EzCatDB: D00043
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DB codeD00043
CATH domainDomain 12.40.30.10 : Elongation Factor Tu (Ef-tu); domain 3Catalytic domain
Domain 23.40.50.80 : Rossmann foldCatalytic domain
E.C.1.6.2.2
CSA1ndh

CATH domainRelated DB codes (homologues)
2.40.30.10 : Elongation Factor Tu (Ef-tu); domain 3M00006,M00141,M00159,M00164
3.40.50.80 : Rossmann foldM00006,M00141,M00159,M00164

Enzyme Name
UniProtKBKEGG

P83686P20070P00387
Protein nameNADH-cytochrome b5 reductase 3NADH-cytochrome b5 reductase 3NADH-cytochrome b5 reductase 3cytochrome-b5 reductase
cytochrome b5 reductase
dihydronicotinamide adenine dinucleotide-cytochrome b5 reductase
reduced nicotinamide adeninedinucleotide-cytochrome b5 reductase
NADH-ferricytochrome b5 oxidoreductase
NADH-cytochrome b5 reductase
NADH 5alpha-reductase
NADH-cytochrome-b5 reductase
SynonymsB5R
Cytochrome b5 reductase
EC 1.6.2.2
Diaphorase-1
B5R
Cytochrome b5 reductase
EC 1.6.2.2
Diaphorase-1
B5R
Cytochrome b5 reductase
EC 1.6.2.2
Diaphorase-1
ContainsNoneNADH-cytochrome b5 reductase 3 membrane-bound form
NADH-cytochrome b5 reductase 3 soluble form
NADH-cytochrome b5 reductase 3 membrane-bound form
NADH-cytochrome b5 reductase 3 soluble form
RefSeq
NP_620232.1 (Protein)
NM_138877.1 (DNA/RNA sequence)
NP_000389.1 (Protein)
NM_000398.6 (DNA/RNA sequence)
NP_001123291.1 (Protein)
NM_001129819.2 (DNA/RNA sequence)
NP_001165131.1 (Protein)
NM_001171660.1 (DNA/RNA sequence)
NP_001165132.1 (Protein)
NM_001171661.1 (DNA/RNA sequence)
NP_015565.1 (Protein)
NM_007326.4 (DNA/RNA sequence)
PfamPF00970 (FAD_binding_6)
PF00175 (NAD_binding_1)
[Graphical view]
PF00970 (FAD_binding_6)
PF00175 (NAD_binding_1)
[Graphical view]
PF00970 (FAD_binding_6)
PF00175 (NAD_binding_1)
[Graphical view]

KEGG pathways
MAP codePathways
MAP00530Aminosugars metabolism

UniProtKB:Accession NumberP83686P20070P00387
Entry nameNB5R3_PIGNB5R3_RATNB5R3_HUMAN
ActivityNADH + 2 ferricytochrome b5 = NAD(+) + H(+) + 2 ferrocytochrome b5.NADH + 2 ferricytochrome b5 = NAD(+) + H(+) + 2 ferrocytochrome b5.NADH + 2 ferricytochrome b5 = NAD(+) + H(+) + 2 ferrocytochrome b5.
SubunitComponent of a complex composed of cytochrome b5, NADH- cytochrome b5 reductase (CYB5R3) and MOSC2.Component of a complex composed of cytochrome b5, NADH- cytochrome b5 reductase (CYB5R3) and MOSC2 (By similarity).Component of a complex composed of cytochrome b5, NADH- cytochrome b5 reductase (CYB5R3) and MOSC2 (By similarity).
Subcellular locationEndoplasmic reticulum membrane, Lipid- anchor, Cytoplasmic side (By similarity). Mitochondrion outer membrane, Lipid-anchor, Cytoplasmic side (By similarity). Cytoplasm (By similarity). Note=The enzyme exists in two forms, a membrane-bound form on the cytoplasmic side of the endoplasmic reticulum and also on the mitochondrial outer membrane and in soluble form in erythrocytes (By similarity). NADH-cytochrome b5 reductase 3 membrane-bound form: Endoplasmic reticulum membrane, Lipid-anchor, Cytoplasmic side (By similarity). Mitochondrion outer membrane, Lipid-anchor, Cytoplasmic side (By similarity). NADH-cytochrome b5 reductase 3 soluble form: Cytoplasm (By similarity).Isoform 1: Endoplasmic reticulum membrane, Lipid-anchor, Cytoplasmic side. Mitochondrion outer membrane, Lipid-anchor, Cytoplasmic side.,Isoform 3: Cytoplasm. Note=Produces the soluble form found in erythrocytes.Isoform 1: Endoplasmic reticulum membrane, Lipid-anchor, Cytoplasmic side. Mitochondrion outer membrane, Lipid-anchor, Cytoplasmic side.,Isoform 2: Cytoplasm. Note=Produces the soluble form found in erythrocytes.
CofactorFAD.FAD.FAD.

