- Essential genome of the metabolically versatile alphaproteobacterium Rhodopseudomonas Palustris.J. Bacteriol. 2015; 198: 867-876
- Defining electron bifurcation in the electron transferring flavoprotein family.J. Bacteriol. 2017; 199: e00440-17
- A reversible, charge-induced intramolecular C4a-S-cysteinyl-flavin in choline oxidase variant S101C.Biochemistry. 2017; 56: 6677-6690
- Spectroscopic evidence for direct flavin-flavin contact in a bifurcating electron transfer flavoprotein.J. Biol. Chem. 2020; 295: 12618-12634
- Involvement of a flavin iminoquinone methide in the formation of 6-hydroxyflavin mononucleotide in trimethylamine dehydrogenase: a rationale for the existence of 8R-methyl and C6-linked covalent flavoproteins.Biochem. 1997; 36: 7162-7168
- Flavin coenzymes: at the crossroads of biological redox Chemistry.Acc. Chem. Res. 1980; 13: 148-155
- Contrasting roles for two conserved arginines: stabilizing flavin semiquinone or quaternary structure, in bifurcating electron transfer flavoproteins.J. Biol. Chem. 2022; 298 (in press): 101733
- The functions of the flavin contact residuesαArg249 and βTyr16, in human electron transfer flavoprotein.Biochim. Biophys. Acta. 1999; 1433: 139-152
- Probing the dynamic interface between trimethylamine dehydrogenase (TMADH) and electron transferring flavoprotein (ETF) in the TMADH-2ETF complex: role of the Arg-α237 (ETF) and Tyr-442 (TMADH) residue pair.Biochemistry. 2008; 47: 5168-5181
- Alpha Arg-237 in Methylophilus methylotrophus (sp. W3A1) electron-transferring flavoprotein affords approximately 200-millivolt stabilization of the FAD anionic semiquinone and a kinetic block on full reduction to the dihydroquinone.J. Biol. Chem. 2001; 276: 20190-20196
- Flavin Modification and Redox Tuning in The Bifurcating Electron Transfer Flavoprotein From Rhodopseudomonas Palustris: Two Arginines With Different Roles.Ph. D., University of Kentucky, Lexington, KY2021
- Enzyme-mediated conversion of flavin adenine dinucleotide (FAD) to 8-formyl FAD in formate oxidase results in a modified cofactor with enhanced catalytic properties.Biochemistry. 2017; 56: 3800-3807
- Identification and properties of 8-hydroxyflavin-adenine dinucleotide in electron transfer flavoprotein from Peptostreptococcus elsdenii.Eur. J. Biochem. 1976; 63: 373-390
- A remarkable oxidative cascade that replaces the riboflavin C8 methyl with an amino group during roseoflavin biosynthesis.J. Am. Chem. Soc. 2016; 138: 8324-8327
- The microenvironment surrounding FAD mediates its ocnversion to 8-formyl-FAD in Aspergillus oryzae RIB40 formate oxidase.J. Biochem. 2019; 166: 67-75
- The crystal structure of RosB: insights into the reaction mechanism of the first member of a family of flavodoxin-like enzymes.Angew. Chem. Int. Ed. 2017; 56: 1146-1151
- Covalent flavinylation of vanillyl-alcohol oxidase is an autocatalytic process.FEBS J. 2008; 275: 5191-5200
- Roseoflavin as a blue light receptor analog: spectroscopic characterization.Photochem. Photobiol. 1980; 32: 393-398
- Studies on the active centers of flavoproteins: binding of 8-hydroxy-FAD and 8-hydroxy-FMN to apoproteins.in: Singer T.P. Flavins and Flavoproteins. Elsevier, Amsterdam1976: 334-340
- Identification and structure of a novel flavin prosthetic group associated with reduced nicotinamide adenine dinucleotide dehydrogenase from Peptostreptococcus elsdenii.J. Biol. Chem. 1973; 248: 6568-6570
- Properties of flavins where the 8-methyl group is replaced by mercapto- residues.J. Biol. Chem. 1979; 254: 8173-8178
- FAD roles in glucose catalytic oxidation studied by multiphase flow of extractive electrospray ionization (MF-EESI) mass spectrometry.Chem. Sci. 2018; 9: 594-599
- Potentiometric studies of native and flavin-substituted old yellow enzyme.J. Biol. Chem. 1985; 260: 13639-13647
- Absroption and emission spectroscopic characterization of 8-amino-riboflavin.Chem. Phys. 2009; 364: 19-30
- Flavodoxins and electron transferring flavoproteins.in: Boyer P. The Enzymes. Academic Press, NY1975: 57-118
- L-lactate oxidase and L-lactate monooxygenase: mechanistic variations on a common structural theme.Biochimie. 1995; 77: 631-642
- Photoirradiation generates an ultrastable 8-formyl FAD semiquinone radical with unusual properties in formate oxidase.Biochemistry. 2018; 57: 5818-5826
- A new flavin radical signal in the Na+-pumping NADH"quinone oxidoreductase from Vibrio cholerae.J. Biol. Chem. 2006; 281: 36482-36491
- Electron spin resonance studies on flavoenzymes.Biochem. Soc. Trans. 1985; 13: 593-600
- Identification of neutral and anioni 3α-substituted flavin semiquinones in flavoproteins by electron spin resonance spectroscopy.Arch. Biochem. Biophys. 1981; 208: 69-74
- The nature of compounds present in mixtures of oxidized and reduced flavin mononucleotides.Biochem. J. 1962; 85: 369-383
