Gene Symbol: frdA
Description: anaerobic fumarate reductase catalytic and NAD/flavoprotein subunit
Alias: ECK4150, JW4115
Species: Escherichia coli str. K-12 substr. MG1655

Top Publications

  1. Abo Amer A, Munn J, Jackson K, Aktas M, Golby P, Kelly D, et al. DNA interaction and phosphotransfer of the C4-dicarboxylate-responsive DcuS-DcuR two-component regulatory system from Escherichia coli. J Bacteriol. 2004;186:1879-89 pubmed
    ..DcuR specifically bound to the promoters of the three known DcuSR-regulated genes (dctA, dcuB, and frdA), with apparent K(D)s of 6 to 32 micro M for untreated DcuR and < or =1 to 2 microM for the acetylphosphate-..
  2. Cole S, Guest J. Genetic and physical characterization of lambda transducing phages (lambda frdA) containing the fumarate reductase gene of Escherichia coli K12. Mol Gen Genet. 1980;178:409-18 pubmed
    Two types of fumarate reductase transducing phages, lambda frdA, carrying the wild-type frdA gene but differing in the orientation of a R...
  3. Kenney W, Walker W, Singer T. Studies on succinate dehydrogenase. XX. Amino acid sequence around the flavin site. J Biol Chem. 1972;247:4510-3 pubmed
  4. Sucheta A, Cammack R, Weiner J, Armstrong F. Reversible electrochemistry of fumarate reductase immobilized on an electrode surface. Direct voltammetric observations of redox centers and their participation in rapid catalytic electron transport. Biochemistry. 1993;32:5455-65 pubmed
    ..This small boost to the catalytic current indicates that the low-potential [4Fe-4S] cluster can function as a second center for relaying electrons to the FAD. ..
  5. Luna Chavez C, Iverson T, Rees D, Cecchini G. Overexpression, purification, and crystallization of the membrane-bound fumarate reductase from Escherichia coli. Protein Expr Purif. 2000;19:188-96 pubmed
    ..6 A, b = 138.1 A, and c = 275.3 A. The purification and crystallization procedures are highly reproducible and the general procedure may prove useful for Complex IIs from other sources. ..
  6. Lohmeier E, Hagen D, Dickie P, Weiner J. Cloning and expression of fumarate reductase gene of Escherichia coli. Can J Biochem. 1981;59:158-64 pubmed
    ..Regulation of plasmid-encoded enzyme, like the chromosomally encoded enzyme, is dependent upon the presence of fumarate and anaerobiosis. ..
  7. Wood D, Darlison M, Wilde R, Guest J. Nucleotide sequence encoding the flavoprotein and hydrophobic subunits of the succinate dehydrogenase of Escherichia coli. Biochem J. 1984;222:519-34 pubmed
    ..a polypeptide of Mr 64268 that is strikingly homologous with the flavoprotein subunit of fumarate reductase (frdA gene product)...
  8. Weiner J, Cammack R, Cole S, Condon C, Honore N, Lemire B, et al. A mutant of Escherichia coli fumarate reductase decoupled from electron transport. Proc Natl Acad Sci U S A. 1986;83:2056-60 pubmed
    ..coli is a complex iron-sulfur flavoenzyme composed of four nonidentical subunits organized into two domains: FrdA and -B (a membrane-extrinsic catalytic domain) and FrdC and -D (a transmembrane anchor domain)...
  9. Jones H, Gunsalus R. Transcription of the Escherichia coli fumarate reductase genes (frdABCD) and their coordinate regulation by oxygen, nitrate, and fumarate. J Bacteriol. 1985;164:1100-9 pubmed
    ..culture, revealed that the frd mRNA transcript initiates with an adenine residue 93 bases prior to the start of frdA translation. No promoters internal to the frd genes were revealed with the plasmid promoter screening system...

More Information


  1. Niehaus F, Hantke K, Unden G. Iron content and FNR-dependent gene regulation in Escherichia coli. FEMS Microbiol Lett. 1991;68:319-23 pubmed
    ..Therefore FNR does not communicate with the iron pool regulating the Fur protein. ..
  2. Latour D, Weiner J. Assembly of Escherichia coli fumarate reductase holoenzyme. Biochem Cell Biol. 1989;67:251-9 pubmed
    ..FrdC and FrdD, the membrane anchor polypeptides, assembled rapidly into the membrane and then were capped with FrdA and FrdB in separate events...
