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Information on EC 1.6.2.4 - NADPH-hemoprotein reductase and Organism(s) Homo sapiens and UniProt Accession P16435
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1.6.2.4 NADPH-hemoprotein reductaseIUBMB Comments
A flavoprotein containing both FMN and FAD. This enzyme catalyses the transfer of electrons from NADPH, an obligatory two-electron donor, to microsomal P-450 monooxygenases (e.g. EC 1.14.14.1, unspecific monooxygenase) by stabilizing the one-electron reduced form of the flavin cofactors FAD and FMN. It also reduces cytochrome b5 and cytochrome c. The number n in the equation is 1 if the hemoprotein undergoes a 2-electron reduction, and is 2 if it undergoes a 1-electron reduction.
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Word Map
- 1.6.2.4
- monooxygenase
- heme
- quinone
- xenobiotics
- fmn
-
1.6.99.2
- flavoproteins
- dt-diaphorase
- phenobarbital
- cyp3a4
-
benzoapyrene
-
nadph:quinone
-
one-electron
-
drug-metabolizing
-
bioreductive
- 7-ethoxycoumarin
- semiquinone
- benzphetamine
-
two-electron
-
nadh-cytochrome
- aminopyrine
- cyp2c9
- 21-hydroxylase
- n-demethylase
-
o-deethylation
-
phenobarbital-induced
-
p-450-dependent
- 3-methylcholanthrene
- androstenedione
- adrenodoxin
- dicoumarol
- 7-ethoxyresorufin
- ethylmorphine
-
phenobarbital-treated
- beta-naphthoflavone
-
mixed-function
-
p-nitroanisole
-
p450-mediated
-
nitroreduction
-
p450-catalyzed
- 7,8-benzoflavone
-
omega-hydroxylation
- cyp21a2
- chlorzoxazone
-
o-dealkylation
-
virilization
- 17alpha-hydroxylase
-
6beta-hydroxylation
- biotechnology
- medicine
- bufuralol
-
2-amino-3-methylimidazo4,5-fquinoline
The taxonomic range for the selected organisms is: Homo sapiens
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
The expected taxonomic range for this enzyme is: Eukaryota, Bacteria, Archaea
Synonyms
nadph-cytochrome p-450 reductase, cytochrome p450 reductase, p450 reductase, p-450 reductase, nadph-p450 reductase, p450 bm3, p450 oxidoreductase, nadph cytochrome p450 reductase, cytochrome p450 oxidoreductase, cypor, 
more
topSYNONYM 
ORGANISM
UNIPROT
COMMENTARY 
LITERATURE
aldehyde reductase (NADPH-dependent)
-
-
-
-
CPR
cytochrome c reductase (reduced nicotinamide adenine dinucleotide phosphate, NADPH, NADPH-dependent)
-
-
-
-
cytochrome P450 reductase
-
-
dihydroxynicotinamide adenine dinucleotide phosphate-cytochrome c reductase
-
-
-
-
FAD-cytochrome c reductase
-
-
-
-
ferrihemprotein P450 reductase
-
-
-
-
NADP-cytochrome c reductase
-
-
-
-
NADP-cytochrome reductase
-
-
-
-
NADPH-cytochrome c oxidoreductase
-
-
-
-
NADPH-cytochrome c reductase
-
-
-
-
NADPH-cytochrome p-450 reductase
-
-
-
-
NADPH-cytochrome P450 (CYP) oxidoreductase
-
-
-
-
NADPH-cytochrome P450 reductase
-
-
NADPH-dependent cytochrome c reductase
-
-
-
-
NADPH-ferricytochrome c oxidoreductase
-
-
-
-
P450R
reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase
-
-
-
-
reductase, cytochrome c (reduced nicotinamide adenine dinucleotide phosphate)
-
-
-
-
TPNH-cytochrome c reductase
-
-
-
-
TPNH2 cytochrome c reductase
-
-
-
-
CPR
-
-
-
-
CPR
-
-
P450R
-
-
-
-
REACTION
REACTION DIAGRAM
COMMENTARY
ORGANISM
UNIPROT
LITERATURE
NADPH + H+ + n oxidized hemoprotein = NADP+ + n reduced hemoprotein
catalytic cycle and the rate-limiting step, which is at or after the introduction of the second electron from the reductase to the heme iron
-
REACTION TYPE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
redox reaction
-
-
-
-
oxidation
-
-
-
-
reduction
-
-
-
-
SYSTEMATIC NAME
IUBMB Comments
NADPH:hemoprotein oxidoreductase
A flavoprotein containing both FMN and FAD. This enzyme catalyses the transfer of electrons from NADPH, an obligatory two-electron donor, to microsomal P-450 monooxygenases (e.g. EC 1.14.14.1, unspecific monooxygenase) by stabilizing the one-electron reduced form of the flavin cofactors FAD and FMN. It also reduces cytochrome b5 and cytochrome c. The number n in the equation is 1 if the hemoprotein undergoes a 2-electron reduction, and is 2 if it undergoes a 1-electron reduction.
CAS REGISTRY NUMBER
COMMENTARY
9023-03-4
-
SUBSTRATE
PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2 ferricytochrome P450 + NADPH
2 ferrocytochrome P450 + NADP+ + H+
-
-
-
?
oxidized 2,6-dichlorophenolindophenol + NADPH + H+
reduced 2,6-dichlorophenolindophenol + NADP+
-
-
-
?
2,5-diaziridinyl-3-(hydroxymethyl)-6-methyl-1,4-benzoquinone + NADPH
NADP+ + ?
-
i.e. RH1, the enzyme reduces the antitumor drug RH1 to a semiquinone free radical. Following this reduction RH1 undergoes redox cycling under oxic conditions to produce potentially damaging hydroxyl radicals
-
-
?
NADPH + H+ + 1-[3-(4-phenoxyphenoxy)-2-oxopropyl]indole-5-carboxylic acid
NADP+ + 1-[2-hydroxy-3-(4-phenoxyphenoxy)propyl]indole-5-carboxylic acid
-
-
-
-
?
NADPH + H+ + ferricytochrome c
NADP+ + ferrocytochrome c
-
-
-
-
?
NADPH + H+ + oxidized 2,6-dichlorophenolindophenol
NADP+ + reduced 2,6-dichlorophenolindophenol
-
-
-
-
?
