Gene Symbol: nrfA
Description: nitrite reductase, formate-dependent, cytochrome
Alias: ECK4063, JW4031
Species: Escherichia coli str. K-12 substr. MG1655

Top Publications

  1. Burlat B, Gwyer J, Poock S, Clarke T, Cole J, Hemmings A, et al. Cytochrome c nitrite reductase: from structural to physicochemical analysis. Biochem Soc Trans. 2005;33:137-40 pubmed
    The recent structural characterization of the NrfA from Escherichia coli provides a framework to rationalize the spectroscopic and functional properties of this enzyme...
  2. Page L, Griffiths L, Cole J. Different physiological roles of two independent pathways for nitrite reduction to ammonia by enteric bacteria. Arch Microbiol. 1990;154:349-54 pubmed
    ..Two short DNA sequences, 5'-TACCAT-3' and 5'-CTCCTT-3', were found in the promoters of operons known to be activated or repressed by the NarL protein.(ABSTRACT TRUNCATED AT 250 WORDS) ..
  3. Clarke T, Dennison V, Seward H, Burlat B, Cole J, Hemmings A, et al. Purification and spectropotentiometric characterization of Escherichia coli NrfB, a decaheme homodimer that transfers electrons to the decaheme periplasmic nitrite reductase complex. J Biol Chem. 2004;279:41333-9 pubmed
    Escherichia coli can reduce nitrite to ammonium via a 120-kDa decaheme homodimeric periplasmic nitrite reductase (NrfA) complex...
  4. Kemp G, Clarke T, Marritt S, Lockwood C, Poock S, Hemmings A, et al. Kinetic and thermodynamic resolution of the interactions between sulfite and the pentahaem cytochrome NrfA from Escherichia coli. Biochem J. 2010;431:73-80 pubmed publisher
    b>NrfA is a pentahaem cytochrome present in a wide-range of ?-, ?- and ?-proteobacteria...
  5. Clarke T, Cole J, Richardson D, Hemmings A. The crystal structure of the pentahaem c-type cytochrome NrfB and characterization of its solution-state interaction with the pentahaem nitrite reductase NrfA. Biochem J. 2007;406:19-30 pubmed
    ..nitrite reduction, the physiological role of NrfB is to mediate electron transfer to another pentahaem protein, NrfA, the enzyme that catalyses periplasmic nitrite or nitric oxide reduction...
  6. Pullan S, Gidley M, Jones R, Barrett J, Stevanin T, Read R, et al. Nitric oxide in chemostat-cultured Escherichia coli is sensed by Fnr and other global regulators: unaltered methionine biosynthesis indicates lack of S nitrosation. J Bacteriol. 2007;189:1845-55 pubmed NO led to up-regulation of multiple Fnr-repressed genes and down-regulation of Fnr-activated genes, including nrfA, which encodes cytochrome c nitrite reductase, providing strong evidence that there is NO inactivation of Fnr...
  7. Gwyer J, Richardson D, Butt J. Inhibiting Escherichia coli cytochrome c nitrite reductase: voltammetry reveals an enzyme equipped for action despite the chemical challenges it may face in vivo. Biochem Soc Trans. 2006;34:133-5 pubmed
    ..coli cytochrome c nitrite reductase is challenged by the presence of a number of small molecules. These results are discussed in light of the environment(s) that the enzyme may face before and after colonization of a human host. ..
  8. Allen J, Ferguson S. Variation of the axial haem ligands and haem-binding motif as a probe of the Escherichia coli c-type cytochrome maturation (Ccm) system. Biochem J. 2003;375:721-8 pubmed
    ..we report investigations of haem attachment to cytochromes altered to have the special Cys-Trp-Ser-Cys-Lys haem-binding motif, and Cys-Trp-Ser-Cys-His and Cys-Trp-Ala-Cys-His analogues, of the active-site haem of nitrite reductase NrfA.
  9. Browning D, Beatty C, Wolfe A, Cole J, Busby S. Independent regulation of the divergent Escherichia coli nrfA and acsP1 promoters by a nucleoprotein assembly at a shared regulatory region. Mol Microbiol. 2002;43:687-701 pubmed
    Expression from the Escherichia coli nrfA promoter (pnrfA) is activated by both the FNR protein (an anaerobically triggered transcription activator) and the NarL or NarP proteins (transcription activators triggered by nitrite and nitrate)...

More Information


  1. Kajie S, Anraku Y. Purification of a hexaheme cytochrome c552 from Escherichia coli K 12 and its properties as a nitrite reductase. Eur J Biochem. 1986;154:457-63 pubmed
    ..The apparent Michaelis constants for nitrite and hydroxylamine were 110 microM and 18 mM, respectively. The nitrite reductase activity of the cytochrome c552 was inhibited effectively by cupric ion and cyanide. ..