  3. Maklashina E, Iverson T, Sher Y, Kotlyar V, Andréll J, Mirza O, et al. Fumarate reductase and succinate oxidase activity of Escherichia coli complex II homologs are perturbed differently by mutation of the flavin binding domain. J Biol Chem. 2006;281:11357-65 pubmed the conservation of amino acids near the dicarboxylate binding sites of the two enzymes is that there is a Glu (FrdA Glu-49) near the covalently bound FAD cofactor in most QFRs, which is replaced with a Gln (SdhA Gln-50) in SQRs...
  4. Iverson T, Luna Chavez C, Cecchini G, Rees D. Structure of the Escherichia coli fumarate reductase respiratory complex. Science. 1999;284:1961-6 pubmed
    ..Although fumarate reductase is not associated with any proton-pumping function, the two quinones are positioned on opposite sides of the membrane in an arrangement similar to that of the Q-cycle organization observed for cytochrome bc1...
  5. McNeil M, Hampton H, Hards K, Watson B, Cook G, Fineran P. The succinate dehydrogenase assembly factor, SdhE, is required for the flavinylation and activation of fumarate reductase in bacteria. FEBS Lett. 2014;588:414-21 pubmed publisher
    ..SdhE interacted with, and flavinylated, the flavoprotein subunit FrdA, whilst mutations in a conserved RGxxE motif impaired the complete flavinylation and activation of FRD...
  6. Cole S, Guest J. Amplification of fumarate reductase synthesis with lambdafrdA transducing phages and orientation of frdA gene expression. Mol Gen Genet. 1980;179:377-85 pubmed
  7. Cecchini G, Ackrell B, Deshler J, Gunsalus R. Reconstitution of quinone reduction and characterization of Escherichia coli fumarate reductase activity. J Biol Chem. 1986;261:1808-14 pubmed
  8. Seaver L, Imlay J. Are respiratory enzymes the primary sources of intracellular hydrogen peroxide?. J Biol Chem. 2004;279:48742-50 pubmed
    ..That source has not yet been identified. In respiring cells the rate of H2O2 production was approximately 0.5% the rate of total oxygen consumption, with only modest changes when cells used different carbon sources. ..
  9. Ackrell B, Cochran B, Cecchini G. Interactions of oxaloacetate with Escherichia coli fumarate reductase. Arch Biochem Biophys. 1989;268:26-34 pubmed
    ..The reason for the difference is not known. The redox potential of the FAD/FADH2 couple in FRD (Em approximately -55 mV) was also slightly more positive than that in cardiac succinate dehydrogenase (-90 mV). ..
  10. Utrilla J, Gosset G, Martinez A. ATP limitation in a pyruvate formate lyase mutant of Escherichia coli MG1655 increases glycolytic flux to D-lactate. J Ind Microbiol Biotechnol. 2009;36:1057-62 pubmed publisher
    ..strain of Escherichia coli MG1655 for D-lactate production was constructed by deleting the pflB, adhE and frdA genes; this strain was designated "CL3...
  11. Weiner J, Dickie P. Fumarate reductase of Escherichia coli. Elucidation of the covalent-flavin component. J Biol Chem. 1979;254:8590-3 pubmed
    ..Based on the spectral properties and pH-fluorescence dependence we have identified the linkage as 8 alpha-[N(3)-histidyl]FAD. ..
  12. Mewies M, McIntire W, Scrutton N. Covalent attachment of flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) to enzymes: the current state of affairs. Protein Sci. 1998;7:7-20 pubmed
    ..Case studies are presented for a variety of covalent flavoenzymes, from which general findings are beginning to emerge. ..
  13. Cole S, Grundstrom T, Jaurin B, Robinson J, Weiner J. Location and nucleotide sequence of frdB, the gene coding for the iron-sulphur protein subunit of the fumarate reductase of Escherichia coli. Eur J Biochem. 1982;126:211-6 pubmed
    ..The frdB gene is situated distal to and partially overlapped by frdA which codes for the flavoprotein subunit of the reductase...
  14. Cole S, Condon C, Lemire B, Weiner J. Molecular biology, biochemistry and bioenergetics of fumarate reductase, a complex membrane-bound iron-sulfur flavoenzyme of Escherichia coli. Biochim Biophys Acta. 1985;811:381-403 pubmed
  15. Fong S, Palsson B. Metabolic gene-deletion strains of Escherichia coli evolve to computationally predicted growth phenotypes. Nat Genet. 2004;36:1056-8 pubmed
    ..These results show that computational models can be used to predict the eventual effects of genetic modifications. ..
