DB code: M00006

CATH domain 3.40.50.360 : Rossmann fold
2.40.30.10 : Elongation Factor Tu (Ef-tu); domain 3 Catalytic domain
1.20.990.10 : NADPH-cytochrome p450 Reductase; Chain A, domain 3
3.40.50.80 : Rossmann fold Catalytic domain
E.C. 1.6.2.4
CSA 1amo
M-CSA 1amo
MACiE M0117

CATH domain Related DB codes (homologues)
1.20.990.10 : NADPH-cytochrome p450 Reductase; Chain A, domain 3 M00164
2.40.30.10 : Elongation Factor Tu (Ef-tu); domain 3 D00043 M00141 M00159 M00164
3.40.50.360 : Rossmann fold S00522 S00343 M00154
3.40.50.80 : Rossmann fold D00043 M00141 M00159 M00164

Uniprot Enzyme Name
UniprotKB Protein name Synonyms RefSeq Pfam
P00388 NADPH--cytochrome P450 reductase
CPR
P450R
EC 1.6.2.4
NP_113764.1 (Protein)
NM_031576.1 (DNA/RNA sequence)
PF00667 (FAD_binding_1)
PF00258 (Flavodoxin_1)
PF00175 (NAD_binding_1)
[Graphical View]
P16435 NADPH--cytochrome P450 reductase
CPR
P450R
EC 1.6.2.4
NP_000932.3 (Protein)
NM_000941.2 (DNA/RNA sequence)
PF00667 (FAD_binding_1)
PF00258 (Flavodoxin_1)
PF00175 (NAD_binding_1)
[Graphical View]

KEGG enzyme name
NADPH---hemoprotein reductase
CPR
FAD-cytochrome c reductase
NADP---cytochrome c reductase
NADP---cytochrome reductase
NADPH-dependent cytochrome c reductase
NADPH:P-450 reductase
NADPH:ferrihemoprotein oxidoreductase
NADPH---cytochrome P-450 oxidoreductase
NADPH---cytochrome c oxidoreductase
NADPH---cytochrome c reductase
NADPH---cytochrome p-450 reductase
NADPH---ferricytochrome c oxidoreductase
NADPH---ferrihemoprotein reductase
TPNH2 cytochrome c reductase
TPNH-cytochrome c reductase
aldehyde reductase (NADPH-dependent)
cytochrome P-450 reductase
cytochrome c reductase (reduced nicotinamide adenine dinucleotidephosphate, NADPH, NADPH-dependent)
dihydroxynicotinamide adenine dinucleotide phosphate-cytochrome creductase
ferrihemoprotein P-450 reductase
reduced nicotinamide adenine dinucleotide phosphate-cytochrome creductase
reductase, cytochrome c (reduced nicotinamide adenine dinucleotidephosphate)

UniprotKB: Accession Number Entry name Activity Subunit Subcellular location Cofactor
P16435 NCPR_HUMAN NADPH + n oxidized hemoprotein = NADP(+) + n reduced hemoprotein. Endoplasmic reticulum membrane, Peripheral membrane protein. Note=Anchored to the ER membrane by its N- terminal hydrophobic region. FAD. FMN.
P00388 NCPR_RAT NADPH + n oxidized hemoprotein = NADP(+) + n reduced hemoprotein. Endoplasmic reticulum membrane, Peripheral membrane protein. Note=Anchored to the ER membrane by its N- terminal hydrophobic region. FAD. FMN.

KEGG Pathways
Map code Pathways E.C.