  2. Darwin A, Tormay P, Page L, Griffiths L, Cole J. Identification of the formate dehydrogenases and genetic determinants of formate-dependent nitrite reduction by Escherichia coli K12. J Gen Microbiol. 1993;139:1829-40 pubmed
  3. Gwyer J, Richardson D, Butt J. Resolving complexity in the interactions of redox enzymes and their inhibitors: contrasting mechanisms for the inhibition of a cytochrome c nitrite reductase revealed by protein film voltammetry. Biochemistry. 2004;43:15086-94 pubmed
  4. Fujita T. Studies on soluble cytochromes in Enterobacteriaceae. I. Detection, purification, and properties of cytochrome c-552 in anaerobically grown cells. J Biochem. 1966;60:204-15 pubmed
  5. Browning D, Lee D, Wolfe A, Cole J, Busby S. The Escherichia coli K-12 NarL and NarP proteins insulate the nrf promoter from the effects of integration host factor. J Bacteriol. 2006;188:7449-56 pubmed
    ..The acs-nrf regulatory region is conserved in other pathogenic E. coli strains and related enteric bacteria but differs in Salmonella enterica serovar Typhimurium. ..
  6. Gwyer J, Zhang J, Butt J, Ulstrup J. Voltammetry and in situ scanning tunneling microscopy of cytochrome C nitrite reductase on Au(111) electrodes. Biophys J. 2006;91:3897-906 pubmed
    Escherichia coli cytochrome c nitrite reductase (NrfA) catalyzes the six-electron reduction of nitrite to perform an important role in the biogeochemical cycling of nitrogen...
  7. Clarke T, Hemmings A, Burlat B, Butt J, Cole J, Richardson D. Comparison of the structural and kinetic properties of the cytochrome c nitrite reductases from Escherichia coli, Wolinella succinogenes, Sulfurospirillum deleyianum and Desulfovibrio desulfuricans. Biochem Soc Trans. 2006;34:143-5 pubmed
    ..interface and the active-site channel; these differences could be responsible for the observed variance in substrate activity and indicate that subtle changes in the NrfA structure may optimize the enzyme for different roles.
  8. Clarke T, Kemp G, van Wonderen J, Doyle R, Cole J, Tovell N, et al. Role of a conserved glutamine residue in tuning the catalytic activity of Escherichia coli cytochrome c nitrite reductase. Biochemistry. 2008;47:3789-99 pubmed publisher
    The pentaheme cytochrome c nitrite reductase (NrfA) of Escherichia coli is responsible for nitrite reduction during anaerobic respiration when nitrate is scarce...
  9. Darwin A, Hussain H, Griffiths L, Grove J, Sambongi Y, Busby S, et al. Regulation and sequence of the structural gene for cytochrome c552 from Escherichia coli: not a hexahaem but a 50 kDa tetrahaem nitrite reductase. Mol Microbiol. 1993;9:1255-65 pubmed
    The structural gene, nrfA, for cytochrome c552, which is the terminal reductase of the formate-dependent pathway for nitrite reduction to ammonia, has been located at co-ordinate 4366 on the physical map of the Escherichia coli chromosome...
  10. Iobbi Nivol C, Crooke H, Griffiths L, Grove J, Hussain H, Pommier J, et al. A reassessment of the range of c-type cytochromes synthesized by Escherichia coli K-12. FEMS Microbiol Lett. 1994;119:89-94 pubmed
    ..No other c-type cytochrome was detected under any growth condition tested. ..
  11. Hussain H, Grove J, Griffiths L, Busby S, Cole J. A seven-gene operon essential for formate-dependent nitrite reduction to ammonia by enteric bacteria. Mol Microbiol. 1994;12:153-63 pubmed
    The DNA sequence of the regulatory region and the structural gene, nrfA, for cytochrome c552 of Escherichia coli K-12 have been reported...
  12. Marritt S, Kemp G, Xiaoe L, Durrant J, Cheesman M, Butt J. Spectroelectrochemical characterization of a pentaheme cytochrome in solution and as electrocatalytically active films on nanocrystalline metal-oxide electrodes. J Am Chem Soc. 2008;130:8588-9 pubmed publisher
    The pentaheme containing cytochrome, NrfA, from Escherichia coli catalyzes the six-electron reduction of nitrite and the five-electron reduction of nitric oxide...
  13. Poock S, Leach E, Moir J, Cole J, Richardson D. Respiratory detoxification of nitric oxide by the cytochrome c nitrite reductase of Escherichia coli. J Biol Chem. 2002;277:23664-9 pubmed
    ..The periplasmic cytochrome c nitrite reductase (NrfA) of Escherichia coli catalyzes the respiratory reduction of nitrite, but in vitro studies have shown that it can ..