2 ferricytochrome c + NADH
2 ferrocytochrome c + NAD+ + H+
-
3-fold lower activity than with NADPH
-
-
?
2 ferricytochrome c + NADH
2 ferrocytochrome c + NAD+ + H+
-
low rate of internal electron transfer
-
-
?
2 ferricytochrome c + NADPH
2 ferrocytochrome c + NADP+ + H+
-
-
-
-
?
2 ferricytochrome P450 + NADPH
2 ferrocytochrome P450 + NADP+ + H+
-
-
-
-
?
2 ferricytochrome P450 + NADPH
2 ferrocytochrome P450 + NADP+ + H+
-
involved in drug metabolism
-
-
?
2 ferricytochrome P450 + NADPH
2 ferrocytochrome P450 + NADP+ + H+
-
involved in drug metabolism, reduced cytochrome P450 is essential for drug metabolism
-
-
?
ferricytochrome c + dithionite
ferrocytochrome c + ?
-
very low rate of internal electron transfer
-
-
?
additional information
?
-
-
coexpressed with CYP3A4 in insect cell lines, testosterone 6-beta-hydroxylase activity
-
-
?
additional information
?
-
-
coexpressed with two differently modified CYP2D6 cDNAs in Escherichia coli, functional recombinant monooxygenase, bufuralol and metoprolol metabolism
-
-
?
additional information
?
-
-
P450 Red does not contribute to the activation of RH1 (i.e. 2,5-diaziridinyl-3-(hydroxymethyl)-6-methyl-1,4-benzoquinone) in cells with normal P450 Red activity and plays only a minor role in activating this agent in cells with high levels of this enzyme
-
-
?
additional information
?
-
-
CYPOR is involved in reduction of the prodrug PR-104A
-
-
?
additional information
?
-
-
functional assays studying the effects of specific POR mutations on steroidogenesis shows that several POR variants impair CYP17A1, CYP21A2 and CYP19A1 activities to different degrees
-
-
?
additional information
?
-
-
P450R function is essential for cytochrome P450 activity. The enzyme provides the electrons used in P450-mediated reactions using NADPH as a cofactor. P450R-transfected MDA 231 breast cells display increased sensitivity to mitomycin C and 5-fluorouracil as compared to their empty-vector transfected counterparts. NADPH levels are decreased in P450R-overexpressing cells
-
-
?
additional information
?
-
-
the bioreductive agent RH1 can be reduced by the enzyme. RH1 produces DNA strand breaks and crosslinks in isolated DNA after reduction by P450 Red. P450 Red does not play a significant role in activating RH1 in cells with normal P450 Red activity
-
-
?
additional information
?
-
-
the enzyme donates electrons derived from NADPH to a variety of acceptor proteins, including squalene monooxygenase, 7-dehydro-cholesterol reductase, heme oxygenase, cytochrome b5 , and many microsomal cytochromes P450
-
-
?
additional information
?
-
-
binding of cytochrome P450 2B4 to cytochrome b5 and cytochrome P450 reductase, binding site on cytochrome P450 2B4 for its redox partners, complex formation modelling, overview
-
-
?
NATURAL SUBSTRATE
NATURAL PRODUCT
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate)
(Substrate)
LITERATURE
(Substrate)
(Substrate)
COMMENTARY
(Product)
(Product)
LITERATURE
(Product)
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
r=reversible
ir=irreversible
?=not specified
2 ferricytochrome P450 + NADPH
2 ferrocytochrome P450 + NADP+ + H+
-
-
-
?
2,5-diaziridinyl-3-(hydroxymethyl)-6-methyl-1,4-benzoquinone + NADPH
NADP+ + ?
-
i.e. RH1, the enzyme reduces the antitumor drug RH1 to a semiquinone free radical. Following this reduction RH1 undergoes redox cycling under oxic conditions to produce potentially damaging hydroxyl radicals
-
-
?
2 ferricytochrome P450 + NADPH
2 ferrocytochrome P450 + NADP+ + H+
-
-
-
-
?
2 ferricytochrome P450 + NADPH
2 ferrocytochrome P450 + NADP+ + H+
-
involved in drug metabolism
-
-
?
2 ferricytochrome P450 + NADPH
2 ferrocytochrome P450 + NADP+ + H+
-
involved in drug metabolism, reduced cytochrome P450 is essential for drug metabolism
-
-
?
additional information
?
-
-
P450 Red does not contribute to the activation of RH1 (i.e. 2,5-diaziridinyl-3-(hydroxymethyl)-6-methyl-1,4-benzoquinone) in cells with normal P450 Red activity and plays only a minor role in activating this agent in cells with high levels of this enzyme
-
-
?
additional information
?
-
-
CYPOR is involved in reduction of the prodrug PR-104A
-
-
?
additional information
?
-
-
functional assays studying the effects of specific POR mutations on steroidogenesis shows that several POR variants impair CYP17A1, CYP21A2 and CYP19A1 activities to different degrees
-
-
?
additional information
?
-
-
P450R function is essential for cytochrome P450 activity. The enzyme provides the electrons used in P450-mediated reactions using NADPH as a cofactor. P450R-transfected MDA 231 breast cells display increased sensitivity to mitomycin C and 5-fluorouracil as compared to their empty-vector transfected counterparts. NADPH levels are decreased in P450R-overexpressing cells
-
-
?
additional information
?
-
-
the bioreductive agent RH1 can be reduced by the enzyme. RH1 produces DNA strand breaks and crosslinks in isolated DNA after reduction by P450 Red. P450 Red does not play a significant role in activating RH1 in cells with normal P450 Red activity
-
-
?
additional information
?
-
-
the enzyme donates electrons derived from NADPH to a variety of acceptor proteins, including squalene monooxygenase, 7-dehydro-cholesterol reductase, heme oxygenase, cytochrome b5 , and many microsomal cytochromes P450
-
-
?
additional information
?
-
-
binding of cytochrome P450 2B4 to cytochrome b5 and cytochrome P450 reductase, binding site on cytochrome P450 2B4 for its redox partners, complex formation modelling, overview
-
-
?
COFACTOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
FAD
after replacement of all seven cysteine residues, no gross effect is observed on FMN and FAD binding and electron transfer from NADPH
FMN
after replacement of all seven cysteine residues, no gross effect is observed on FMN and FAD binding and electron transfer from NADPH
FAD
-
-
685178, 686913, 697616, 711112, 711152, 711717, 712406, 712656, 713542, 724112, 724127, 741764, 741778, 742083, 742864, 743656
FMN
-
-
685178, 686913, 697616, 711112, 711152, 711717, 712406, 712656, 713542, 724112, 724127, 741764, 741778, 742083, 742864, 743656
NADPH
-
-
288618, 657897, 657914, 658621, 658948, 659978, 672891, 686851, 686913, 689794, 711112, 711152, 711717, 712406, 712656, 713542, 713594, 724112, 724127, 743141
NADPH
-
NADPH mediates the interaction of CPR with a bilayer that mimics the endoplasmic reticulum. Without NADPH, CPR behaves as a peripheral protein. The introduction of NADPH transforms CPR to an integral membrane protein
additional information
-
cytochrome P450 reductase is a membrane-bound diflavin protein, which transfers two electrons sequentially from NADPH through FAD to the FMN cofactor, which is the ultimate donor of electrons to cytochrome P450 and other acceptor proteins
-
additional information
-
FAD accepts a hydride ion from NADPH, and reduced FAD donates electrons to FMN, which in turn transfers electrons to the heme center of cytochrome P450 oxygenase domain, electron transfer mechanism, structure, and redox potentials of the individual redox couples of FAD and FMN of CYPOR, overview. The FAD and FMN domains are connected by a flexible hinge region. The amino acids of the connecting domain are interspersed with the FNR-like domain. The connecting domain, composed mainly of alpha-helices, is tightly bound to the FNR-like domain, and together they form the FAD domain
-
METALS and IONS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
NaCl
optimum concentration 0.4-0.6 M, about 4fold activation for substrate ferricytochrome c
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
additional information
-
the herbal medicines Epimedii herba, Glycyrrhizae radix and Leonuri herba inhibit one or more NADPH-CYP reductase. Epimedii herba extract is the most potent inhibitor, IC50: 0.1859 mg/ml
-
additional information
-
at low molar ratios of cytochrome b5 to cytochrome P450 reductase, the more rapid catalysis results in enhanced substrate metabolism. In contrast, at high molar ratios of cytochome b5 to cytochrome P450 reductase, cytochrome b5 inhibits activity by binding to the proximal surface of cytochrome P450 and preventing the reductase from reducing ferric cytochrome P450 to the ferrous protein, thereby aborting the catalytic reaction cycle
-
additional information
-
no significant inhibition by diphenyleneiodonium chloride, flufenamic acid, and 18beta-glycyrrhetinic acid
-
ACTIVATING COMPOUND
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
2',5'-ADP
-
increases internal electron transfer in dithionite reduced enzyme
additional information
-
activity is upregulated upon exposure of the cells to melanoides from roasted malt
-
additional information
-
in contrast to the inhibitory effects of 2-chloroethyl ethyl sulfide on redox cycling b cytochrome P450 reductase, spontaneous hydrogen peroxide production by the enzyme is stimulated by 2-chloroethyl ethyl sulfide. This response is concentration-dependent in the range of 0.1-10 mM, reaching a maximum at 0.3 mM
-
additional information
-
at low molar ratios of cytochrome b5 to cytochrome P450 reductase, the more rapid catalysis results in enhanced substrate metabolism. In contrast, at high molar ratios of cytochome b5 to cytochrome P450 reductase, cytochrome b5 inhibits activity by binding to the proximal surface of cytochrome P450 and preventing the reductase from reducing ferric cytochrome P450 to the ferrous protein, thereby aborting the catalytic reaction cycle. Cytochrome b5 stimulates catalysis by causing a conformational change in the active site, which allows the active oxidizing oxyferryl species of cytochrome P450 to be formed more rapidly than in the presence of reductase
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
Ki VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
IMAGE
0.38
2-chloroethyl ethyl sulfide
Homo sapiens
-
using ferricytochrome c as cosubstrate, in 10 mM phosphate buffer (pH 7.4), at 37°C
8.6
2-chloroethyl ethyl sulfide
Homo sapiens
-
using oxidized 2,6-dichlorophenolindophenol as cosubstrate, in 10 mM phosphate buffer (pH 7.4), at 37°C
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
0.361
-
coexpression of 17alpha-2D6 + pJR7, supplementation of cultures with delta-aminolevulinic acid
0.414
-
coexpression of 17alpha-2D6 + pJR7, without supplementation of cultures with delta-aminolevulinic acid
0.517
-
coexpression of ompA-2D6 + pJR7, supplementation of cultures with delta-aminolevulinic acid
0.601
-
coexpression of ompA-2D6 + pJR7, without supplementation of cultures with delta-aminolevulinic acid
1.696
-
recombinant enzyme coexpressed with CYP3A4 in Spodoptera frugiperda cell lines
3.904
-
recombinant enzyme coexpressed with CYP3A4 in Trichoplusia ni cell lines
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
TEMPERATURE RANGE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
-
it is the relaxation to the thermodynamic equilibrium position between various two-electron reduced enzyme species, which is affected by both the pH value and the solvent and which decelerates with increasing pH
ORGANISM
COMMENTARY
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
SOURCE TISSUE
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SOURCE
LOCALIZATION
ORGANISM
UNIPROT
COMMENTARY
GeneOntology No.