  16. Cohen Ben Lulu G, Francis N, Shimoni E, Noy D, Davidov Y, Prasad K, et al. The bacterial flagellar switch complex is getting more complex. EMBO J. 2008;27:1134-44 pubmed publisher
  17. Hirsch C, Rasminsky M, Davis B, Lin E. A FUMARATE REDUCTASE IN ESCHERICHIA COLI DISTINCT FROM SUCCINATE DEHYDROGENASE. J Biol Chem. 1963;238:3770-4 pubmed
  18. Messner K, Imlay J. Mechanism of superoxide and hydrogen peroxide formation by fumarate reductase, succinate dehydrogenase, and aspartate oxidase. J Biol Chem. 2002;277:42563-71 pubmed
    ..In contrast, succinate dehydrogenase, with high potential clusters, generates O2*- exclusively. The identities of enzyme autoxidation products are significant because O2*- and H2O2 damage cells in different ways. ..
  19. Leger C, Heffron K, Pershad H, Maklashina E, Luna Chavez C, Cecchini G, et al. Enzyme electrokinetics: energetics of succinate oxidation by fumarate reductase and succinate dehydrogenase. Biochemistry. 2001;40:11234-45 pubmed
    ..Importantly, comparisons are made with the electrocatalytic properties of SDH, the membrane-extrinsic catalytic domain of mitochondrial complex II. ..
  20. Dickie P, Weiner J. Purification and characterization of membrane-bound fumarate reductase from anaerobically grown Escherichia coli. Can J Biochem. 1979;57:813-21 pubmed
    ..This would indicate that the enzyme is a dimer. The purified enzyme has low, but measurable, succinate dehydrogenase activity. ..
  21. Ackrell B. Progress in understanding structure-function relationships in respiratory chain complex II. FEBS Lett. 2000;466:1-5 pubmed
    ..These offer new insights into structure-function relationships of this class of flavoenzymes, including evidence favoring protein movement during catalysis...
  22. Rothery R, Seime A, Spiers A, Maklashina E, Schröder I, Gunsalus R, et al. Defining the Q-site of Escherichia coli fumarate reductase by site-directed mutagenesis, fluorescence quench titrations and EPR spectroscopy. FEBS J. 2005;272:313-26 pubmed
    ..Overall, the data support a model for FrdABCD in which there is a single redox-active and dissociable Q-site. ..
  23. Schröder I, Gunsalus R, Ackrell B, Cochran B, Cecchini G. Identification of active site residues of Escherichia coli fumarate reductase by site-directed mutagenesis. J Biol Chem. 1991;266:13572-9 pubmed
    ..the role(s) of the conserved histidine 232, cysteine 247, and arginine 248 residues of the flavorprotein subunit (FrdA) in active site function...
  24. Tseng C, Hansen A, Cotter P, Gunsalus R. Effect of cell growth rate on expression of the anaerobic respiratory pathway operons frdABCD, dmsABC, and narGHJI of Escherichia coli. J Bacteriol. 1994;176:6599-605 pubmed each operon is regulated in response to changes in cell growth rate and in oxygen availability, expression of frdA-lacZ, dmsA-lacZ, and narG-lacZ fusion genes was examined during continuous culture...
  25. Blaut M, Whittaker K, Valdovinos A, Ackrell B, Gunsalus R, Cecchini G. Fumarate reductase mutants of Escherichia coli that lack covalently bound flavin. J Biol Chem. 1989;264:13599-604 pubmed
    ..The catalytic domain of fumarate reductase consists of the FrdA subunit, which contains the active site, and a FAD prosthetic group covalently attached to His44, plus the FrdB ..
  26. Yankovskaya V, Sablin S, Ramsay R, Singer T, Ackrell B, Cecchini G, et al. Inhibitor probes of the quinone binding sites of mammalian complex II and Escherichia coli fumarate reductase. J Biol Chem. 1996;271:21020-4 pubmed
    ..The results were analyzed in terms of the model of these dual sites of quinone binding in fumarate reductase, as well as the nature of the substituent in the 2-position of the dinitrophenol inhibitors. ..
  27. Cole S, Guest J. Production of a soluble form of fumarate reductase by multiple gene duplication in Escherichia coli K12. Eur J Biochem. 1979;102:65-71 pubmed
    ..2. The 33,000-Mr and 72,000-Mr components were identified as beta-lactamase and the amp-linked frdA gene product, fumarate reductase, respectively...
  28. Brandsch R, Bichler V. Covalent cofactor binding to flavoenzymes requires specific effectors. Eur J Biochem. 1989;182:125-8 pubmed
    ..Our results suggest that covalent modification and thus activation of these enzymes is dependent on specific metabolic intermediates which may act as allosteric effectors in the reaction. ..
