EzCatDB: M00006

DB codeM00006
CATH domainDomain 13.40.50.360
Domain 22.40.30.10Catalytic domain
Domain 31.20.990.10
Domain 43.40.50.80Catalytic domain
E.C.1.6.2.4
CSA1amo
MACiEM0117

CATH domainRelated DB codes (homologues)
1.20.990.10M00164
2.40.30.10D00043,M00141,M00159,M00164
3.40.50.360S00522,S00343,M00154
3.40.50.80D00043,M00141,M00159,M00164

Enzyme Name
Swiss-protKEGG

P00388P16435
Protein nameNADPH--cytochrome P450 reductaseNADPH--cytochrome P450 reductaseNADPH---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)
SynonymsCPR
P450R
EC 1.6.2.4
CPR
P450R
EC 1.6.2.4


Swiss-prot:Accession NumberP00388P16435
Entry nameNCPR_RATNCPR_HUMAN
ActivityNADPH + n oxidized hemoprotein = NADP(+) + n reduced hemoprotein.NADPH + n oxidized hemoprotein = NADP(+) + n reduced hemoprotein.
Subunit

Subcellular locationEndoplasmic reticulum membrane, Peripheral membrane protein. Note=Anchored to the ER membrane by its N- terminal hydrophobic region.Endoplasmic reticulum membrane, Peripheral membrane protein. Note=Anchored to the ER membrane by its N- terminal hydrophobic region.
CofactorFAD.,FMN.FAD.,FMN.


CofactorsSubstratesProducts
KEGG-idC00061C00016C00005C00080C99999C00923C00006C99999C00924
CompoundFMNFADNADPHH+Oxidized hemoproteinFerricytochromeNADP+Reduced hemoproteinFerrocytochrome
Typeamide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,phosphate group/phosphate ionamide group,amine group,aromatic ring (only carbon atom),aromatic ring (with nitrogen atoms),carbohydrate,nucleotideamide group,amine group,nucleotideothersaromatic ring (with nitrogen atoms),carboxyl group,heavy metal,peptide/proteinaromatic ring (with nitrogen atoms),carboxyl group,heavy metalamide group,amine group,nucleotidearomatic ring (with nitrogen atoms),carboxyl group,heavy metal,peptide/proteinaromatic ring (with nitrogen atoms),carboxyl group,heavy metal
1amoA01Bound:FMNUnboundUnbound
UnboundUnboundUnboundUnboundUnbound
1amoB01Bound:FMNUnboundUnbound
UnboundUnboundUnboundUnboundUnbound
1j9zA01Bound:FMNUnboundUnbound
UnboundUnboundUnboundUnboundUnbound
1j9zB01Bound:FMNUnboundUnbound
UnboundUnboundUnboundUnboundUnbound
1ja0A01Bound:FMNUnboundUnbound
UnboundUnboundUnboundUnboundUnbound
1ja1A01Bound:FMNUnboundUnbound
UnboundUnboundUnboundUnboundUnbound
1ja1B01Bound:FMNUnboundUnbound
UnboundUnboundUnboundUnboundUnbound
1b1cABound:FMNUnboundUnbound
UnboundUnboundUnboundUnboundUnbound
1amoA02UnboundBound:FADUnbound
UnboundUnboundAnalogue:NAPUnboundUnbound
1amoB02UnboundAnalogue:FADUnbound
UnboundUnboundAnalogue:NAPUnboundUnbound
1j9zA02UnboundBound:FADUnbound
UnboundUnboundBound:NAPUnboundUnbound
1j9zB02UnboundBound:FADUnbound
UnboundUnboundBound:NAPUnboundUnbound
1ja0A02UnboundBound:FADUnbound
UnboundUnboundBound:NAPUnboundUnbound
1ja0B01UnboundBound:FADUnbound
UnboundUnboundBound:NAPUnboundUnbound
1ja1A02UnboundBound:FADUnbound
UnboundUnboundBound:NAPUnboundUnbound
1ja1B02UnboundBound:FADUnbound
UnboundUnboundBound:NAPUnboundUnbound
1amoA03UnboundUnboundUnbound
UnboundUnboundUnboundUnboundUnbound
1amoB03UnboundUnboundUnbound
UnboundUnboundUnboundUnboundUnbound
1j9zA03UnboundUnboundUnbound
UnboundUnboundUnboundUnboundUnbound
1j9zB03UnboundUnboundUnbound
UnboundUnboundUnboundUnboundUnbound
1ja0A03UnboundUnboundUnbound
UnboundUnboundUnboundUnboundUnbound
1ja0B02UnboundUnboundUnbound
UnboundUnboundUnboundUnboundUnbound
1ja1A03UnboundUnboundUnbound
UnboundUnboundUnboundUnboundUnbound
1ja1B03UnboundUnboundUnbound
UnboundUnboundUnboundUnboundUnbound
1amoA04UnboundUnboundUnbound
UnboundUnboundUnboundUnboundUnbound
1amoB04UnboundUnboundUnbound
UnboundUnboundUnboundUnboundUnbound
1j9zA04UnboundUnboundUnbound
UnboundUnboundUnboundUnboundUnbound
1j9zB04UnboundUnboundUnbound
UnboundUnboundUnboundUnboundUnbound
1ja0A04UnboundUnboundUnbound
UnboundUnboundUnboundUnboundUnbound
1ja0B03UnboundUnboundUnbound
UnboundUnboundUnboundUnboundUnbound
1ja1A04UnboundUnboundUnbound
UnboundUnboundUnboundUnboundUnbound
1ja1B04UnboundUnboundUnbound
UnboundUnboundUnboundUnboundUnbound