  14. Bamford V, Angove H, Seward H, Thomson A, Cole J, Butt J, et al. Structure and spectroscopy of the periplasmic cytochrome c nitrite reductase from Escherichia coli. Biochemistry. 2002;41:2921-31 pubmed
    The crystal structure and spectroscopic properties of the periplasmic penta-heme cytochrome c nitrite reductase (NrfA) of Escherichia coli are presented...
  15. Pope N, Cole J. Pyruvate and ethanol as electron donors for nitrite reduction by Escherichia coli K12. J Gen Microbiol. 1984;130:1279-84 pubmed
    ..We conclude that any third pathway for nitrite reduction contributes little to the in vivo rate of nitrite reduction by wild-type strains. ..
  16. Clarke T, Mills P, Poock S, Butt J, Cheesman M, Cole J, et al. Escherichia coli cytochrome c nitrite reductase NrfA. Methods Enzymol. 2008;437:63-77 pubmed publisher
    ..Nitric oxide (NO) is a proposed intermediate in this six-electron reduction and NrfA can use exogenous NO as a substrate...
  17. Browning D, Lee D, Spiro S, Busby S. Down-regulation of the Escherichia coli K-12 nrf promoter by binding of the NsrR nitric oxide-sensing transcription repressor to an upstream site. J Bacteriol. 2010;192:3824-8 pubmed publisher
    ..The NsrR target is inactivated by mutation at the Salmonella enterica serovar Typhimurium nrf promoter. ..
  18. van Wonderen J, Burlat B, Richardson D, Cheesman M, Butt J. The nitric oxide reductase activity of cytochrome c nitrite reductase from Escherichia coli. J Biol Chem. 2008;283:9587-94 pubmed publisher
    Cytochrome c nitrite reductase (NrfA) from Escherichia coli has a well established role in the respiratory reduction of nitrite to ammonium. More recently the observation that anaerobically grown E...
  19. Volkert M, Nguyen D, Beard K. Escherichia coli gene induction by alkylation treatment. Genetics. 1986;112:11-26 pubmed
    ..Moreover, since aidC is induced only by MNNG and aidI is induced only by MMS, these two genes are likely to be individually regulated. Thus, there appear to be at least three different regulatory mechanisms controlling aid genes. ..
  20. Filenko N, Spiro S, Browning D, Squire D, Overton T, Cole J, et al. The NsrR regulon of Escherichia coli K-12 includes genes encoding the hybrid cluster protein and the periplasmic, respiratory nitrite reductase. J Bacteriol. 2007;189:4410-7 pubmed
    ..include hcp-hcr (which were predicted in a recent bioinformatic study to be NsrR regulated) and the well-studied nrfA promoter that directs the expression of the periplasmic respiratory nitrite reductase...
  21. Adam E, Volkert M, Blot M. Cytochrome c biogenesis is involved in the transposon Tn5-mediated bleomycin resistance and the associated fitness effect in Escherichia coli. Mol Microbiol. 1998;28:15-24 pubmed
    ..Inactivation of potent DNA oxidants confers a better fitness to the bacterium carrying the transposon, suggesting a symbiotic relationship between host and transposon. ..
  22. Browning D, Grainger D, Beatty C, Wolfe A, Cole J, Busby S. Integration of three signals at the Escherichia coli nrf promoter: a role for Fis protein in catabolite repression. Mol Microbiol. 2005;57:496-510 pubmed
    ..Hence, Fis protein is a major factor responsible for catabolite repression at the nrf promoter, and Fis can override activation by FNR and NarL or NarP. ..
  23. Corker H, Poole R. Nitric oxide formation by Escherichia coli. Dependence on nitrite reductase, the NO-sensing regulator Fnr, and flavohemoglobin Hmp. J Biol Chem. 2003;278:31584-92 pubmed
    ..A cytochrome bd-deficient mutant retained NO-generating activity. The present study reveals a critical balance between NO-generating and -detoxifying activities during anaerobic growth. ..
  24. Wang H, Gunsalus R. The nrfA and nirB nitrite reductase operons in Escherichia coli are expressed differently in response to nitrate than to nitrite. J Bacteriol. 2000;182:5813-22 pubmed
    Escherichia coli possesses two distinct nitrite reductase enzymes encoded by the nrfA and nirB operons...
  25. Eaves D, Grove J, Staudenmann W, James P, Poole R, White S, et al. Involvement of products of the nrfEFG genes in the covalent attachment of haem c to a novel cysteine-lysine motif in the cytochrome c552 nitrite reductase from Escherichia coli. Mol Microbiol. 1998;28:205-16 pubmed four 'typical' haem-binding motifs, CXXCH-, characteristic of c-type cytochromes, the N-terminal region of NrfA includes a motif, CWSCK...