nitrite reductases


Summary: A group of enzymes that oxidize diverse nitrogenous substances to yield nitrite. (Enzyme Nomenclature, 1992) EC 1.

Top Publications

  1. Beaumont H, Lens S, Reijnders W, Westerhoff H, van Spanning R. Expression of nitrite reductase in Nitrosomonas europaea involves NsrR, a novel nitrite-sensitive transcription repressor. Mol Microbiol. 2004;54:148-58 pubmed
    ..The findings are consistent with the hypothesis that N. europaea expresses NirK as a defence against the toxic NO(2) (-) that is produced during nitrification...
  2. Schmidt I, van Spanning R, Jetten M. Denitrification and ammonia oxidation by Nitrosomonas europaea wild-type, and NirK- and NorB-deficient mutants. Microbiology. 2004;150:4107-14 pubmed
    ..In contrast, the mutant strains remained inactive. For recovery of ammonia oxidation activity the NO concentration had to be adjusted to about 10 p.p.m. in the aeration gas...
  3. Kujime M, Izumi C, Tomura M, Hada M, Fujii H. Effect of a tridentate ligand on the structure, electronic structure, and reactivity of the copper(I) nitrite complex: role of the conserved three-histidine ligand environment of the type-2 copper site in copper-containing nitrite reductases. J Am Chem Soc. 2008;130:6088-98 pubmed publisher
    It is postulated that the copper(I) nitrite complex is a key reaction intermediate of copper containing nitrite reductases (Cu-NiRs), which catalyze the reduction of nitrite to nitric oxide (NO) gas in bacterial denitrification...
  4. Antonyuk S, Strange R, Sawers G, Eady R, Hasnain S. Atomic resolution structures of resting-state, substrate- and product-complexed Cu-nitrite reductase provide insight into catalytic mechanism. Proc Natl Acad Sci U S A. 2005;102:12041-6 pubmed
    Copper-containing nitrite reductases catalyze the reduction of nitrite to nitric oxide (NO), a key step in denitrification that results in the loss of terrestrial nitrogen to the atmosphere...
  5. Nojiri M, Xie Y, Inoue T, Yamamoto T, Matsumura H, Kataoka K, et al. Structure and function of a hexameric copper-containing nitrite reductase. Proc Natl Acad Sci U S A. 2007;104:4315-20 pubmed
    ..The discussion of the intermolecular electron transfer process from cytochrome c(550) to the H. denitrificans NIR is based on x-ray crystallographic and kinetic results...
  6. Tota B, Quintieri A, Angelone T. The emerging role of nitrite as an endogenous modulator and therapeutic agent of cardiovascular function. Curr Med Chem. 2010;17:1915-25 pubmed
  7. Nojiri M, Koteishi H, Nakagami T, Kobayashi K, Inoue T, Yamaguchi K, et al. Structural basis of inter-protein electron transfer for nitrite reduction in denitrification. Nature. 2009;462:117-20 pubmed publisher
  8. Dalsgaard T, Simonsen U, Fago A. Nitrite-dependent vasodilation is facilitated by hypoxia and is independent of known NO-generating nitrite reductase activities. Am J Physiol Heart Circ Physiol. 2007;292:H3072-8 pubmed
    ..Possible reaction mechanisms for nitrite vasoactivity, including formation of S-nitrosothiols within the arterial smooth muscle, are discussed. ..
  9. Wijma H, Jeuken L, Verbeet M, Armstrong F, Canters G. Protein film voltammetry of copper-containing nitrite reductase reveals reversible inactivation. J Am Chem Soc. 2007;129:8557-65 pubmed
    ..Binding of nitrite to the type-2 site does not affect the midpoint potential of the type-1 site, thereby excluding cooperativity between the two sites. ..

More Information


  1. Levy Booth D, Winder R. Quantification of nitrogen reductase and nitrite reductase genes in soil of thinned and clear-cut Douglas-fir stands by using real-time PCR. Appl Environ Microbiol. 2010;76:7116-25 pubmed publisher
    ..Overall, no clear influence of tree thinning on nifH, nirS, and nirK was observed. However, soil OM, C, and N were found to significantly influence N-cycling gene abundance. ..
  2. 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. ..
  3. Kartal B, Kuypers M, Lavik G, Schalk J, Op den Camp H, Jetten M, et al. Anammox bacteria disguised as denitrifiers: nitrate reduction to dinitrogen gas via nitrite and ammonium. Environ Microbiol. 2007;9:635-42 pubmed
    ..This indicates that anammox bacteria could be mediating dissimilatory nitrate reduction to ammonium in natural ecosystems. ..