LITERATURE
SOURCE
-
cytochrome b5 is a membrane-bound protein that is inserted into the membrane via an alpha-helix at its carboxy terminus. A random-coil linker of 15 amino acids connects the acidic soluble cytosolic heme domain to the membrane anchor
-
membrane-bound protein associated with the cytoplasmic side of the endoplasmic reticulum
-
CPR can exist as a peripheral membrane protein in the absence of NADPH and will transition to an integral membrane protein in the presence of stoichiometric amounts of NADPH or greater
-
-
-
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
metabolism
salt dependency of either cytochrome c or P450 reductions can be mostly attributed to a change in the conformational equilibrium of CPR. In the membrane bound form of wild-type CPR, the kobs value is lower than the one measured with the soluble form
evolution
-
the enzyme is a member of the diflavin oxidoreductase family. They are multi-domain enzymes containing distinct FAD and FMN domains connected by a flexible hinge. The protein has evolved by fusing two ancestral genes that encode proteins related to a FMN-containing flavodoxin and a FAD-containing ferredoxin-NADP+ oxidoreductase
malfunction
physiological function
additional information
malfunction
-
mutations in POR may reduce heme oxygenase-1 activity, potentially influencing heme catabolism in individuals carrying mutant POR alleles
malfunction
-
human patients with severe forms of CYPOR mutation show bone defects such as cranio- and humeroradial synostoses and long bone fractures, known as Antley-Bixler-like syndrome, ABS
physiological function
-
regulation of gap junction function by CYPOR, Cx43 may play an important role(s) in CYPOR-mediated bone defects seen in patients
physiological function
-
the enzyme is capable of activating molecular oxygen on its own merit, generating diffusible reduced oxygen species. It deplete peroxide via diffusible radical mediated process, thereby leading to the formation of water (but without significant evolution of oxygen). CPR mediated processes are bound to be energetically wasteful and potentially hazardous owing to the unavoidable nature of the CPR to generate and deplete diffusible reduced oxygen species. Molecular mechanisms of oxygen activation and peroxide depletion by CPR, overview
physiological function
-
the enzyme plays an important role in regulating all-trans-retinoic acid efficacy and CYP26A1 expression in HL-60 cells
additional information
-
cytochrome P450 reductase is a membrane-bound diflavin protein, which transfers two electrons sequentially from NADPH through FAD to the FMN cofactor, which is the ultimate donor of electrons to cytochrome P450 and other acceptor proteins
additional information
-
FAD accepts a hydride ion from NADPH, and reduced FAD donates electrons to FMN, which in turn transfers electrons to the heme center of cytochrome P450 oxygenase domain, electron transfer mechanism, overview. The two flavin domains undergo large domain movements during catalysis, domain-domain interactions, structure-activity analysis, overview
UNIPROT
ENTRY NAME
ORGANISM
NO. OF AA
NO. OF TRANSM. HELICES
MOLECULAR WEIGHT[Da]
SOURCE
SEQUENCE
LOCALIZATION PREDICTION
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable).
The reliability class of the localization prediction ranges from 1 (very reliable) to 5 (not reliable). NCPR_HUMAN
677
1
76690
Swiss-Prot
other Location (Reliability: 3)
PDB
SCOP
CATH
UNIPROT
ORGANISM
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
SUBUNIT
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
additional information
additional information
specific residues of the hinge segment are important in the control of the conformational equilibrium of CPR
additional information
-
domain-domain interactions, structure-activity analysis and structure comparisons, overview
CRYSTALLIZATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
structure of mutant DELTAD675/DELTAV676, the overall protein fold of the mutant structure is the same as the wild-type structure
PROTEIN VARIANTS
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
A635G/R636S
the mutations lead to a modest increase in cytochrome c reduction, which is linked to weaker coenzyme binding and faster interflavin electron transfer
D634A
the variant elicits a modest increase in coenzyme binding affinity coupled with a 36fold reduction in cytochrome c turnover and a 17fold decrease in the pre-steady state rate of flavin reduction
D634N
the variant elicits a modest increase in coenzyme binding affinity coupled with a 10fold reduction in cytochrome c turnover and a 3fold decrease in the pre-steady state rate of flavin reduction
DELTAD675/DELTAV676
tandem deletion variant, about 16% of wild-type activity
DELTAS678
deletion of Ser678 has no effect on cytochrome c reductase activity or Km values for NADPH or cytochrome c
DELTAV676
repositioning of Trp677 by deletion of Val676 decreases cytochrome c reductase activity, to about 6% of wild-type levels
G240P
mutation in the hinge segment, ionic strength profile is shifted to lower salt concentrations
I245A
mutation in the hinge segment, ionic strength profile is shifted to lower salt concentrations
I245A/R246A
mutation in the hinge segment, ionic strength profile is shifted to lower salt concentrations
I245P
mutation in the hinge segment, ionic strength profile is shifted to lower salt concentrations
I245R/R246I
mutation in the hinge segment, ionic strength profile is shifted to lower salt concentrations
R246A
mutation in the hinge segment, ionic strength profile is shifted to lower salt concentrations
R246P
mutation in the hinge segment, ionic strength profile is shifted to lower salt concentrations
R636A
the mutation leads to a modest increase in cytochrome c reduction, which is linked to weaker coenzyme binding and faster interflavin electron transfer
R636S
the mutation leads to a modest increase in cytochrome c reduction, which is linked to weaker coenzyme binding and faster interflavin electron transfer
S243P
mutation in the hinge segment, ionic strength profile is shifted to lower salt concentrations
W677A
substitution of Trp677 decreases NADPH-dependent cytochrome c reductase activity 25- to 55fold. W677A substitution abolishes the decrease in cytochrome c reductase activity at low pH
W677G
substitution of Trp677 decreases NADPH-dependent cytochrome c reductase activity 25- to 55fold. W677G substitution exhibits only a slight decrease in activity at low pH
