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discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
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for maintenance.
Metabolic Modeling Tutorial
discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
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discounted EARLY registration ends Dec 31, 2014
BioCyc websites down
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MetaCyc Protein: reduced flavorubredoxin

Gene: norV Accession Numbers: G7413 (MetaCyc), b2710, ECK2705

Synonyms: ygaJ, ygaI, ygaK, FlRd

Species: Escherichia coli K-12 substr. MG1655

Subunit composition of reduced flavorubredoxin = [NorV]4
         flavorubredoxin = NorV

Alternative forms of reduced flavorubredoxin: oxidized flavorubredoxin

Summary:
The NorV/NorW system constitutes a nitric oxide reductase that couples NADH oxidation to NO reduction [Gomes02, Vicente05]. The electron transfer chain begins with NADH oxidation by NorW, which then transfers the electron to the rubredoxin domain of NorV. Electrons travel through the protein to the catalytic di-iron site, where they are used for reduction of NO to N2O.

NorV (flavorubredoxin, FlRd) is a multidomain protein containing an amino-terminal β-lactamase-like module with a non-heme di-iron site as the catalytic center, a short chain flavodoxin-like module and a rubredoxin-like extension [Wasserfallen98, Gomes00, Gomes02]. A low-resolution structure was obtained by small-angle X-ray scattering, showing that the rubredoxin domain behaves as an independent domain [Petoukhov08].

The redox properties of NorV have been characterized [Vicente05], and the kinetics of electron transfer from NADH via NorW and NorV to NO has been measured [Vicente07]. The non-heme metal binding site of FlRd contains an atypical glutamate residue that is able to accomodate a zinc ion instead of iron [Schilling05].

Nitric oxide has been shown to have diverse biologial functions; however, the molecule also inactivates essential cellular enzymes. It is therefore essential that NO is removed from the cell. A kinetic model of the fate of NO within E. coli has been constructed and tested. Hmp appears to be the major NO sink both aerobically and under microaerophilic conditions, with an increasing role for the NorVW NO reductase system when Hmp becomes unavailable [Robinson13a].

Reports differ on whether [Gardner03] or not [daCosta03] exposure to physiological levels of NO under anaerobic conditions induces transcription of norVW [Gardner03] and on whether [Gardner02] or not [Vine11] mutation of norV eliminates inducible anarobic NO metabolism. FlRd levels are increased under nitrosative stress, but not under a combination of nitrosative and oxidative stress [Baptista12]. Mutation of norV does not affect survival of E. coli in mouse macrophages during early stages of infection, but does decrease survival at later stages [Baptista12]. In contrast, [Pullan07] reported no effect on survival. norV was reported to be important for survival and virulence of an EHEC strain [Shimizu12b].

Citations: [Gardner02a, Hutchings02, Flatley05, Poole05, Vicente08, De13]

Locations: cytosol

Map Position: [2,830,498 -> 2,831,937]

Molecular Weight of Polypeptide: 54.234 kD (from nucleotide sequence), 54.0 kD (experimental) [Wasserfallen98 ]

Molecular Weight of Multimer: 200.0 kD (experimental) [Wasserfallen98]

Unification Links: ASAP:ABE-0008910 , DIP:DIP-28070N , EchoBASE:EB2793 , EcoGene:EG12963 , EcoliWiki:b2710 , ModBase:Q46877 , OU-Microarray:b2710 , PortEco:norV , PR:PRO_000023399 , Pride:Q46877 , Protein Model Portal:Q46877 , RefSeq:NP_417190 , RegulonDB:G7413 , SMR:Q46877 , String:511145.b2710 , Swiss-Model:Q46877 , UniProt:Q46877

Relationship Links: InterPro:IN-FAMILY:IPR001279 , InterPro:IN-FAMILY:IPR004039 , InterPro:IN-FAMILY:IPR008254 , InterPro:IN-FAMILY:IPR016440 , InterPro:IN-FAMILY:IPR023957 , InterPro:IN-FAMILY:IPR024934 , InterPro:IN-FAMILY:IPR024935 , Pfam:IN-FAMILY:PF00258 , Pfam:IN-FAMILY:PF00301 , Pfam:IN-FAMILY:PF00753 , Prints:IN-FAMILY:PR00163 , Prosite:IN-FAMILY:PS50902 , Prosite:IN-FAMILY:PS50903 , Smart:IN-FAMILY:SM00849