Compound table
Cofactors Substrates Products Intermediates
KEGG-id C00061 C00016 C00005 C00080 C99999 C00923 C00006 C99999 C00924
E.C.
Compound FMN FAD NADPH H+ Oxidized hemoprotein Ferricytochrome NADP+ Reduced hemoprotein Ferrocytochrome
Type amide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,phosphate group/phosphate ion amide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,nucleotide amide group,amine group,nucleotide others aromatic ring (with nitrogen atoms),carboxyl group,heavy metal,peptide/protein aromatic ring (with nitrogen atoms),carboxyl group,heavy metal amide group,amine group,nucleotide aromatic ring (with nitrogen atoms),carboxyl group,heavy metal,peptide/protein aromatic ring (with nitrogen atoms),carboxyl group,heavy metal
ChEBI 17621
16238
16474
15378
18009
PubChem 643976
643975
5884
1038
5886
1amoA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FMN Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1amoB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FMN Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1j9zA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FMN Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1j9zB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FMN Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ja0A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FMN Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ja1A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FMN Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ja1B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FMN Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1b1cA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Bound:FMN Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1amoA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:FAD Unbound Unbound Unbound Analogue:NAP Unbound Unbound
1amoB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Analogue:FAD Unbound Unbound Unbound Analogue:NAP Unbound Unbound
1j9zA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:FAD Unbound Unbound Unbound Bound:NAP Unbound Unbound
1j9zB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:FAD Unbound Unbound Unbound Bound:NAP Unbound Unbound
1ja0A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:FAD Unbound Unbound Unbound Bound:NAP Unbound Unbound
1ja0B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:FAD Unbound Unbound Unbound Bound:NAP Unbound Unbound
1ja1A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:FAD Unbound Unbound Unbound Bound:NAP Unbound Unbound
1ja1B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Bound:FAD Unbound Unbound Unbound Bound:NAP Unbound Unbound
1amoA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1amoB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1j9zA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1j9zB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ja0A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ja0B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ja1A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ja1B03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1amoA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1amoB04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1j9zA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1j9zB04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ja0A04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ja0B03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ja1A04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound
1ja1B04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain Unbound Unbound Unbound Unbound Unbound Unbound Unbound Unbound

Reference for Active-site residues
resource references E.C.
literature [14]

Active-site residues
PDB Catalytic residues Cofactor-binding residues Modified residues Main-chain involved in catalysis Comment
1amoA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1amoB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1j9zA01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1j9zB01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ja0A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ja1A01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ja1B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1b1cA Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1amoA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 457
1amoB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 457
1j9zA02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 457
1j9zB02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 457
1ja0A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 457
1ja0B01 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain SER 457
1ja1A02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant S457A
1ja1B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain mutant S457A
1amoA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1amoB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1j9zA03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1j9zB03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ja0A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ja0B02 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ja1A03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1ja1B03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain
1amoA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 630;ASP 675
1amoB04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 630;ASP 675
1j9zA04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 630;ASP 675 mutant W677G
1j9zB04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 630;ASP 675 mutant W677G
1ja0A04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 630;ASP 675 deletion W677
1ja0B03 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain CYS 630;ASP 675 deletion W677
1ja1A04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ; mutant C630A, D675N
1ja1B04 Pdbj logo s Rasmollogo id Rasmollogo chain Mmcif id Mmcif chain ; mutant C630A, D675N

References for Catalytic Mechanism
References Sections No. of steps in catalysis
[1]
Fig.5, p.115
[4]
Fig.3, p.569-571
[9]
[10]
p.303-304
[12]
p.1962-1963
[14]
Fig.6, p.29169