W677G/S678X
W677G/S678X substitution exhibits only a slight decrease in activity at low pH
A115V
-
Vmax/Km for cytochrome c is 63% of wild-type value, Vmax/Km for NADPH is 41% of wild-type value
A287P
A457H
-
the POR mutant is associated with total loss of heme oxygenase-1 activity
A462T
-
vmax/Km for ferricytochrome c is 85% of the wild-type value. Vmax/Km for NADPH is 69% of the wild-type value
A485T
-
vmax/Km for ferricytochrome c is 36% of the wild-type value. Vmax/Km for NADPH is 51% of the wild-type value
A503V
C569Y
D211L
-
vmax/Km for ferricytochrome c is 27% of the wild-type value. Vmax/Km for NADPH is 59% of the wild-type value
delE53
-
vmax/Km for ferricytochrome c is 57% of the wild-type value. Vmax/Km for NADPH is 93% of the wild-type value
delT236_I242
-
either deletion of a 7 amino acid long segment or its replacement by polyproline repeats (5 and 10 residues) results in a significant increase in 2',5'-ADP enthalpy of binding. This is accompanied by a decrease in the number of thermodynamic microstates available for the ligand-cytochrome P450 reductase complex. The estimated heat capacity change for this interaction changes from -220 cal/mol*K in the wild-type enzyme to -580 cal/mol*K in the deletion mutant. Presteady-state kinetics measurements reveal a 50fold decrease in the microscopic rate for interdomain (FAD/FMN) electron transfer in the deletion mutant. Multiple turnover cytochome c reduction assays indicate that these mutations impair the ability of the FMN-binding domain to shuttle electrons from the FAD-binding domain to the cytochrome partner
delT236_I242ins(Pro)10
-
either deletion of a 7 amino acid long segment or its replacement by polyproline repeats (5 and 10 residues) results in a significant increase in 2',5'-ADP enthalpy of binding. This is accompanied by a decrease in the number of thermodynamic microstates available for the ligand-cytochrome P450 reductase complex
delT236_I242ins(Pro)5
-
either deletion of a 7 amino acid long segment or its replacement by polyproline repeats (5 and 10 residues) results in a significant increase in 2',5'-ADP enthalpy of binding. This is accompanied by a decrease in the number of thermodynamic microstates available for the ligand-cytochrome P450 reductase complex
E300K
-
vmax/Km for ferricytochrome c is 93% of the wild-type value. Vmax/Km for NADPH is 104% of the wild-type value
F646del
-
Vmax/Km for cytochrome c is 36% of wild-type value, Vmax/Km for NADPH is 94% of wild-type value
G213E
-
vmax/Km for ferricytochrome c is 111% of the wild-type value. Vmax/Km for NADPH is 105% of the wild-type value
G413S
G504R
G539R
-
Vmax/Km for cytochrome c is 9% of wild-type value, Vmax/Km for NADPH is 0.2% of wild-type value
H322Ala
-
the mutation does not affect the rate of NADPH hydride transfer or the FAD redox potentials, but does impede interflavin electron transfer. The mutant elicits a 4fold decrease in cytochrome c reduction and a 1.5fold decrease in ferricyanide reduction. The H322A substitution also leads to a modest increase in NADP(H) binding affinity, evidenced by a 2-3fold reduction in the Km for NADPH and Ki for NADP+
H322Q
-
the mutant shows a 50% decrease in cytochrome c and ferricyanide reduction and a marginal increase in NADP(H) binding affinity compared to the wild type enzyme
H628P
-
mutation results in similar disruption of CYP17A1 and CYP21A2 activities
L565P
-
Vmax/Km for cytochrome c is 14% of wild-type value, Vmax/Km for NADPH is 1.4% of wild-type value
M263V
-
Vmax/Km for cytochrome c is 76% of wild-type value, Vmax/Km for NADPH is 57% of wild-type value
P228L
P284L
-
vmax/Km for ferricytochrome c is 104% of the wild-type value. Vmax/Km for NADPH is 153% of the wild-type value
P284T
-
vmax/Km for ferricytochrome c is 16% of the wild-type value. Vmax/Km for NADPH is 32% of the wild-type value
P452L
-
vmax/Km for ferricytochrome c is 16% of the wild-type value. Vmax/Km for NADPH is 12% of the wild-type value
P55L
-
vmax/Km for ferricytochrome c is 67% of the wild-type value. Vmax/Km for NADPH is 123% of the wild-type value
Q153R
-
Vmax/Km for cytochrome c is 9% of wild-type value, Vmax/Km for NADPH is 11% of wild-type value
R316W
R406H
-
vmax/Km for ferricytochrome c is 62% of the wild-type value. Vmax/Km for NADPH is 78% of the wild-type value
R600W
-
vmax/Km for ferricytochrome c is 18% of the wild-type value. Vmax/Km for NADPH is 7% of the wild-type value
R616X
-
the POR mutant is associated with total loss of heme oxygenase-1 activity
S244C
-
mutation results in similar disruption of CYP17A1 and CYP21A2 activities
T142A
-
Vmax/Km for cytochrome c is 49% of wild-type value, Vmax/Km for NADPH is 52% of wild-type value
V472M
-
vmax/Km for ferricytochrome c is 23% of the wild-type value. Vmax/Km for NADPH is 24% of the wild-type value
V492E
V608F
V631I
-
Vmax/Km for cytochrome c is 74% of wild-type value, Vmax/Km for NADPH is 23% of wild-type value
W676H
-
rate of FAD-reduction is modestly affected, enzyme is reduced only to the two-electron level in rapid mixing experiments
Y181D
Y459H
additional information
A287P
-
Vmax/Km for cytochrome c is 9% of wild-type value, Vmax/Km for NADPH is 16% of wild-type value
A287P
-
the POR mutant is associated with 75-80% of normal heme oxygenase-1 activity
A503V
-
Vmax/Km for cytochrome c is 69% of wild-type value, Vmax/Km for NADPH is 86% of wild-type value
A503V
-
vmax/Km for ferricytochrome c is 67% of the wild-type value. Vmax/Km for NADPH is 56% of the wild-type value
A503V
-
the POR mutant is associated with close to wild type activity of heme oxygenase-1
C569Y
-
Vmax/Km for cytochrome c is 6% of wild-type value, Vmax/Km for NADPH is 2% of wild-type value
C569Y
-
the POR mutant is associated with 75-80% of normal heme oxygenase-1 activity
G413S
-
Vmax/Km for cytochrome c is 76% of wild-type value, Vmax/Km for NADPH is identical to wild-type value
G413S
-
the POR mutant is associated with close to wild type activity of heme oxygenase-1
G504R
-
Vmax/Km for cytochrome c is 53% of wild-type value, Vmax/Km for NADPH is 47% of wild-type value
G504R
-
the POR mutant is associated with close to wild type activity of heme oxygenase-1
P228L
-
Vmax/Km for cytochrome c is 75% of wild-type value, Vmax/Km for NADPH is 72% of wild-type value
P228L
-
the POR mutant is associated with close to wild type activity of heme oxygenase-1
R316W
-
Vmax/Km for cytochrome c is 61% of wild-type value, Vmax/Km for NADPH is 77% of wild-type value
R316W
-
the POR mutant is associated with close to wild type activity of heme oxygenase-1