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0046210 - nitric oxide catabolic process Inferred from experiment [Gardner02]
GO:0051289 - protein homotetramerization Inferred from experiment [Wasserfallen98]
GO:0071731 - response to nitric oxide Inferred from experiment [Gardner03]
GO:0055114 - oxidation-reduction process Inferred by computational analysis [UniProtGOA11a, GOA06]
Molecular Function: GO:0005506 - iron ion binding Inferred from experiment Inferred by computational analysis [GOA01a, Wasserfallen98]
GO:0009055 - electron carrier activity Inferred from experiment Inferred by computational analysis [GOA06, GOA01a, Vicente07]
GO:0010181 - FMN binding Inferred from experiment Inferred by computational analysis [GOA01a, Wasserfallen98]
GO:0016661 - oxidoreductase activity, acting on other nitrogenous compounds as donors Inferred from experiment [Gomes02]
GO:0042802 - identical protein binding Inferred from experiment [Wasserfallen98]
GO:0016491 - oxidoreductase activity Inferred by computational analysis [UniProtGOA11a, GOA06, GOA01a]
GO:0016966 - nitric oxide reductase activity Inferred by computational analysis [GOA01a]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11a, GOA01a]
Cellular Component: GO:0005737 - cytoplasm Inferred by computational analysis [UniProtGOA11, UniProtGOA11a, GOA06]
GO:0005829 - cytosol Inferred by computational analysis [DiazMejia09]

MultiFun Terms: metabolism energy production/transport electron carriers

Credits:
Imported from EcoCyc 27-May-2014 by Paley S , SRI International


Sequence Features

Feature Class Location Citations Comment
Protein-Segment 30 -> 210
[UniProt10]
UniProt: Zinc metallo-hydrolase; Sequence Annotation Type: region of interest;
Metal-Binding-Site 79
[UniProt10]
UniProt: Iron 1; Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 81
[UniProt10]
UniProt: Iron 1; Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 83
[UniProt10]
UniProt: Iron 2; Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 147
[UniProt10]
UniProt: Iron 1; Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 166
[UniProt10]
UniProt: Iron 1; Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 227
[UniProt10]
UniProt: Iron 2; Non-Experimental Qualifier: by similarity;
Conserved-Region 254 -> 393
[UniProt09]
UniProt: Flavodoxin-like;
Nucleotide-Phosphate-Binding-Region 260 -> 264
[UniProt10]
UniProt: FMN; Non-Experimental Qualifier: by similarity;
Nucleotide-Phosphate-Binding-Region 342 -> 369
[UniProt10]
UniProt: FMN; Non-Experimental Qualifier: by similarity;
Mutagenesis-Variant 413 -> 479
[UniProt10a]
Alternate sequence: missing; UniProt: Unable to accept electrons from nitric oxide reductase flrD-NAD(+) reductase (norW);
Conserved-Region 423 -> 474
[UniProt09]
UniProt: Rubredoxin-like;
Metal-Binding-Site 428
[UniProt10]
UniProt: Iron 3; Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 431
[UniProt10]
UniProt: Iron 3; Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 461
[UniProt10]
UniProt: Iron 3; Non-Experimental Qualifier: by similarity;
Metal-Binding-Site 464
[UniProt10]
UniProt: Iron 3; Non-Experimental Qualifier: by similarity;

History:
Markus Krummenacker on Tue Oct 14, 1997:
Gene object created from Blattner lab Genbank (v. M52) entry.


References

Baptista12: Baptista JM, Justino MC, Melo AM, Teixeira M, Saraiva LM (2012). "Oxidative stress modulates the nitric oxide defense promoted by Escherichia coli flavorubredoxin." J Bacteriol 194(14);3611-7. PMID: 22563051

daCosta03: da Costa PN, Teixeira M, Saraiva LM (2003). "Regulation of the flavorubredoxin nitric oxide reductase gene in Escherichia coli: nitrate repression, nitrite induction, and possible post-transcription control." FEMS Microbiol Lett 218(2);385-93. PMID: 12586421

De13: De Alba M, Bravo D, Medina M, Park SF, Mackey BM (2013). "Combined effect of sodium nitrite with high-pressure treatments on the inactivation of Escherichia coli BW25113 and Listeria monocytogenes NCTC 11994." Lett Appl Microbiol 56(2);155-60. PMID: 23206192

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Flatley05: Flatley J, Barrett J, Pullan ST, Hughes MN, Green J, Poole RK (2005). "Transcriptional responses of Escherichia coli to S-nitrosoglutathione under defined chemostat conditions reveal major changes in methionine biosynthesis." J Biol Chem 280(11);10065-72. PMID: 15647275

Gardner02: Gardner AM, Helmick RA, Gardner PR (2002). "Flavorubredoxin, an inducible catalyst for nitric oxide reduction and detoxification in Escherichia coli." J Biol Chem 277(10);8172-7. PMID: 11751865