Compound table: links to PDB-related databases & PoSSuM

CofactorsSubstratesProducts
KEGG-idC00016C00004C00996C00080C00003C00999
CompoundFADNADHFerricytochrome b5H+NAD+Ferrocytochrome b5
Typeamide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,nucleotideamide group,amine group,nucleotidearomatic ring (with nitrogen atoms),carbohydrate,heavy metalothersamide group,amine group,nucleotidearomatic ring (with nitrogen atoms),carbohydrate,heavy metal
ChEBI16238
16908

15378
15846

PubChem643975
439153

1038
5893

              
1ndhA01Bound:FADUnboundUnbound UnboundUnbound
1i7pA01Bound:FADUnboundUnbound UnboundUnbound
1ib0A01Bound:FADUnboundUnbound Bound:NADUnbound
1qx4A01Bound:FADUnboundUnbound UnboundUnbound
1qx4B01Bound:FADUnboundUnbound UnboundUnbound
1umkA01Bound:FADUnboundUnbound UnboundUnbound
1ndhA02UnboundUnboundUnbound UnboundUnbound
1i7pA02UnboundUnboundUnbound UnboundUnbound
1ib0A02UnboundUnboundUnbound UnboundUnbound
1qx4A02UnboundUnboundUnbound UnboundUnbound
1qx4B02UnboundUnboundUnbound UnboundUnbound
1umkA02UnboundUnboundUnbound UnboundUnbound

Active-site residues
resource
Swissprot;P83686 & literature [17]
pdbCatalytic residuesMain-chain involved in catalysiscomment
           
1ndhA01HIS 49;ARG 63;TYR 65
 
 
1i7pA01HIS 77;ARG 91;TYR 93
 
 
1ib0A01HIS 77;ARG 91;TYR 93
 
 
1qx4A01HIS 77;ARG 91;TYR 93
 
mutant S127P
1qx4B01HIS 77;ARG 91;TYR 93
 
mutant S127P
1umkA01HIS 77;ARG 91;TYR 93
 
 
1ndhA02 
PHE 272
 
1i7pA02 
PHE 300
 
1ib0A02 
PHE 300
 
1qx4A02 
PHE 300
 
1qx4B02 
PHE 300
 
1umkA02 
PHE 300
 

References for Catalytic Mechanism
ReferencesSectionsNo. of steps in catalysis
[12]p.39-40
[14]p.299-300
[17]