  29. Huang C, Lin X, Wu L, Zhang D, Liu D, Wang S, et al. Systematic identification of the subproteome of Escherichia coli cell envelope reveals the interaction network of membrane proteins and membrane-associated peripheral proteins. J Proteome Res. 2006;5:3268-76 pubmed
    ..This established complete proteomic profile of E. coli envelope also sheds new insight into the function(s) of E. coli outer envelope. ..
  30. Grundstrom T, Jaurin B, Edlund T, Normark S. Physical mapping and expression of hybrid plasmids carrying chromosomal beta-lactamase genes of Escherichia coli K-12. J Bacteriol. 1980;143:1127-34 pubmed
    ..Two second-step regulatory mutations mapped within the same 370-base pair region as ampA1. This piece of deoxyribonucleic acid therefore contains ampA, a control sequence region for ampC. ..
  31. Lemire B, Robinson J, Weiner J. Identification of membrane anchor polypeptides of Escherichia coli fumarate reductase. J Bacteriol. 1982;152:1126-31 pubmed
    ..Unlike the well-characterized two-subunit form, the holoenzyme is not dependent on anions for activity and is not labile at alkaline pH. In these respects, it more closely resembles the membrane-bound activity. ..
  32. Cole S. Nucleotide sequence coding for the flavoprotein subunit of the fumarate reductase of Escherichia coli. Eur J Biochem. 1982;122:479-84 pubmed
    The nucleotide sequence of the frdA gene, which encodes the flavoprotein subunit of the fumarate reductase, of Escherichia coli, has been determined. A polypeptide of Mr = 66,052, containing 602 amino acid residues, is predicted...
  33. Iverson T, Luna Chavez C, Croal L, Cecchini G, Rees D. Crystallographic studies of the Escherichia coli quinol-fumarate reductase with inhibitors bound to the quinol-binding site. J Biol Chem. 2002;277:16124-30 pubmed publisher
    ..This acidic residue, Glu-C29, in the E. coli enzyme may act as a proton shuttle from the quinol during enzyme turnover...
  34. Cecchini G, Schröder I, Gunsalus R, Maklashina E. Succinate dehydrogenase and fumarate reductase from Escherichia coli. Biochim Biophys Acta. 2002;1553:140-57 pubmed
    ..The structure and function of SQR and QFR are briefly summarized in this communication and the similarities and differences in the membrane domain of the two enzymes are discussed. ..
  35. Grundstrom T, Jaurin B. Overlap between ampC and frd operons on the Escherichia coli chromosome. Proc Natl Acad Sci U S A. 1982;79:1111-5 pubmed
    ..C insertion in the promoter gave both increased transcription of ampC and a frameshift in this overlapping gene, resulting in readthrough proteins. Thus, we describe a type of very compact genetic organization of operons in prokaryotes. ..
  36. Hagerhall C. Succinate: quinone oxidoreductases. Variations on a conserved theme. Biochim Biophys Acta. 1997;1320:107-41 pubmed
  37. Mattevi A, Tedeschi G, Bacchella L, Coda A, Negri A, Ronchi S. Structure of L-aspartate oxidase: implications for the succinate dehydrogenase/fumarate reductase oxidoreductase family. Structure. 1999;7:745-56 pubmed
    ..Thus, LASPO, SDH and FRD form a class of functionally and structurally related oxidoreductases that are all able to reduce fumarate and to oxidise a dicarboxylate substrate. ..
  38. Trinh C, Carlson R, Wlaschin A, Srienc F. Design, construction and performance of the most efficient biomass producing E. coli bacterium. Metab Eng. 2006;8:628-38 pubmed
    ..The results show that the theoretical predictions are closely matched by the properties of the designed strain. ..
  39. Maklashina E, Hellwig P, Rothery R, Kotlyar V, Sher Y, Weiner J, et al. Differences in protonation of ubiquinone and menaquinone in fumarate reductase from Escherichia coli. J Biol Chem. 2006;281:26655-64 pubmed
    ..These findings represent an example of how enzymes that are designed to accommodate either UQ or MQ at a single Q binding site may nevertheless develop sufficient plasticity at the binding pocket to react differently with MQ and UQ. ..
