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MetaCyc Enzyme: NADH:ubiquinone oxidoreductase II

Gene: ndh Accession Numbers: EG10649 (MetaCyc), b1109, ECK1095

Synonyms: NDH-2, NADH dhII, NADH dehydrogenase II, NQR, NADH-quinone reductase

Species: Escherichia coli K-12 substr. MG1655

Summary:
NADH:ubiquinone oxidoreductase II (NDH-2) is a type IIA NADH dehydrogenase that catalyzes the transfer of electrons from NADH to the quinone pool in the cytoplasmic membrane. NDH-2 is one of two distinct NADH dehydrogenases in E. coli. In contrast to NDH-1 (encoded by the nuo genes), NDH-2 utilizes NADH exclusively, and electron flow from NADH to ubiquinone does not generate an electrochemical gradient [Matsushita87, Hayashi89, Calhoun93].

During glucose limited aerobic growth E. coli directs electron flux through both NADH dehydrogenases [Calhoun93a]. Electron transport from NADH to oxygen is not affected in a strain lacking NDH-I but is significantly reduced in a strain lacking NDH-II; similarly nitrate respiration with NADH was only slightly affected in a strain lacking NDH-I but significantly reduced in a strain lacking NDH-II. This suggests that NDH-II is used preferentially in aerobic and nitrate respiration [Tran97].

NDH-2 is a strongly membrane-associated protein; it contains an FAD cofactor and copurifies with phospholipids [Young78, Jaworowski81, Campbell83]. Phosphatidylethanolamine appears to be required for full enzymatic activity in vivo [Mileykovskaya93]. The enzyme contains a thiolate-bound Cu(I) ion, and a putative copper binding site has been identified [Rapisarda02]. Heterooligomers of NDH-1 and NDH-2 have been identified by electrophoresis and sucrose gradient centrifugation is suggestive of a supramolecular organisation in the membrane [Sousa11].

NDH-2 can generate superoxide radicals and hydrogen peroxide by autooxidation of the FAD cofactor [Messner99] when the enzyme is overproduced or in the absence of quinones [Seaver04]. However, under regular growth conditions, it is not the primary source of intracellular hydrogen peroxide [Seaver04]. NDH-2 also has cupric reductase activity that is dependend on FAD or quinones. Under experimental conditions, the reductase activity was observed simultaneously with the dehydrogenase function linked to the respiratory chain [Rapisarda99]. NDH-2 mutants are more sensitive to copper toxicity; NDH-2 may have a role in copper homeostasis [RodriguezMontel06, Volentini11].

Sequence analysis predicts that NDH-2 contains four domains: a FAD binding domain containing a conserved FAD binding motif; and NADH binding domain with a conserved NADH binding motif, a membrane anchoring domain containing two predicted transmembrane regions and a copper binding domain containing two conserved cysteine residues that may be copper ligands [Rapisarda02]. Based on the remote similarity of NDH-2 to the SCOP family of FAD/NAD-linked reductases, a structural model of NDH-2 has been proposed [Schmid04].

The originally isolated ndh mutant [Young76] was not a single-locus mutant; it also contained a disruption of the nuo locus, encoding NDH-1 [Calhoun93]. Only strains containing mutations in both NADH dehydrogenases are unable to grow on mannitol as the sole source of carbon [Calhoun93]. Metabolic effects of an ndh null mutation alone and in combination with various other mutations have been investigated [Yun05].

Expression of ndh is repressed during anaerobic growth [Spiro89, Green94]. In an F1-ATPase-defective mutant, ndh transcription and NDH-2 activity is increased [Noda06].

Ndh: "NADH dehydrogenase" [Young76]

Reviews: [Melo04, Neijssel94, ECOSAL]

Citations: [Helling02, Noguchi04, Yagi91]

Locations: inner membrane

Map Position: [1,165,308 -> 1,166,612]

Molecular Weight of Polypeptide: 47.359 kD (from nucleotide sequence), 45.0 kD (experimental) [Young78 ]

pI: 9.06

Unification Links: ASAP:ABE-0003746 , CGSC:457 , DIP:DIP-10325N , EchoBASE:EB0643 , EcoGene:EG10649 , EcoliWiki:b1109 , ModBase:P00393 , OU-Microarray:b1109 , PortEco:ndh , PR:PRO_000023365 , Pride:P00393 , Protein Model Portal:P00393 , RefSeq:NP_415627 , RegulonDB:EG10649 , SMR:P00393 , String:511145.b1109 , UniProt:P00393

Relationship Links: InterPro:IN-FAMILY:IPR001327 , InterPro:IN-FAMILY:IPR013027 , InterPro:IN-FAMILY:IPR023753 , PDB:Structure:1OZK , Pfam:IN-FAMILY:PF00070 , Pfam:IN-FAMILY:PF07992 , Prints:IN-FAMILY:PR00368

Gene-Reaction Schematic: ?