  4. Ellis M, Grossmann J, Eady R, Hasnain S. Genomic analysis reveals widespread occurrence of new classes of copper nitrite reductases. J Biol Inorg Chem. 2007;12:1119-27 pubmed
  5. Hough M, Eady R, Hasnain S. Identification of the proton channel to the active site type 2 Cu center of nitrite reductase: structural and enzymatic properties of the His254Phe and Asn90Ser mutants. Biochemistry. 2008;47:13547-53 pubmed publisher
    ..Two distinct proton channels have previously been identified in copper nitrite reductases based on high- to atomic-resolution crystal structures...
  6. Stirpe A, Guzzi R, Wijma H, Verbeet M, Canters G, Sportelli L. Calorimetric and spectroscopic investigations of the thermal denaturation of wild type nitrite reductase. Biochim Biophys Acta. 2005;1752:47-55 pubmed
    ..Moreover, it is found that the conformational changes within the type-1 copper environments precede the denaturation of the whole protein. No evidence of protein dissociation within the temperature range investigated was observed. ..
  7. Pittman M, Kelly D. Electron transport through nitrate and nitrite reductases in Campylobacter jejuni. Biochem Soc Trans. 2005;33:190-2 pubmed
    ..The pathways of electron transport to nitrate and nitrite are reviewed in this paper. Nitrate is considered as a potential in vivo electron acceptor and a role for nitrite reductase in NO detoxification is suggested. ..
  8. Cantera J, Stein L. Molecular diversity of nitrite reductase genes (nirK) in nitrifying bacteria. Environ Microbiol. 2007;9:765-76 pubmed
    ..Deduced NirK protein sequences were highly similar to other copper-containing nitrite reductases including conserved motifs...
  9. Kataoka K, Yamaguchi K, Kobayashi M, Mori T, Bokui N, Suzuki S. Structure-based engineering of Alcaligenes xylosoxidans copper-containing nitrite reductase enhances intermolecular electron transfer reaction with pseudoazurin. J Biol Chem. 2004;279:53374-8 pubmed
    ..from Achromobacter cycloclastes pseudoazurin (AcPAZ) to wild-type and mutant Alcaligenes xylosoxidans nitrite reductases (AxNIRs) was investigated using steady-state kinetics and electrochemical methods...
  10. Heylen K, Gevers D, Vanparys B, Wittebolle L, Geets J, Boon N, et al. The incidence of nirS and nirK and their genetic heterogeneity in cultivated denitrifiers. Environ Microbiol. 2006;8:2012-21 pubmed
    Gene sequence analysis of nirS and nirK, both encoding nitrite reductases, was performed on cultivated denitrifiers to assess their incidence in different bacterial taxa and their taxonomical value...
  11. Stöhr C, Stremlau S. Formation and possible roles of nitric oxide in plant roots. J Exp Bot. 2006;57:463-70 pubmed
  12. Kandeler E, Deiglmayr K, Tscherko D, Bru D, Philippot L. Abundance of narG, nirS, nirK, and nosZ genes of denitrifying bacteria during primary successions of a glacier foreland. Appl Environ Microbiol. 2006;72:5957-62 pubmed
    ..This study yields an initial insight into the ecology of bacteria carrying genes for the denitrification pathway in a newly developing alpine environment. ..
  13. Lund M, Smith J, Francis C. Diversity, abundance and expression of nitrite reductase (nirK)-like genes in marine thaumarchaea. ISME J. 2012;6:1966-77 pubmed publisher
    ..Like the ammonia-oxidizing bacteria, AOA encode a gene homologous to copper-containing nitrite reductases (nirK), which has been studied very little to date...
  14. Bartossek R, Nicol G, Lanzen A, Klenk H, Schleper C. Homologues of nitrite reductases in ammonia-oxidizing archaea: diversity and genomic context. Environ Microbiol. 2010;12:1075-88 pubmed publisher
    ..Here we report on the occurrence of genes encoding potential homologues of copper-dependent nitrite reductases (NirK) in ammonia-oxidizing archaea of soils and other environments using metagenomic approaches and PCR ..
  15. Merkle A, Lehnert N. Binding and activation of nitrite and nitric oxide by copper nitrite reductase and corresponding model complexes. Dalton Trans. 2012;41:3355-68 pubmed publisher
    The reduction of nitrite to nitric oxide in dissimilatory denitrification is carried out by copper nitrite reductases (CuNIRs) via a type 2 copper site...