Active-site residues
resource
literature [14]
pdbCatalytic residuescomment
1amoA01

1amoB01

1j9zA01

1j9zB01

1ja0A01

1ja1A01

1ja1B01

1b1cA

1amoA02SER 457

1amoB02SER 457

1j9zA02SER 457

1j9zB02SER 457

1ja0A02SER 457

1ja0B01SER 457

1ja1A02       
mutant S457A
1ja1B02       
mutant S457A
1amoA03

1amoB03

1j9zA03

1j9zB03

1ja0A03

1ja0B02

1ja1A03

1ja1B03

1amoA04CYS 630;ASP 675

1amoB04CYS 630;ASP 675

1j9zA04CYS 630;ASP 675
mutant W677G
1j9zB04CYS 630;ASP 675
mutant W677G
1ja0A04CYS 630;ASP 675
deletion W677
1ja0B03CYS 630;ASP 675
deletion W677
1ja1A04       ;       
mutant C630A, D675N
1ja1B04       ;       
mutant C630A, D675N

References for Catalytic Mechanism
ReferencesSectionsNo. 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]
PubMed ID6326392
JournalXenobiotica
Year1984
Volume14
Pages105-18
AuthorsCapdevila J, Saeki Y, Falck JR
TitleThe mechanistic plurality of cytochrome P-450 and its biological ramifications.
[2]
PubMed ID3150357
JournalInt J Biochem
Year1988
Volume20
Pages1189-96
AuthorsIscan MY, Arinc E
TitleComparison of highly purified sheep liver and lung NADPH-cytochrome P-450 reductases by the analysis of kinetic and catalytic properties.
[3]
PubMed ID2708380
JournalJ Biol Chem
Year1989
Volume264
Pages7584-9
AuthorsShen AL, Porter TD, Wilson TE, Kasper CB
TitleStructural analysis of the FMN binding domain of NADPH-cytochrome P-450 oxidoreductase by site-directed mutagenesis.
[4]
PubMed ID8589067
JournalBiochimie
Year1995
Volume77
Pages562-72
AuthorsSevrioukova IF, Peterson JA
TitleNADPH-P-450 reductase: structural and functional comparisons of the eukaryotic and prokaryotic isoforms.
[5]
PubMed ID7724541
JournalProc Natl Acad Sci U S A
Year1995
Volume92
Pages3214-8
AuthorsDjordjevic S, Roberts DL, Wang M, Shea T, Camitta MG, Masters BS, Kim JJ
TitleCrystallization and preliminary x-ray studies of NADPH-cytochrome P450 reductase.
[6]
PubMed ID7644480
JournalProc Natl Acad Sci U S A
Year1995
Volume92
Pages7705-9
AuthorsFaulkner KM, Shet MS, Fisher CW, Estabrook RW
TitleElectrocatalytically driven omega-hydroxylation of fatty acids using cytochrome P450 4A1.
[7]
PubMed ID8812989
JournalJ Struct Biol
Year1996
Volume116
Pages320-5
AuthorsZhao Q, Smith G, Modi S, Paine M, Wolf RC, Tew D, Lian LY, Primrose WU, Roberts GC, Driessen HP
TitleCrystallization and preliminary X-ray diffraction studies of human cytochrome P450 reductase.
[8]
PubMed ID9335117
JournalJ Biomol NMR
Year1997
Volume10
Pages63-75
AuthorsBarsukov I, Modi S, Lian LY, Sze KH, Paine MJ, Wolf CR, Roberts GC
Title1H, 15N and 13C NMR resonance assignment, secondary structure and global fold of the FMN-binding domain of human cytochrome P450 reductase.