GO Terms:

Biological Process: GO:0009060 - aerobic respiration Inferred from experiment [Tran97]
GO:0009061 - anaerobic respiration Inferred from experiment [Tran97]
GO:0019646 - aerobic electron transport chain Inferred from experiment [Matsushita87, Jaworowski81a]
GO:0055070 - copper ion homeostasis Inferred from experiment [RodriguezMontel06, Volentini11]
GO:0055114 - oxidation-reduction process Inferred by computational analysis [UniProtGOA11, GOA01]
Molecular Function: GO:0008137 - NADH dehydrogenase (ubiquinone) activity Inferred from experiment [Jaworowski81]
GO:0050660 - flavin adenine dinucleotide binding Inferred from experiment Inferred by computational analysis [GOA01, Hayashi89, Jaworowski81]
GO:0003954 - NADH dehydrogenase activity Inferred by computational analysis [GOA01a]
GO:0016491 - oxidoreductase activity Inferred by computational analysis [UniProtGOA11, GOA01]
Cellular Component: GO:0005886 - plasma membrane Inferred from experiment Inferred by computational analysis [UniProtGOA11a, UniProtGOA11, Jaworowski81, Young78]
GO:0030964 - NADH dehydrogenase complex Inferred from experiment [Jaworowski81]
GO:0005887 - integral component of plasma membrane Inferred by computational analysis [RodriguezMontel06]
GO:0016020 - membrane Inferred by computational analysis [UniProtGOA11]

MultiFun Terms: metabolism energy metabolism, carbon aerobic respiration
metabolism energy production/transport electron donors

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International


Enzymatic reaction of: NADH:ubiquinone oxidoreductase

Synonyms: NADH dehydrogenase

EC Number: 1.6.5.9

In Pathways: NADH to cytochrome bd oxidase electron transport II , NADH to cytochrome bo oxidase electron transfer II

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International

Summary:
Enzyme activity in vitro was generally measured with ubiquinone-1 as the electron acceptor. The physiological electron acceptor is expected to be ubiquinone-8.

The apparent Km for ubiquinone-1 is <5 µM. The enzyme has no detectable activity with NADPH as substrate [Jaworowski81a].

Cofactors or Prosthetic Groups: FAD [Comment 1, Jaworowski81, Thomson81, Campbell83, Hayashi89], Cu+ [Rapisarda02], Mg2+ [Hayashi89]

Kinetic Parameters:

Substrate
Km (μM)
Citations
NADH
34.0
[Bjorklof00]


Enzymatic reaction of: NADH cupric reductase (NADH:ubiquinone oxidoreductase II)

Synonyms: NADH-linked cupric reductase, cupric reductase

EC Number: 1.16.1.-

Cu2+ + NADH <=> Cu+ + NAD+ + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the direction in which it was curated.

Reversibility of this reaction is unspecified.

Credits:
Imported from EcoCyc 16-Sep-2014 by Paley S , SRI International

Summary:
The enzyme is specific for copper and does not reduce Fe(III) to Fe(II) [Rapisarda99].

Cofactors or Prosthetic Groups: FAD [Rapisarda99], Cu+ [Rapisarda02, Rapisarda02a]

Kinetic Parameters:

Substrate
Km (μM)
Citations
NADH
6.1
[Rapisarda02]
Cu2+
0.022
[Rapisarda02]


Sequence Features

Feature Class Location Citations Comment
Cleavage-of-Initial-Methionine 1
[Young81]
 
Chain 2 -> 434
[UniProt09]
UniProt: NADH dehydrogenase;
Protein-Segment 6 -> 121
[RodriguezMontel06]
FAD binding domain
Flavin-Binding-Region 7 -> 42
[RodriguezMontel06]
 
Nucleotide-Phosphate-Binding-Region 7 -> 42
[UniProt10]
UniProt: FAD; Non-Experimental Qualifier: by similarity;
Protein-Segment 170 -> 278
[RodriguezMontel06]
NADH binding region
Nucleotide-Phosphate-Binding-Region 171 -> 208
[UniProt10]
UniProt: NAD; Non-Experimental Qualifier: by similarity;
Protein-Binding-Region 305 -> 377
[RodriguezMontel06]
copper binding domain
Metal-Binding-Site 319, 316
[RodriguezMontel06]
predicted copper ligands

History:
10/20/97 Gene b1109 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10649; confirmed by SwissProt match.