Gardner02a: Gardner AM, Gardner PR (2002). "Flavohemoglobin detoxifies nitric oxide in aerobic, but not anaerobic, Escherichia coli. Evidence for a novel inducible anaerobic nitric oxide-scavenging activity." J Biol Chem 277(10);8166-71. PMID: 11751864

Gardner03: Gardner AM, Gessner CR, Gardner PR (2003). "Regulation of the nitric oxide reduction operon (norRVW) in Escherichia coli. Role of NorR and sigma54 in the nitric oxide stress response." J Biol Chem 278(12);10081-6. PMID: 12529359

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Gomes00: Gomes CM, Vicente JB, Wasserfallen A, Teixeira M (2000). "Spectroscopic studies and characterization of a novel electron-transfer chain from Escherichia coli involving a flavorubredoxin and its flavoprotein reductase partner." Biochemistry 39(51);16230-7. PMID: 11123953

Gomes02: Gomes CM, Giuffre A, Forte E, Vicente JB, Saraiva LM, Brunori M, Teixeira M (2002). "A novel type of nitric-oxide reductase. Escherichia coli flavorubredoxin." J Biol Chem 277(28);25273-6. PMID: 12101220

Hutchings02: Hutchings MI, Mandhana N, Spiro S (2002). "The NorR protein of Escherichia coli activates expression of the flavorubredoxin gene norV in response to reactive nitrogen species." J Bacteriol 184(16);4640-3. PMID: 12142437

Petoukhov08: Petoukhov MV, Vicente JB, Crowley PB, Carrondo MA, Teixeira M, Svergun DI (2008). "Quaternary structure of flavorubredoxin as revealed by synchrotron radiation small-angle X-ray scattering." Structure 16(9);1428-36. PMID: 18786405

Poole05: Poole RK (2005). "Nitric oxide and nitrosative stress tolerance in bacteria." Biochem Soc Trans 33(Pt 1);176-80. PMID: 15667299

Pullan07: Pullan ST, Gidley MD, Jones RA, Barrett J, Stevanin TM, Read RC, Green J, Poole RK (2007). "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 189(5);1845-55. PMID: 17189370

Robinson13a: Robinson JL, Brynildsen MP (2013). "A kinetic platform to determine the fate of nitric oxide in Escherichia coli." PLoS Comput Biol 9(5);e1003049. PMID: 23658508

Schilling05: Schilling O, Vogel A, Kostelecky B, Natal da Luz H, Spemann D, Spath B, Marchfelder A, Troger W, Meyer-Klaucke W (2005). "Zinc- and iron-dependent cytosolic metallo-beta-lactamase domain proteins exhibit similar zinc-binding affinities, independent of an atypical glutamate at the metal-binding site." Biochem J 385(Pt 1);145-53. PMID: 15324305

Shimizu12b: Shimizu T, Tsutsuki H, Matsumoto A, Nakaya H, Noda M (2012). "The nitric oxide reductase of enterohaemorrhagic Escherichia coli plays an important role for the survival within macrophages." Mol Microbiol 85(3);492-512. PMID: 22716767

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProt10: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Vicente05: Vicente JB, Teixeira M (2005). "Redox and spectroscopic properties of the Escherichia coli nitric oxide-detoxifying system involving flavorubredoxin and its NADH-oxidizing redox partner." J Biol Chem 280(41);34599-608. PMID: 16100392

Vicente07: Vicente JB, Scandurra FM, Rodrigues JV, Brunori M, Sarti P, Teixeira M, Giuffre A (2007). "Kinetics of electron transfer from NADH to the Escherichia coli nitric oxide reductase flavorubredoxin." FEBS J 274(3);677-86. PMID: 17181540

Vicente08: Vicente JB, Scandurra FM, Forte E, Brunori M, Sarti P, Teixeira M, Giuffre A (2008). "Kinetic characterization of the Escherichia coli nitric oxide reductase flavorubredoxin." Methods Enzymol 437;47-62. PMID: 18433622

Vine11: Vine CE, Cole JA (2011). "Nitrosative stress in Escherichia coli: reduction of nitric oxide." Biochem Soc Trans 39(1);213-5. PMID: 21265775

Wasserfallen98: Wasserfallen A, Ragettli S, Jouanneau Y, Leisinger T (1998). "A family of flavoproteins in the domains Archaea and Bacteria." Eur J Biochem 254(2);325-32. PMID: 9660187


Report Errors or Provide Feedback
Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 18.5 on Sat Dec 20, 2014, BIOCYC14B.