[9]
CommentsX-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS)
Medline ID97385116
PubMed ID9237990
JournalProc Natl Acad Sci U S A
Year1997
Volume94
Pages8411-6
AuthorsWang M, Roberts DL, Paschke R, Shea TM, Masters BS, Kim JJ
TitleThree-dimensional structure of NADPH-cytochrome P450 reductase: prototype for FMN- and FAD-containing enzymes.
Related PDB1amo
Related Swiss-protP00388
[10]
CommentsX-RAY CRYSTALLOGRAPHY (1.93 ANGSTROMS) OF 61-241
Medline ID99156068
PubMed ID10048323
JournalProtein Sci
Year1999
Volume8
Pages298-306
AuthorsZhao Q, Modi S, Smith G, Paine M, McDonagh PD, Wolf CR, Tew D, Lian LY, Roberts GC, Driessen HP
TitleCrystal structure of the FMN-binding domain of human cytochrome P450 reductase at 1.93 A resolution.
Related PDB1b1c
Related Swiss-protP16435
[11]
PubMed ID10961912
JournalBiochem Soc Trans
Year2000
Volume28
Pages283-96
AuthorsMassey V
TitleThe chemical and biological versatility of riboflavin.
[12]
PubMed ID10995755
JournalJ Biol Chem
Year2000
Volume275
Pages39734-40
AuthorsKitazume T, Takaya N, Nakayama N, Shoun H
TitleFusarium oxysporum fatty-acid subterminal hydroxylase (CYP505) is a membrane-bound eukaryotic counterpart of Bacillus megaterium cytochrome P450BM3.
[13]
PubMed ID11329262
JournalBiochemistry
Year2001
Volume40
Pages1956-63
AuthorsMunro AW, Noble MA, Robledo L, Daff SN, Chapman SK
TitleDetermination of the redox properties of human NADPH-cytochrome P450 reductase.
[14]
CommentsX-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF MUTANTS
Medline ID21369908
PubMed ID11371558
JournalJ Biol Chem
Year2001
Volume276
Pages29163-70
AuthorsHubbard PA, Shen AL, Paschke R, Kasper CB, Kim JJ
TitleNADPH-cytochrome P450 oxidoreductase. Structural basis for hydride and electron transfer.
Related PDB1j9z,1ja0,1ja1
Related Swiss-protP00388

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]).

createdupdated
2004-10-192009-02-26
Copyright: Nozomi Nagano, JST & CBRC-AIST
Funded by PRESTO/Japan Science and Technology Corporation (JST) (December 2001 - November 2004)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2006)
Funded by Grant-in-Aid for Scientific Research (B)/Japan Society for the Promotion of Science (JSPS) (April 2005 - March 2008)
Funded by BIRD/Japan Science and Technology Corporation (JST) (September 2005 - September 2010)
Funded by BIRD/Japan Science and Technology Corporation (JST) (October 2007 - September 2010)
Funded by Grant-in-Aid for Publication of Scientific Research Results/Japan Society for the Promotion of Science (JSPS) (April 2011 - March 2012)

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