References

Bjorklof00: Bjorklof K, Zickermann V, Finel M (2000). "Purification of the 45 kDa, membrane bound NADH dehydrogenase of Escherichia coli (NDH-2) and analysis of its interaction with ubiquinone analogues." FEBS Lett 467(1);105-10. PMID: 10664466

Calhoun93: Calhoun MW, Gennis RB (1993). "Demonstration of separate genetic loci encoding distinct membrane-bound respiratory NADH dehydrogenases in Escherichia coli." J Bacteriol 1993;175(10);3013-9. PMID: 8387992

Calhoun93a: Calhoun MW, Oden KL, Gennis RB, de Mattos MJ, Neijssel OM (1993). "Energetic efficiency of Escherichia coli: effects of mutations in components of the aerobic respiratory chain." J Bacteriol 175(10);3020-5. PMID: 8491720

Campbell83: Campbell HD, Young IG (1983). "Stereospecificity and requirements for activity of the respiratory NADH dehydrogenase of Escherichia coli." Biochemistry 22(25);5754-60. PMID: 6362717

ECOSAL: EcoSal "Escherichia coli and Salmonella: Cellular and Molecular Biology." Online edition.

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA01a: GOA, MGI (2001). "Gene Ontology annotation based on Enzyme Commission mapping." Genomics 74;121-128.

Green94: Green J, Guest JR (1994). "Regulation of transcription at the ndh promoter of Escherichia coli by FNR and novel factors." Mol Microbiol 12(3);433-44. PMID: 8065261

Hayashi89: Hayashi M, Miyoshi T, Takashina S, Unemoto T (1989). "Purification of NADH-ferricyanide dehydrogenase and NADH-quinone reductase from Escherichia coli membranes and their roles in the respiratory chain." Biochim Biophys Acta 977(1);62-9. PMID: 2679883

Helling02: Helling RB (2002). "Speed versus efficiency in microbial growth and the role of parallel pathways." J Bacteriol 184(4);1041-5. PMID: 11807064

Jaworowski81: Jaworowski A, Mayo G, Shaw DC, Campbell HD, Young IG (1981). "Characterization of the respiratory NADH dehydrogenase of Escherichia coli and reconstitution of NADH oxidase in ndh mutant membrane vesicles." Biochemistry 1981;20(12);3621-8. PMID: 7020757

Jaworowski81a: Jaworowski A, Campbell HD, Poulis MI, Young IG (1981). "Genetic identification and purification of the respiratory NADH dehydrogenase of Escherichia coli." Biochemistry 1981;20(7);2041-7. PMID: 6784762

Matsushita87: Matsushita K, Ohnishi T, Kaback HR (1987). "NADH-ubiquinone oxidoreductases of the Escherichia coli aerobic respiratory chain." Biochemistry 1987;26(24);7732-7. PMID: 3122832

Melo04: Melo AM, Bandeiras TM, Teixeira M (2004). "New insights into type II NAD(P)H:quinone oxidoreductases." Microbiol Mol Biol Rev 68(4);603-16. PMID: 15590775

Messner99: Messner KR, Imlay JA (1999). "The identification of primary sites of superoxide and hydrogen peroxide formation in the aerobic respiratory chain and sulfite reductase complex of Escherichia coli." J Biol Chem 274(15);10119-28. PMID: 10187794

Mileykovskaya93: Mileykovskaya EI, Dowhan W (1993). "Alterations in the electron transfer chain in mutant strains of Escherichia coli lacking phosphatidylethanolamine." J Biol Chem 268(33);24824-31. PMID: 8227044

Neijssel94: Neijssel OM, Teixeira de Mattos MJ (1994). "The energetics of bacterial growth: a reassessment." Mol Microbiol 13(2);172-82. PMID: 7984099

Noda06: Noda S, Takezawa Y, Mizutani T, Asakura T, Nishiumi E, Onoe K, Wada M, Tomita F, Matsushita K, Yokota A (2006). "Alterations of cellular physiology in Escherichia coli in response to oxidative phosphorylation impaired by defective F1-ATPase." J Bacteriol 188(19);6869-76. PMID: 16980490

Noguchi04: Noguchi Y, Nakai Y, Shimba N, Toyosaki H, Kawahara Y, Sugimoto S, Suzuki E (2004). "The energetic conversion competence of Escherichia coli during aerobic respiration studied by 31P NMR using a circulating fermentation system." J Biochem 136(4);509-15. PMID: 15625321

Poulis81: Poulis MI, Shaw DC, Campbell HD, Young IG (1981). "In vitro synthesis of the respiratory NADH dehydrogenase of Escherichia coli. Role of UUG as initiation codon." Biochemistry 20(14);4178-85. PMID: 7025892