  16. Crawford J, Isbell T, Huang Z, Shiva S, Chacko B, Schechter A, et al. Hypoxia, red blood cells, and nitrite regulate NO-dependent hypoxic vasodilation. Blood. 2006;107:566-74 pubmed
    ..These data support a function for RBC hemoglobin as an allosterically and redox-regulated nitrite reductase whose "enzyme activity" couples hypoxia to increased NO-dependent blood flow. ..
  17. Basu S, Grubina R, Huang J, Conradie J, Huang Z, Jeffers A, et al. Catalytic generation of N2O3 by the concerted nitrite reductase and anhydrase activity of hemoglobin. Nat Chem Biol. 2007;3:785-94 pubmed
  18. Pinho D, Besson S, Brondino C, de Castro B, Moura I. Copper-containing nitrite reductase from Pseudomonas chlororaphis DSM 50135. Eur J Biochem. 2004;271:2361-9 pubmed
    ..Electrochemical experiments show that azurin from the same organism can donate electrons to this enzyme. ..
  19. Muro Pastor M, Strauss J, Ramon A, Scazzocchio C. A paradoxical mutant GATA factor. Eukaryot Cell. 2004;3:393-405 pubmed
    ..The in vivo methylation pattern of the promoter is drastically altered, suggesting the recruitment of one or more unknown transcription factors and/or a local distortion on the DNA double helix. ..
  20. Maia L, Moura J. Nitrite reduction by xanthine oxidase family enzymes: a new class of nitrite reductases. J Biol Inorg Chem. 2011;16:443-60 pubmed publisher
    ..Our results define a new catalytic performance for AOR-the nitrite reduction-and propose a new class of molybdenum-containing nitrite reductases.
  21. Tocheva E, Eltis L, Murphy M. Conserved active site residues limit inhibition of a copper-containing nitrite reductase by small molecules. Biochemistry. 2008;47:4452-60 pubmed publisher
    ..Overall, the data substantiate the roles of Asp98 and Ile257 in discriminating substrate from other small anions. ..
  22. Sato K, Dennison C. Active site comparison of CoII blue and green nitrite reductases. Chemistry. 2006;12:6647-59 pubmed
    Copper-containing nitrite reductases (NiRs) possess type 1 (T1) and type 2 (T2) copper sites and can be either green or blue in color owing to differences at their T1 centers...
  23. Yamaguchi K, Kataoka K, Kobayashi M, Itoh K, Fukui A, Suzuki S. Characterization of two type 1 Cu sites of Hyphomicrobium denitrificans nitrite reductase: a new class of copper-containing nitrite reductases. Biochemistry. 2004;43:14180-8 pubmed
    ..and the 35-kDa C-terminal domain having type 1 Cu-binding and type 2 Cu-binding motifs such as common nitrite reductases (NIRs)...
  24. Cosby K, Partovi K, Crawford J, Patel R, Reiter C, Martyr S, et al. Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation. Nat Med. 2003;9:1498-505 pubmed
    ..These results suggest that nitrite represents a major bioavailable pool of NO, and describe a new physiological function for hemoglobin as a nitrite reductase, potentially contributing to hypoxic vasodilation. ..
  25. Shiva S, Rassaf T, Patel R, Gladwin M. The detection of the nitrite reductase and NO-generating properties of haemoglobin by mitochondrial inhibition. Cardiovasc Res. 2011;89:566-73 pubmed publisher
    ..These data reveal redox and allosteric mechanisms that control Hb-mediated nitrite reduction and regulation of mitochondrial function, and support a role for Hb-catalysed nitrite reduction in hypoxic vasodilation. ..
  26. Quan D, Min D, Cha G, Nam H. Electrochemical characterization of biosensor based on nitrite reductase and methyl viologen co-immobilized glassy carbon electrode. Bioelectrochemistry. 2006;69:267-75 pubmed
    ..In addition to the full characterization of the biosensor, kinetic study was also conducted in solution and the homogeneous rate constant (k(2)) between NiR and MV were determined by chronoamperometry to be 5.8 x 10(5) M(-1) s(-1). ..
  27. Basu S, Azarova N, Font M, King S, Hogg N, Gladwin M, et al. Nitrite reductase activity of cytochrome c. J Biol Chem. 2008;283:32590-7 pubmed publisher
    ..These data suggest an additional role for cytochrome c as a nitrite reductase that may play an important role in regulating mitochondrial function and contributing to hypoxic, redox, and apoptotic signaling within the cell. ..