References
[1]
Resource
Comments
Medline ID
PubMed ID 6326392
Journal Xenobiotica
Year 1984
Volume 14
Pages 105-18
Authors Capdevila J, Saeki Y, Falck JR
Title The mechanistic plurality of cytochrome P-450 and its biological ramifications.
Related PDB
Related UniProtKB
[2]
Resource
Comments
Medline ID
PubMed ID 3150357
Journal Int J Biochem
Year 1988
Volume 20
Pages 1189-96
Authors Iscan MY, Arinc E
Title Comparison of highly purified sheep liver and lung NADPH-cytochrome P-450 reductases by the analysis of kinetic and catalytic properties.
Related PDB
Related UniProtKB
[3]
Resource
Comments
Medline ID
PubMed ID 2708380
Journal J Biol Chem
Year 1989
Volume 264
Pages 7584-9
Authors Shen AL, Porter TD, Wilson TE, Kasper CB
Title Structural analysis of the FMN binding domain of NADPH-cytochrome P-450 oxidoreductase by site-directed mutagenesis.
Related PDB
Related UniProtKB
[4]
Resource
Comments
Medline ID
PubMed ID 8589067
Journal Biochimie
Year 1995
Volume 77
Pages 562-72
Authors Sevrioukova IF, Peterson JA
Title NADPH-P-450 reductase: structural and functional comparisons of the eukaryotic and prokaryotic isoforms.
Related PDB
Related UniProtKB
[5]
Resource
Comments
Medline ID
PubMed ID 7724541
Journal Proc Natl Acad Sci U S A
Year 1995
Volume 92
Pages 3214-8
Authors Djordjevic S, Roberts DL, Wang M, Shea T, Camitta MG, Masters BS, Kim JJ
Title Crystallization and preliminary x-ray studies of NADPH-cytochrome P450 reductase.
Related PDB
Related UniProtKB
[6]
Resource
Comments
Medline ID
PubMed ID 7644480
Journal Proc Natl Acad Sci U S A
Year 1995
Volume 92
Pages 7705-9
Authors Faulkner KM, Shet MS, Fisher CW, Estabrook RW
Title Electrocatalytically driven omega-hydroxylation of fatty acids using cytochrome P450 4A1.
Related PDB
Related UniProtKB
[7]
Resource
Comments
Medline ID
PubMed ID 8812989
Journal J Struct Biol
Year 1996
Volume 116
Pages 320-5
Authors Zhao Q, Smith G, Modi S, Paine M, Wolf RC, Tew D, Lian LY, Primrose WU, Roberts GC, Driessen HP
Title Crystallization and preliminary X-ray diffraction studies of human cytochrome P450 reductase.
Related PDB
Related UniProtKB
[8]
Resource
Comments
Medline ID
PubMed ID 9335117
Journal J Biomol NMR
Year 1997
Volume 10
Pages 63-75
Authors Barsukov I, Modi S, Lian LY, Sze KH, Paine MJ, Wolf CR, Roberts GC
Title 1H, 15N and 13C NMR resonance assignment, secondary structure and global fold of the FMN-binding domain of human cytochrome P450 reductase.
Related PDB
Related UniProtKB
[9]
Resource
Comments X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS)
Medline ID 97385116
PubMed ID 9237990
Journal Proc Natl Acad Sci U S A
Year 1997
Volume 94
Pages 8411-6
Authors Wang M, Roberts DL, Paschke R, Shea TM, Masters BS, Kim JJ
Title Three-dimensional structure of NADPH-cytochrome P450 reductase: prototype for FMN- and FAD-containing enzymes.
Related PDB 1amo
Related UniProtKB P00388
[10]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 61-241
Medline ID 99156068
PubMed ID 10048323
Journal Protein Sci
Year 1999
Volume 8
Pages 298-306
Authors Zhao Q, Modi S, Smith G, Paine M, McDonagh PD, Wolf CR, Tew D, Lian LY, Roberts GC, Driessen HP
Title Crystal structure of the FMN-binding domain of human cytochrome P450 reductase at 1.93 A resolution.
Related PDB 1b1c
Related UniProtKB P16435
[11]
Resource
Comments
Medline ID
PubMed ID 10961912
Journal Biochem Soc Trans
Year 2000
Volume 28
Pages 283-96
Authors Massey V
Title The chemical and biological versatility of riboflavin.
Related PDB
Related UniProtKB
[12]
Resource
Comments
Medline ID
PubMed ID 10995755
Journal J Biol Chem
Year 2000
Volume 275
Pages 39734-40
Authors Kitazume T, Takaya N, Nakayama N, Shoun H
Title Fusarium oxysporum fatty-acid subterminal hydroxylase (CYP505) is a membrane-bound eukaryotic counterpart of Bacillus megaterium cytochrome P450BM3.
Related PDB
Related UniProtKB
[13]
Resource
Comments
Medline ID
PubMed ID 11329262
Journal Biochemistry
Year 2001
Volume 40
Pages 1956-63
Authors Munro AW, Noble MA, Robledo L, Daff SN, Chapman SK
Title Determination of the redox properties of human NADPH-cytochrome P450 reductase.
Related PDB
Related UniProtKB
[14]
Resource
Comments X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF MUTANTS
Medline ID 21369908
PubMed ID 11371558
Journal J Biol Chem
Year 2001
Volume 276
Pages 29163-70
Authors Hubbard PA, Shen AL, Paschke R, Kasper CB, Kim JJ
Title NADPH-cytochrome P450 oxidoreductase. Structural basis for hydride and electron transfer.
Related PDB 1j9z 1ja0 1ja1
Related UniProtKB P00388

Comments
This enzyme catalyzes electron transfer from NADPH to other enzymes, microsomal cytochromes P450.
Of the two cofactors, FMN and FAD, FAD is involved in electron transfer (or hydride transfer) from the nicotinamide group of NADPH, according to the literature [14]. (The orientation of nicotinamide group in NAP (NADP) molecule in the PDB, 1ja1, is different from that in other PDB data, in which the group interacts with flavin of the FAD molecule. Thus, the PDB file, 1ja1, suggests a different stage from that of others.)
As the two flavin isoalloxazine rings of FAD and FMN are next to each other, the transferred electron might be transferred from FAD, to the substrate enzyme, through FMN (see [9]).

Created Updated
2004-10-19 2009-02-26