Rapisarda02: Rapisarda VA, Chehin RN, De Las Rivas J, Rodriguez-Montelongo L, Farias RN, Massa EM (2002). "Evidence for Cu(I)-thiolate ligation and prediction of a putative copper-binding site in the Escherichia coli NADH dehydrogenase-2." Arch Biochem Biophys 405(1);87-94. PMID: 12176061

Rapisarda02a: Rapisarda VA, Volentini SI, Farias RN, Massa EM (2002). "Quenching of bathocuproine disulfonate fluorescence by Cu(I) as a basis for copper quantification." Anal Biochem 307(1);105-9. PMID: 12137786

Rapisarda99: Rapisarda VA, Montelongo LR, Farias RN, Massa EM (1999). "Characterization of an NADH-linked cupric reductase activity from the Escherichia coli respiratory chain." Arch Biochem Biophys 1999;370(2);143-50. PMID: 10510271

RodriguezMontel06: Rodriguez-Montelongo L, Volentini SI, Farias RN, Massa EM, Rapisarda VA (2006). "The Cu(II)-reductase NADH dehydrogenase-2 of Escherichia coli improves the bacterial growth in extreme copper concentrations and increases the resistance to the damage caused by copper and hydroperoxide." Arch Biochem Biophys 451(1);1-7. PMID: 16759635

RodriguezMontel95: Rodriguez-Montelongo L, Farias RN, Massa EM (1995). "Sites of electron transfer to membrane-bound copper and hydroperoxide-induced damage in the respiratory chain of Escherichia coli." Arch Biochem Biophys 323(1);19-26. PMID: 7487066

Schmid04: Schmid R, Gerloff DL (2004). "Functional properties of the alternative NADH:ubiquinone oxidoreductase from E. coli through comparative 3-D modelling." FEBS Lett 578(1-2);163-8. PMID: 15581635

Seaver04: Seaver LC, Imlay JA (2004). "Are respiratory enzymes the primary sources of intracellular hydrogen peroxide?." J Biol Chem 279(47);48742-50. PMID: 15361522

Sousa11: Sousa PM, Silva ST, Hood BL, Charro N, Carita JN, Vaz F, Penque D, Conrads TP, Melo AM (2011). "Supramolecular organizations in the aerobic respiratory chain of Escherichia coli." Biochimie 93(3);418-25. PMID: 21040753

Spiro89: Spiro S, Roberts RE, Guest JR (1989). "FNR-dependent repression of the ndh gene of Escherichia coli and metal ion requirement for FNR-regulated gene expression." Mol Microbiol 3(5);601-8. PMID: 2503680

Thomson81: Thomson JW, Shapiro BM (1981). "The respiratory chain NADH dehydrogenase of Escherichia coli. Isolation of an NADH:quinone oxidoreductase from membranes and comparison with the membrane-bound NADH:dichlorophenolindophenol oxidoreductase." J Biol Chem 256(6);3077-84. PMID: 7009604

Tran97: Tran QH, Bongaerts J, Vlad D, Unden G (1997). "Requirement for the proton-pumping NADH dehydrogenase I of Escherichia coli in respiration of NADH to fumarate and its bioenergetic implications." Eur J Biochem 244(1);155-60. PMID: 9063459

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.

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

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

Volentini11: Volentini SI, Farias RN, Rodriguez-Montelongo L, Rapisarda VA (2011). "Cu(II)-reduction by Escherichia coli cells is dependent on respiratory chain components." Biometals 24(5);827-35. PMID: 21390523

Yagi91: Yagi T (1991). "Bacterial NADH-quinone oxidoreductases." J Bioenerg Biomembr 23(2);211-25. PMID: 2050655

Young76: Young IG, Wallace BJ (1976). "Mutations affecting the reduced nicotinamide adenine dinucleotide dehydrogenase complex of Escherichia coli." Biochim Biophys Acta 449(3);376-85. PMID: 793616

Young78: Young IG, Jaworowski A, Poulis MI (1978). "Amplification of the respiratory NADH dehydrogenase of Escherichia coli by gene cloning." Gene 4(1);25-36. PMID: 365690

Young81: Young IG, Rogers BL, Campbell HD, Jaworowski A, Shaw DC (1981). "Nucleotide sequence coding for the respiratory NADH dehydrogenase of Escherichia coli. UUG initiation codon." Eur J Biochem 116(1);165-70. PMID: 6265208

Yun05: Yun NR, San KY, Bennett GN (2005). "Enhancement of lactate and succinate formation in adhE or pta-ackA mutants of NADH dehydrogenase-deficient Escherichia coli." J Appl Microbiol 99(6);1404-12. PMID: 16313413


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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
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