  28. Brenner S, Heyes D, Hay S, Hough M, Eady R, Hasnain S, et al. Demonstration of proton-coupled electron transfer in the copper-containing nitrite reductases. J Biol Chem. 2009;284:25973-83 pubmed publisher
    ..61 +/- 0.02 between 3 and 10 mM. Our work provides the first experimental demonstration of proton-coupled electron transfer in both the resting and substrate-bound AxNiR, and two protons were found to be involved in turnover. ..
  29. Astier Y, Canters G, Davis J, Hill H, Verbeet M, Wijma H. Sensing nitrite through a pseudoazurin-nitrite reductase electron transfer relay. Chemphyschem. 2005;6:1114-20 pubmed
  30. Rinaldo S, Sam K, Castiglione N, Stelitano V, Arcovito A, Brunori M, et al. Observation of fast release of NO from ferrous d? haem allows formulation of a unified reaction mechanism for cytochrome cd? nitrite reductases. Biochem J. 2011;435:217-25 pubmed publisher
    ..We present a reaction mechanism proposed to be applicable to all cytochromes cd1 and conclude that the d1 haem has evolved to have low affinity for NO, as compared with other ferrous haems...
  31. Han C, Wright G, Fisher K, Rigby S, Eady R, Hasnain S. Characterization of a novel copper-haem c dissimilatory nitrite reductase from Ralstonia pickettii. Biochem J. 2012;444:219-26 pubmed publisher
    NiRs (nitrite reductases) convert nitrite into NO in the denitrification process. RpNiR (Ralstonia pickettii NiR), a new type of dissimilatory Cu-containing NiR with a C-terminal haem c domain from R...
  32. Gladwin M, Kim Shapiro D. The functional nitrite reductase activity of the heme-globins. Blood. 2008;112:2636-47 pubmed publisher
    ..We will review these reactions in the biologic framework of hypoxic signaling in blood and the heart. ..
  33. Van Alst N, Wellington M, Clark V, Haidaris C, Iglewski B. Nitrite reductase NirS is required for type III secretion system expression and virulence in the human monocyte cell line THP-1 by Pseudomonas aeruginosa. Infect Immun. 2009;77:4446-54 pubmed publisher
    ..These data suggest that NO generated via nitrite reductase NirS contributes to the regulation of expression of selected virulence factors in P. aeruginosa PA14. ..
  34. Caddick M, Jones M, van Tonder J, Le Cordier H, Narendja F, Strauss J, et al. Opposing signals differentially regulate transcript stability in Aspergillus nidulans. Mol Microbiol. 2006;62:509-19 pubmed
    ..Regulated transcript stability is therefore an integral part of the adaptive response. This represents the first example of distinct physiological signals competing to differentially regulate transcripts at the level of deadenylation. ..
  35. Almeida M, Silveira C, Moura J. Biosensing nitrite using the system nitrite redutase/Nafion/methyl viologen--a voltammetric study. Biosens Bioelectron. 2007;22:2485-92 pubmed
    ..The operational stability of the biosensor and the influence of some possible interferences were evaluated. ..
  36. Ellis M, Dodd F, Sawers G, Eady R, Hasnain S. Atomic resolution structures of native copper nitrite reductase from Alcaligenes xylosoxidans and the active site mutant Asp92Glu. J Mol Biol. 2003;328:429-38 pubmed
    ..04, 1.15 and 1.12A resolutions, respectively. These structures provide the basis from which to build a detailed mechanism of this important enzyme...
  37. Shiva S, Huang Z, Grubina R, Sun J, Ringwood L, MacArthur P, et al. Deoxymyoglobin is a nitrite reductase that generates nitric oxide and regulates mitochondrial respiration. Circ Res. 2007;100:654-61 pubmed
  38. Kim S, Fushinobu S, Zhou S, Wakagi T, Shoun H. Eukaryotic nirK genes encoding copper-containing nitrite reductase: originating from the protomitochondrion?. Appl Environ Microbiol. 2009;75:2652-8 pubmed publisher
    ..These results show that the fungal denitrifying system has the same origin as its bacterial counterpart. ..
  39. Tocheva E, Rosell F, Mauk A, Murphy M. Side-on copper-nitrosyl coordination by nitrite reductase. Science. 2004;304:867-70 pubmed publisher
    ..The side-on copper-nitrosyl in nitrite reductase expands the possibilities for nitric oxide interactions in copper proteins such as superoxide dismutase and prions...
  40. Chen Z, Luo X, Hu R, Wu M, Wu J, Wei W. Impact of long-term fertilization on the composition of denitrifier communities based on nitrite reductase analyses in a paddy soil. Microb Ecol. 2010;60:850-61 pubmed publisher
    ..Therefore, long-term fertilization resulted in a strong impact on the community structure of nirK populations only, and total organic carbon was the dominant factor in relation to the variations of nir community sizes. ..