V492E
-
mutation causes Antley-Bixler syndrome due to diminished binding of the FAD cofactor. Activity is restored by the addition of FAD
V492E
-
the POR mutant is associated with total loss of heme oxygenase-1 activity
V608F
-
Vmax/Km for cytochrome c is 8% of wild-type value, Vmax/Km for NADPH is 3% of wild-type value
V608F
-
the POR mutant is associated with 75-80% of normal heme oxygenase-1 activity
Y181D
-
mutation results in similar disruption of CYP17A1 and CYP21A2 activities
Y181D
-
the POR mutant is associated with total loss of heme oxygenase-1 activity
Y459H
-
mutation causes Antley-Bixler syndrome due to diminished binding of the FAD cofactor. Activity is restored by the addition of FAD
Y459H
-
the POR mutant is associated with total loss of heme oxygenase-1 activity
additional information
replacement of all seven cysteine residues, no gross effect is observed on FMN and FAD binding and electron transfer from NADPH. Cytochrome c reduction is decreased to 2% of wild-type. Introduction of Cys residues S9C, S32C, S55C, T668C to the Cys-less mutant shows substantial conformational changes upon membrane reconstitution of mutant, while liposome insertion has little effect on the T668C
additional information
specific residues of the hinge segment are important in the control of the conformational equilibrium of CPR. Mutations in residues G240, S243, I245 and R246 of the hinge segment, are capable of reducing cytochrome c yet with different efficiency and their maximal rates of cytochrome c reduction are shifted to lower salt concentration. Residue R246 seems to play a key role in a salt bridge network present at the interface of the hinge and the connecting domain
additional information
the deletion of more than 29 residues from the N-terminus of CYPOR decreases cytochrome P450 activity concomitant with alterations in electrophoretic mobility and an increased resistance to protease digestion. The altered kinetic properties of these mutants are consistent with electron transfer through random collisions rather than via formation of a stable CYPOR-P450 complex
additional information
-
chimeric protein: yeast FMN (residues 44-211) and human connecting/FAD (residues 232-677) domain
additional information
-
deletion of 11 amino acids of the membrane anchor yields a cytosolic protein that does not bind to the endoplasmic reticulum, whereas lengthening the membrane anchor by 5 amino acids causes the protein to be transported to the plasma membrane of COS cells
additional information
-
knock-down CYPOR in multiple osteoblast cell lines using RNAi technology decreasing the expression of Connexin 43, known to play a critical role in bone formation, modeling, and remodeling. Knock-down of CYPOR also decreases Gap Junction Intercellular Communication (GJIC) and hemichannel activity
GENERAL STABILITY
ORGANISM
UNIPROT
LITERATURE
STORAGE STABILITY
ORGANISM
UNIPROT
LITERATURE
-20°C, 50 mM Tris/HCl, pH 7.25, 1 mM EDTA, 50% glycerol, enzyme stored for less than 1 month prior to use
-
PURIFICATION (Commentary)
ORGANISM
UNIPROT
LITERATURE
2,5-ADP Sepharose affinitycolumn chromatography and DEAE anion exchange column chromatography
-
CLONED (Commentary)
ORGANISM
UNIPROT
LITERATURE
coexpressed together with a form of cytochrome P450 in Salmonella typhimurium TA1538
-
coexpression with CYP3A4 in Spodoptera frugiperda and Trichoplusia ni cell lines
-
coexpression with two differently modified CYP2D6 cDNAs in Escherichia coli, 17alpha-2D6 + pJR7 and ompA-2D6 + pJR7
-
expression of missense variant proteins lacking 27 N-terminal residues in Escherichia coli
-
truncated form lacking the membrane anchoring domain expresed in Escherichia coli BL21(DE3)pLysS
-
EXPRESSION
ORGANISM
UNIPROT
LITERATURE
the enzyme in acute myeloid leukemia cells is upregulated by all-trans-retinoic acid and by 1,25-dihydroxyvitamin D3 at the level of mRNA and protein
-
APPLICATION
ORGANISM
UNIPROT
COMMENTARY
LITERATURE
medicine
additional information
-
the CPR activity in different recombinant enzyme preparations is crucial for in vitro CYP3A5-mediated clearance of midazolam. The level of CPR affects both the affinity/binding of midazolam to the CYP enzyme and the velocity of the metabolic reaction
medicine
-
medical research, expression systems allows examinations on the activation of promutagenic drugs
medicine
-
presence of quercetin and (-)-epigallocatechin gallate in human diet may increase P-450 reductase activity during doxorubicin therapy (antitumour drug) with subsequent increased risk of toxicity
medicine
-
manifesting heterozygosity is a possible feature of P450 oxidoreductase deficiency
medicine
-
the POR genotype contributes to breast cancer risk among African American women
REF.
AUTHORS
TITLE
JOURNAL
VOL.
PAGES
YEAR
ORGANISM (UNIPROT)
PUBMED ID
SOURCE
Osawa, Y.; Higashiyama, T.; Nakamura, T.
Species specificity of estrogen biosynthesis in pregnancy. Immunochemical difference of placental NADPH-cytochrome c (P-450) reductase in human, baboon and horse
J. Steroid Biochem.
15
449-452
1981
Homo sapiens
Lee, C.A.; Kadwell, S.H.; Kost, T.A.; Serabjit-Singh, C.J.
CYP3A4 expressed by insect cells infected with a recombinant baculovirus containing both CYP3A4 and human NADPH-cytochrome P450 reductase is catalytically similar to human liver microsomal CYP3A4
Arch. Biochem. Biophys.
319
157-167
1995
Homo sapiens, Spodoptera frugiperda, Trichoplusia ni
Pritchard, M.P.; Glancey, M.J.; Blake, J.A.R.; Gilham, D.E.; Burchell, B.; Wolf, C.R.; Friedberg, T.
Functional co-expression of CYP2D6 and human NADPH-cytochrome P450 reductase in Escherichia coli
Pharmacogenetics
8
33-42
1998
Homo sapiens
Venkateswarlu, K.; Lamb, D.C.; Kelly, D.E.; Manning, N.J.; Kelly, S.L.
The N-terminal membrane domain of yeast NADPH-cytochrome P450 (CYP) oxidoreductase is not required for catalytic activity in steril biosynthesis or in reconstitution of CYP activity
J. Biol. Chem.
273
4492-4496
1998
Saccharomyces cerevisiae, Homo sapiens, Saccharomyces cerevisiae JL20
Gutierrez, A.; Grunau, A.; Paine, M.; Munro, A.W.; Wolf, C.R.; Roberts, G.C.; Scrutton, N.S.
Electron transfer in human cytochrome P450 reductase
Biochem. Soc. Trans.
31
497-501
2003
Homo sapiens
Munro, A.W.; Noble, M.A.; Robledo, L.; Daff, S.N.; Chapman, S.K.
Determination of the redox properties of human NADPH-cytochrome P450 reductase
Biochemistry
40
1956-1963
2003
Homo sapiens
Gutierrez, A.; Munro, A.W.; Grunau, A.; Wolf, C.R.; Scrutton, N.S.; Roberts, G.C.