  40. Maklashina E, Cecchini G. Comparison of catalytic activity and inhibitors of quinone reactions of succinate dehydrogenase (Succinate-ubiquinone oxidoreductase) and fumarate reductase (Menaquinol-fumarate oxidoreductase) from Escherichia coli. Arch Biochem Biophys. 1999;369:223-32 pubmed
    ..The pH activity profiles for E. coli QFR and SQR are similar showing maximal activity between pH 7.4 and 7.8, suggesting the importance of similar catalytic groups in quinol deprotonation and oxidation. ..
  41. Goh E, Bledsoe P, Chen L, Gyaneshwar P, Stewart V, Igo M. Hierarchical control of anaerobic gene expression in Escherichia coli K-12: the nitrate-responsive NarX-NarL regulatory system represses synthesis of the fumarate-responsive DcuS-DcuR regulatory system. J Bacteriol. 2005;187:4890-9 pubmed
    ..We measured beta-galactosidase expression from monocopy aspA-lacZ, frdA-lacZ, and dcuS-lacZ operon fusions in response to added nitrate and fumarate and with respect to the dcuR and narL ..
  42. Hudson J, Heffron K, Kotlyar V, Sher Y, Maklashina E, Cecchini G, et al. Electron transfer and catalytic control by the iron-sulfur clusters in a respiratory enzyme, E. coli fumarate reductase. J Am Chem Soc. 2005;127:6977-89 pubmed
  43. Johnson M, Kowal A, Morningstar J, Oliver M, Whittaker K, Gunsalus R, et al. Subunit location of the iron-sulfur clusters in fumarate reductase from Escherichia coli. J Biol Chem. 1988;263:14732-8 pubmed
    ..These new results are discussed in light of the amino acid sequences of the two subunits and the sequences of structurally well characterized iron-sulfur proteins containing [2Fe-2S], [3Fe-4S], and [4Fe-4S] centers. ..
  44. Condon C, Weiner J. Fumarate reductase of Escherichia coli: an investigation of function and assembly using in vivo complementation. Mol Microbiol. 1988;2:43-52 pubmed
    ..Thus separation of the DNA coding for the FRD C and FRD D proteins affected the ability of fumarate reductase to assemble into a functional complex. ..
  45. Imlay J. A metabolic enzyme that rapidly produces superoxide, fumarate reductase of Escherichia coli. J Biol Chem. 1995;270:19767-77 pubmed
    ..Since the turnover numbers for superoxide formation by other flavoenzymes are orders of magnitude lower than that of fumarate reductase (1600 min-1), additional steric or electronic factors must accelerate its autoxidation. ..
  46. Edlund T, Normark S. Recombination between short DNA homologies causes tandem duplication. Nature. 1981;292:269-71 pubmed
    ..We suggest that recombination between randomly occurring short homologies (12-13-bp long), could be a general mechanism to generate tandem duplications in the size range of 10 kilobases (kb). ..
  47. Iverson T, Luna Chavez C, Schröder I, Cecchini G, Rees D. Analyzing your complexes: structure of the quinol-fumarate reductase respiratory complex. Curr Opin Struct Biol. 2000;10:448-55 pubmed
    ..These structures revealed the cofactor organization linking the fumarate and quinol sites, and showed a cofactor arrangement across the membrane that is suggestive of a possible energy coupling function. ..
  48. Cecchini G, Sices H, Schröder I, Gunsalus R. Aerobic inactivation of fumarate reductase from Escherichia coli by mutation of the [3Fe-4S]-quinone binding domain. J Bacteriol. 1995;177:4587-92 pubmed
    ..These data suggest that the [3Fe-4S] cluster is intimately associated with one of the quinone binding sites found n fumarate reductase and succinate dehydrogenase. ..
  49. Westenberg D, Gunsalus R, Ackrell B, Sices H, Cecchini G. Escherichia coli fumarate reductase frdC and frdD mutants. Identification of amino acid residues involved in catalytic activity with quinones. J Biol Chem. 1993;268:815-22 pubmed
    ..The hydrophobic FrdC and FrdD subunits anchor the FrdA and FrdB catalytic subunits to the inner surface of the cytoplasmic membrane and are required for the enzyme to ..
  50. Tseng C, Albrecht J, Gunsalus R. Effect of microaerophilic cell growth conditions on expression of the aerobic (cyoABCDE and cydAB) and anaerobic (narGHJI, frdABCD, and dmsABC) respiratory pathway genes in Escherichia coli. J Bacteriol. 1996;178:1094-8 pubmed different levels of oxygen affect the expression of each operon, strains containing cyo-lacZ, cyd-lacZ, frdA-lacZ, dmsA-lacZ, and narG-lacZ fusions were grown in continuous culture at various degrees of air saturation...