  41. Lücker S, Wagner M, Maixner F, Pelletier E, Koch H, Vacherie B, et al. A Nitrospira metagenome illuminates the physiology and evolution of globally important nitrite-oxidizing bacteria. Proc Natl Acad Sci U S A. 2010;107:13479-84 pubmed publisher
  42. Grubina R, Huang Z, Shiva S, Joshi M, Azarov I, Basu S, et al. Concerted nitric oxide formation and release from the simultaneous reactions of nitrite with deoxy- and oxyhemoglobin. J Biol Chem. 2007;282:12916-27 pubmed
  43. Nohl H, Staniek K, Kozlov A. The existence and significance of a mitochondrial nitrite reductase. Redox Rep. 2005;10:281-6 pubmed
    ..In this paper, we describe the identity and the function of mitochondrial nitrite reductase and the consequences of NO-recycling in the metabolic compartment of mitochondria. ..
  44. Murphy M, Turley S, Adman E. Structure of nitrite bound to copper-containing nitrite reductase from Alcaligenes faecalis. Mechanistic implications. J Biol Chem. 1997;272:28455-60 pubmed
  45. 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
    ..In contrast, the nirB nitrite reductase is optimally synthesized only when nitrate or nitrite is in excess of the cell's capacity to consume it. Revised regulatory schemes are presented for NarL and NarP in control of the two operons. ..
  46. Suzuki S, Kataoka K, Yamaguchi K. Metal coordination and mechanism of multicopper nitrite reductase. Acc Chem Res. 2000;33:728-35 pubmed
    ..The noncoordinated Asp and His residues around type 2 Cu play important roles in both the electron-transfer and the catalytic processes. ..
  47. Ichiki H, Tanaka Y, Mochizuki K, Yoshimatsu K, Sakurai T, Fujiwara T. Purification, characterization, and genetic analysis of Cu-containing dissimilatory nitrite reductase from a denitrifying halophilic archaeon, Haloarcula marismortui. J Bacteriol. 2001;183:4149-56 pubmed publisher
  48. Zhao Y, Lukoyanov D, Toropov Y, Wu K, Shapleigh J, Scholes C. Catalytic function and local proton structure at the type 2 copper of nitrite reductase: the correlation of enzymatic pH dependence, conserved residues, and proton hyperfine structure. Biochemistry. 2002;41:7464-74 pubmed
    ..Mutation of Ile289 to Ala and Val caused minor perturbation to enzyme activity, but as detected by ENDOR, allowed formate binding. Thus, bulky Ile289 may exclude non-nitrite ligands from the Type 2 active site. ..
  49. Muro Pastor M, Gonzalez R, Strauss J, Narendja F, Scazzocchio C. The GATA factor AreA is essential for chromatin remodelling in a eukaryotic bidirectional promoter. EMBO J. 1999;18:1584-97 pubmed
    ..The results presented cast doubts on the role of NirA as the unique transducer of the nitrate induction signal. We demonstrate, for the first time in vivo, that a GATA factor is involved directly in chromatin remodelling. ..
  50. Braker G, Fesefeldt A, Witzel K. Development of PCR primer systems for amplification of nitrite reductase genes (nirK and nirS) to detect denitrifying bacteria in environmental samples. Appl Environ Microbiol. 1998;64:3769-75 pubmed
    ..This was shown by applying one generally amplifying primer combination for each nir gene developed in this study to total DNA preparations from aquatic habitats...
  51. Sasaki S, Karube I, Hirota N, Arikawa Y, Nishiyama M, Kukimoto M, et al. Application of nitrite reductase from Alcaligenes faecalis S-6 for nitrite measurement. Biosens Bioelectron. 1998;13:1-5 pubmed
    ..Measurements using a batch-flow type system gave a lower detection limit of 0.01 mg/l. This is sufficient for the detection of nitrite in natural waters...
  52. Hawker K, Montague P, Kinghorn J. Nitrate reductase and nitrite reductase transcript levels in various mutants of Aspergillus nidulans: confirmation of autogenous regulation. Mol Gen Genet. 1992;231:485-8 pubmed
  53. Stohr C, Strube F, Marx G, Ullrich W, Rockel P. A plasma membrane-bound enzyme of tobacco roots catalyses the formation of nitric oxide from nitrite. Planta. 2001;212:835-41 pubmed
    ..The PM-associated NI-NOR may reduce the apoplastic nitrite produced by PM-NR in vivo and may play a role in nitrate signalling via NO formation. ..