Interflavin electron transfer in human cytochrome P450 reductase is enhanced by coenzyme binding. Relaxation kinetic studies with coenzyme analogues
Eur. J. Biochem.
270
2612-2621
2003
Homo sapiens
Faist, V.; Lindenmeier, M.; Geisler, C.; Erbersdobler, H.F.; Hofmann, T.
Influence of molecular weight fractions isolated from roasted malt on the enzyme activities of NADPH-cytochrome c-reductase and glutathione-S-transferase in Caco-2 cells
J. Agric. Food Chem.
50
602-606
2002
Homo sapiens
Yamazaki, Y.; Fujita, K.; Nakayama, K.; Suzuki, A.; Nakamura, K.; Yamazaki, H.; Kamataki, T.
Establishment of ten strains of genetically engineered Salmonella typhimurium TA1538 each co-expressing a form of human cytochrome P450 with NADPH-cytochrome P450 reductase sensitive to various promutagens
Mutat. Res.
562
151-162
2004
Homo sapiens
Dudka, J.
Decrease in NADPH-cytochrome P450 reductase activity of the human heart, liver and lungs in the presence of alpha-lipoic acid
Ann. Nutr. Metab.
50
121-125
2006
Homo sapiens
Dudka, J.; Jodynis-Liebert, J.; Korobowicz, E.; Burdan, F.; Korobowicz, A.; Szumilo, J.; Tokarska, E.; Klepacz, R.; Murias, M.
Activity of NADPH-cytochrome P-450 reductase of the human heart, liver and lungs in the presence of (-)-epigallocatechin gallate, quercetin and resveratrol: an in vitro study
Basic Clin. Pharmacol. Toxicol.
97
74-79
2005
Homo sapiens
Begleiter, A.; Leith, M.K.; Patel, D.; Hasinoff, B.B.
Role of NADPH cytochrome P450 reductase in activation of RH1
Cancer Chemother. Pharmacol.
60
713-723
2007
Homo sapiens
Kostrzewa-Nowak, D.; Paine, M.J.; Korytowska, A.; Serwatka, K.; Piotrowska, S.; Wolf, C.R.; Tarasiuk, J.
Bioreductive activation of mitoxantrone by NADPH cytochrome P450 reductase. Implications for increasing its ability to inhibit the growth of sensitive and multidrug resistant leukaemia HL60 cells
Cancer Lett.
245
252-262
2007
Homo sapiens
Hasinoff, B.B.; Begleiter, A.
The reductive activation of the antitumor drug RH1 to its semiquinone free radical by NADPH cytochrome P450 reductase and by HCT116 human colon cancer cells
Free Radic. Res.
40
974-978
2006
Homo sapiens
Liu, K.H.; Kim, M.J.; Jeon, B.H.; Shon, J.H.; Cha, I.J.; Cho, K.H.; Lee, S.S.; Shin, J.G.
Inhibition of human cytochrome P450 isoforms and NADPH-CYP reductase in vitro by 15 herbal medicines, including Epimedii herba
J. Clin. Pharm. Ther.
31
83-91
2006
Homo sapiens
Cheng, J.; Wan, D.F.; Gu, J.R.; Gong, Y.; Yang, S.L.; Hao, D.C.; Yang, L.
Establishment of a yeast system that stably expresses human cytochrome P450 reductase: application for the study of drug metabolism of cytochrome P450s in vitro
Protein Expr. Purif.
47
467-476
2006
Homo sapiens
Kranendonk, M.; Marohnic, C.C.; Panda, S.P.; Duarte, M.P.; Oliveira, J.S.; Masters, B.S.; Rueff, J.
Impairment of human CYP1A2-mediated xenobiotic metabolism by Antley-Bixler syndrome variants of cytochrome P450 oxidoreductase
Arch. Biochem. Biophys.
475
93-99
2008
Homo sapiens
Guise, C.P.; Wang, A.T.; Theil, A.; Bridewell, D.J.; Wilson, W.R.; Patterson, A.V.
Identification of human reductases that activate the dinitrobenzamide mustard prodrug PR-104A: a role for NADPH:cytochrome P450 oxidoreductase under hypoxia
Biochem. Pharmacol.
74
810-820
2007
Homo sapiens
Grunau, A.; Geraki, K.; Grossmann, J.G.; Gutierrez, A.
Conformational dynamics and the energetics of protein-ligand interactions: role of interdomain loop in human cytochrome P450 reductase
Biochemistry
46
8244-8255
2007
Homo sapiens
Haiman, C.A.; Setiawan, V.W.; Xia, L.Y.; Le Marchand, L.; Ingles, S.A.; Ursin, G.; Press, M.F.; Bernstein, L.; John, E.M.; Henderson, B.E.
A variant in the cytochrome p450 oxidoreductase gene is associated with breast cancer risk in African Americans
Cancer Res.
67
3565-3568
2007
Homo sapiens
Flueck, C.E.; Pandey, A.V.; Huang, N.; Agrawal, V.; Miller, W.L.
P450 oxidoreductase deficiency - a new form of congenital adrenal hyperplasia
Endocr. Dev.
13
67-81
2008
Homo sapiens
Brenner, S.; Hay, S.; Munro, A.W.; Scrutton, N.S.
Inter-flavin electron transfer in cytochrome P450 reductase - effects of solvent and pH identify hidden complexity in mechanism
FEBS J.
275
4540-4557
2008
Homo sapiens
Yao, H.T.; Chang, Y.W.; Lan, S.J.; Yeh, T.K.
The inhibitory effect of tannic acid on cytochrome P450 enzymes and NADPH-CYP reductase in rat and human liver microsomes
Food Chem. Toxicol.
46
645-653
2008
Homo sapiens, Rattus norvegicus
Flck, C.E.; Nicolo, C.; Pandey, A.V.
Clinical, structural and functional implications of mutations and polymorphisms in human NADPH P450 oxidoreductase
Fundam. Clin. Pharmacol.
21
399-410
2007
Homo sapiens
Scott, R.R.; Gomes, L.G.; Huang, N.; Van Vliet, G.; Miller, W.L.
Apparent manifesting heterozygosity in P450 oxidoreductase deficiency and its effect on coexisting 21-hydroxylase deficiency
J. Clin. Endocrinol. Metab.
92
2318-2322
2007
Homo sapiens
Dhir, V.; Ivison, H.E.; Krone, N.; Shackleton, C.H.; Doherty, A.J.; Stewart, P.M.; Arlt, W.