[19]Scheme II, p.3587-3588

references
[1]
PubMed ID3624234
JournalJ Biol Chem
Year1987
Volume262
Pages11801-2
AuthorsMiki K, Kaida S, Kasai N, Iyanagi T, Kobayashi K, Hayashi K
TitleCrystallization and preliminary x-ray crystallographic study of NADH-cytochrome b5 reductase from pig liver microsomes.
[2]
PubMed ID3656431
JournalJ Mol Biol
Year1987
Volume195
Pages749-50
AuthorsTakano T, Ogawa K, Sato M, Bando S, Yubisui T
TitlePreliminary X-ray data of NADH-cytochrome b5 reductase from human erythrocytes.
[3]
PubMed ID2831990
JournalBiochim Biophys Acta
Year1988
Volume953
Pages164-78
AuthorsUtecht RE, Kurtz DM Jr
TitleCytochrome b5 and NADH-cytochrome-b5 reductase from sipunculan erythrocytes; a methemerythrin reduction system from Phascolopsis gouldii.
[4]
PubMed ID2494940
JournalArch Biochem Biophys
Year1989
Volume270
Pages137-43
AuthorsReif DW, Coulombe RA Jr, Aust SD
TitleVanadate-dependent NAD(P)H oxidation by microsomal enzymes.
[5]
PubMed ID2189408
JournalBiochem Biophys Res Commun
Year1990
Volume168
Pages1285-91
AuthorsHyde GE, Campbell WH
TitleHigh-level expression in Escherichia coli of the catalytically active flavin domain of corn leaf NADH:nitrate reductase and its comparison to human NADH:cytochrome B5 reductase.
[6]
PubMed ID2123873
JournalJ Biol Chem
Year1990
Volume265
Pages21709-13
AuthorsStrittmatter P, Hackett CS, Korza G, Ozols J
TitleCharacterization of the covalent cross-links of the active sites of amidinated cytochrome b5 and NADH:cytochrome b5 reductase.
[7]
PubMed ID2019583
JournalJ Biol Chem
Year1991
Volume266
Pages7531-6
AuthorsShirabe K, Yubisui T, Nishino T, Takeshita M
TitleRole of cysteine residues in human NADH-cytochrome b5 reductase studied by site-directed mutagenesis. Cys-273 and Cys-283 are located close to the NADH-binding site but are not catalytically essential.
[8]
PubMed ID1898726
JournalJ Biol Chem
Year1991
Volume266
Pages66-70
AuthorsYubisui T, Shirabe K, Takeshita M, Kobayashi Y, Fukumaki Y, Sakaki Y, Takano T
TitleStructural role of serine 127 in the NADH-binding site of human NADH-cytochrome b5 reductase.
[9]
PubMed ID1370824
JournalJ Biol Chem
Year1992
Volume267
Pages2519-23
AuthorsStrittmatter P, Kittler JM, Coghill JE, Ozols J
TitleCharacterization of lysyl residues of NADH-cytochrome b5 reductase implicated in charge-pairing with active-site carboxyl residues of cytochrome b5 by site-directed mutagenesis of an expression vector for the flavoprotein.
[10]
CommentsX-ray crystallography
PubMed ID7893687
JournalBiochemistry
Year1995
Volume34
Pages2763-7
AuthorsNishida H, Inaka K, Yamanaka M, Kaida S, Kobayashi K, Miki K
TitleCrystal structure of NADH-cytochrome b5 reductase from pig liver at 2.4 A resolution.
Related PDB1ndh
[11]
PubMed ID7890048
JournalFEBS Lett
Year1995
Volume361
Pages97-100
AuthorsNishida H, Inaka K, Miki K
TitleSpecific arrangement of three amino acid residues for flavin-binding barrel structures in NADH-cytochrome b5 reductase and the other flavin-dependent reductases.
[12]
PubMed ID8880927
JournalProteins
Year1996
Volume26
Pages32-41
AuthorsNishida H, Miki K
TitleElectrostatic properties deduced from refined structures of NADH-cytochrome b5 reductase and the other flavin-dependent reductases: pyridine nucleotide-binding and interaction with an electron-transfer partner.
[13]
PubMed ID9602031
JournalBiochim Biophys Acta
Year1998
Volume1384
Pages16-22
AuthorsShirabe K, Nagai T, Yubisui T, Takeshita M
TitleElectrostatic interaction between NADH-cytochrome b5 reductase and cytochrome b5 studied by site-directed mutagenesis.
[14]
PubMed ID10082957
JournalBiochim Biophys Acta
Year1999
Volume1430
Pages290-301
AuthorsKimura S, Emi Y, Ikushiro S, Iyanagi T
TitleSystematic mutations of highly conserved His49 and carboxyl-terminal of recombinant porcine liver NADH-cytochrome b5 reductase solubilized domain.
[15]
PubMed ID10622712
JournalFEBS Lett
Year1999
Volume462
Pages283-8
AuthorsLamb DC, Kelly DE, Manning NJ, Kaderbhai MA, Kelly SL
TitleBiodiversity of the P450 catalytic cycle: yeast cytochrome b5/NADH cytochrome b5 reductase complex efficiently drives the entire sterol 14-demethylation (CYP51) reaction.
[16]
PubMed ID11695905
JournalBiochemistry
Year2001
Volume40
Pages13574-82
AuthorsBewley MC, Marohnic CC, Barber MJ
TitleThe structure and biochemistry of NADH-dependent cytochrome b5 reductase are now consistent.
Related PDB1i7p,1ib0
[17]
PubMed ID11574067
JournalJ Biochem (Tokyo)
Year2001
Volume130
Pages481-90
AuthorsKimura S, Nishida H, Iyanagi T
TitleEffects of flavin-binding motif amino acid mutations in the NADH-cytochrome b5 reductase catalytic domain on protein stability and catalysis.
[18]
PubMed ID14503867
JournalBiochemistry
Year2003
Volume42
Pages11170-82
AuthorsMarohnic CC, Bewley MC, Barber MJ
TitleEngineering and characterization of a NADPH-utilizing cytochrome b5 reductase.
[19]
PubMed ID12459552
JournalJ Biol Chem
Year2003
Volume278
Pages3580-9
AuthorsKimura S, Kawamura M, Iyanagi T
TitleRole of Thr(66) in porcine NADH-cytochrome b5 reductase in catalysis and control of the rate-limiting step in electron transfer.
[20]
PubMed ID14609324
JournalBiochemistry
Year2003
Volume42
Pages13145-51
AuthorsBewley MC, Davis CA, Marohnic CC, Taormina D, Barber MJ
TitleThe structure of the S127P mutant of cytochrome b5 reductase that causes methemoglobinemia shows the AMP moiety of the flavin occupying the substrate binding site.
Related PDB1qx4
[21]
PubMed ID15488472
JournalArch Biochem Biophys
Year2004
Volume431
Pages233-44
AuthorsDavis CA, Crowley LJ, Barber MJ
TitleCytochrome b5 reductase: the roles of the recessive congenital methemoglobinemia mutants P144L, L148P, and R159*.
[22]
PubMed ID15502298
JournalActa Crystallogr D Biol Crystallogr
Year2004
Volume60
Pages1929-34
AuthorsBando S, Takano T, Yubisui T, Shirabe K, Takeshita M, Nakagawa A
TitleStructure of human erythrocyte NADH-cytochrome b5 reductase.
Related PDB1umk


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2004-12-202009-02-26
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