- Spectral characteristics of flavins at the semiquinoid oxidation level.J. Am. Chem. Soc. 1956; 78: 5323-5328
- Measurement of the electronic properties of the flavoprotein old yellow enzyme (OYE) and the OYE:p-Cl phenol charge-transfer complex using Stark spectroscopy.Biochem. 2003; 42: 991-999
- 8-mercaptoflavins as active-site probes of flavoenzymes.J. Biol. Chem. 1979; 254: 9640-9650
- Interaction of phenols with old yellow enzyme.J. Biol. Chem. 1976; 251: 5327-5336
- Distinct flavin properties underlie flavin-based electron bifurcation within a novel electron-transferring flavoprotein FixAB from Rhodopseudomonas palustris.J. Biol. Chem. 2018; 293: 4688-4701
- Identification and properties of new flavins in electron-transferring flavoprotein from Peptostreptococcus elsdenii and pig-liver glycolate oxidase.Eur. J. Biochem. 1974; 44: 579-591
- Structure-guided analyses of a key enzyme involved in the biosynthesis of an antivitamin.Biochemistry. 2018; 57: 5282-5288
- Interaction of two arginine residues in lactate oxidase with the ezyme flavin: conversion of FMN to 8-formyl-FMN.Proc. Natl. Acad. Sci. U. S. A. 2000; 97: 13039-13044
- What's in a covalent bond? On the role and formation of covalently bound flavin cofactors.FEBS J. 2009; 276: 3405-3427
- An experimental demonstration of the nuclear magnetic resonance assignments in the 6,7-dimethylisoalloxazine nucleus.J. Org. Chem. 1965; 30: 2056-2057
- Studien in der lumiflavin-reihe V. Spezifische reaktivität 8-ständiger substituenten am isoalloxazin-kern. Flavin-dimere.Helv. Chim. Acta. 1959; 27: 2164-2177
- Covalent attachment of flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) to enzymes: the current state of affairs.Prot. Sci. 1998; 7
- Autoflavination of apo6-hydroxy-D-nicotine oxidase.J. Biol. Chem. 1991; 266: 19056-19062
- Active site probes of flavoproteins.Biochem. Soc. Trans. 1980; 8: 246-257
- Crystal structure of D-amino acid oxidase: a case of active site mirror-image convergent evolution with flavocytochrome B2.Proc. Natl. Acad. Sci. U. S. A. 1996; 93: 7496-7501
- Molecular structure of flavocytochrome b2 at 2.4 A resolution.J. Mol. Biol. 1990; 212: 837-863
- Stabilization of lactate oxidase flavin anion radical by complex formation.J. Biol. Chem. 1980; 255: 8672-8677
- Pyruvate ferredoxin oxidoreductase and its radical intermediate.Chem. Rev. 2003; 103: 2333-2346
- Catalysis of oxidation of nitrogen compounds by flavin coenzymes in the presence of light.J. Biol. Chem. 1959; 234: 1297-1302
- Tuning the quantum chemical properties of flavins via modification at C8.J. Phys. Chem. B. 2021; 125: 12654-12669
- A continuous, spectrophotometric activity assay for nitrogenase using the reductant titanium(III) citrate.Anal. Biochem. 1994; 221: 379-386
- Electron donation to photosystem II in reaction center preparations.Biochim. Biophys. Acta. 1983; 723: 276-286
- Reduction midpoint potentials of bifurcating electron transfer flavoproteins.Met. Enzymol. 2019; 620: 365-398
- Electrophilicity of the 8 position of the isoalloxazine (flavine) ring system. Comment on the mechanism of oxidation of dihydroisoalloxazine.J. Am. Chem. Soc. 1974; 96: 3696-3697
- Tools for integrated sequence-structure analysis with UCSF Chimera.BMC Bioinformatics. 2006; 7: 339
- The crystal structure of L-lactate oxidase from Aerococcus viridans at 2.1 Å resolution reveals the mechanism of strict substrate recognition.Biochem. Biophys. Res. Commun. 2006; 350: 249-256
- Crystallographic studies of the Escherichia coli quinol-fumarate reductase with inhibitors bound to the quinol-binding site.J. Biol. Chem. 2002; 277: 16124-16130
- Formate oxidase, an enzyme of the glucose- methanol-choline oxidoreductase family, has a His-Arg pair and 8-formyl-FAD at the catalytic site.Biosci Biotechnol Biochem. 2011; 75: 1662-1667
- The SWISS-MODEL Workspace: A web-based environment for protein structure homology modelling.Bioinformatics. 2006; 22: 195-201
- SWISS-MODEL: homology modelling of protein structures and complexes.Nucleic Acids Res. 2014; 46: W296-W303
- UCSF Chimera - a visualization system for exploratory research and analysis.J. Comput. Chem. 2004; 25: 1605-1612
Present address for Nishya Mohamed-Raseek: Institute of Biological Chemistry, Washington State University, Pullman WA 99164.
User LicenseCreative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0) |
For non-commercial purposes:
- Read, print & download
- Redistribute or republish the final article
- Text & data mine
- Translate the article (private use only, not for distribution)
- Reuse portions or extracts from the article in other works
- Sell or re-use for commercial purposes
- Distribute translations or adaptations of the article
Elsevier's open access license policy