Differential inhibition of CYP17A1 and CYP21A2 activities by the P450 oxidoreductase mutant A287P
Mol. Endocrinol.
21
1958-1968
2007
Homo sapiens
Huang, N.; Agrawal, V.; Giacomini, K.M.; Miller, W.L.
Genetics of P450 oxidoreductase: sequence variation in 842 individuals of four ethnicities and activities of 15 missense mutations
Proc. Natl. Acad. Sci. USA
105
1733-1738
2008
Homo sapiens
Martinez, V.G.; Williams, K.J.; Stratford, I.J.; Clynes, M.; OConnor, R.
Overexpression of cytochrome P450 NADPH reductase sensitises MDA 231 breast carcinoma cells to 5-fluorouracil: possible mechanisms involved
Toxicol. In Vitro
22
582-588
2008
Homo sapiens
Gan, L.; von Moltke, L.L.; Trepanier, L.A.; Harmatz, J.S.; Greenblatt, D.J.; Court, M.H.
Role of NADPH-cytochrome P450 reductase and cytochrome-b5/NADH-b5 reductase in variability of CYP3A activity in human liver microsomes
Drug Metab. Dispos.
37
90-96
2009
Homo sapiens
Aigrain, L.; Pompon, D.; Morera, S.; Truan, G.
Structure of the open conformation of a functional chimeric NADPH cytochrome P450 reductase
EMBO Rep.
10
742-747
2009
Homo sapiens, Saccharomyces cerevisiae (P16603)
Iijima, S.; Ohishi, A.; Ohzeki, T.
Cytochrome P450 oxidoreductase deficiency with Antley-Bixler syndrome: steroidogenic capacities
J. Pediatr. Endocrinol. Metab.
22
469-475
2009
Homo sapiens
Gomes, A.M.; Winter, S.; Klein, K.; Turpeinen, M.; Schaeffeler, E.; Schwab, M.; Zanger, U.M.
Pharmacogenomics of human liver cytochrome P450 oxidoreductase: multifactorial analysis and impact on microsomal drug oxidation
Pharmacogenomics
10
579-599
2009
Homo sapiens (P16435), Homo sapiens
Inaoka, Y.; Yazawa, T.; Mizutani, T.; Kokame, K.; Kangawa, K.; Uesaka, M.; Umezawa, A.; Miyamoto, K.
Regulation of P450 oxidoreductase by gonadotropins in rat ovary and its effect on estrogen production
Reprod. Biol. Endocrinol.
6
62
2008
Rattus norvegicus (P00388), Homo sapiens (P16435), Homo sapiens
Pandey, A.V.; Flueck, C.E.; Mullis, P.E.
Altered heme catabolism by heme oxygenase-1 caused by mutations in human NADPH cytochrome P450 reductase
Biochem. Biophys. Res. Commun.
400
374-378
2010
Homo sapiens
Farooq, Y.; Roberts, G.C.
Kinetics of electron transfer between NADPH-cytochrome P450 reductase and cytochrome P450 3A4
Biochem. J.
432
485-493
2010
Homo sapiens
Feidt, D.M.; Klein, K.; Nuessler, A.; Zanger, U.M.
RNA-interference approach to study functions of NADPH: cytochrome P450 oxidoreductase in human hepatocytes
Chem. Biodivers.
6
2084-2091
2009
Homo sapiens
Ellis, J.; Gutierrez, A.; Barsukov, I.L.; Huang, W.C.; Grossmann, J.G.; Roberts, G.C.
Domain motion in cytochrome P450 reductase: conformational equilibria revealed by NMR and small-angle X-ray scattering
J. Biol. Chem.
284
36628-36637
2009
Homo sapiens
Bumpus, N.N.; Hollenberg, P.F.
Cross-linking of human cytochrome P450 2B6 to NADPH-cytochrome P450 reductase: Identification of a potential site of interaction
J. Inorg. Biochem.
104
485-488
2010
Homo sapiens
Flueck, C.E.; Mullis, P.E.; Pandey, A.V.
Modeling of human P450 oxidoreductase structure by in silico mutagenesis and MD simulation
Mol. Cell. Endocrinol.
313
17-22
2009
Rattus norvegicus (P00388), Homo sapiens (P16435), Homo sapiens
Gray, J.P.; Mishin, V.; Heck, D.E.; Laskin, D.L.; Laskin, J.D.
Inhibition of NADPH cytochrome P450 reductase by the model sulfur mustard vesicant 2-chloroethyl ethyl sulfide is associated with increased production of reactive oxygen species
Toxicol. Appl. Pharmacol.
247
76-82
2010
Homo sapiens, Mus musculus, Rattus norvegicus
Christensen, H.; Hestad, A.L.; Molden, E.; Mathiesen, L.
CYP3A5-mediated metabolism of midazolam in recombinant systems is highly sensitive to NADPH-cytochrome P450 reductase activity
Xenobiotica
41
1-5
2011
Homo sapiens
Im, S.C.; Waskell, L.
The interaction of microsomal cytochrome P450 2B4 with its redox partners, cytochrome P450 reductase and cytochrome b5
Arch. Biochem. Biophys.
507
144-153
2011
Homo sapiens
Iyanagi, T.; Xia, C.; Kim, J.J.
NADPH-cytochrome P450 oxidoreductase: prototypic member of the diflavin reductase family
Arch. Biochem. Biophys.
528
72-89
2012
Homo sapiens, Rattus norvegicus
Polusani, S.R.; Kar, R.; Riquelme, M.A.; Masters, B.S.; Panda, S.P.
Regulation of gap junction function and Connexin 43 expression by cytochrome P450 oxidoreductase (CYPOR)
Biochem. Biophys. Res. Commun.
411
490-495
2011
Homo sapiens, Mus musculus
Manoj, K.M.; Gade, S.K.; Mathew, L.
Cytochrome P450 reductase: a harbinger of diffusible reduced oxygen species
PLoS ONE
5
e13272
2010
Homo sapiens
Meints, C.E.; Parke, S.M.; Wolthers, K.R.
Proximal FAD histidine residue influences interflavin electron transfer in cytochrome P450 reductase and methionine synthase reductase
Arch. Biochem. Biophys.
547
18-26
2014
Homo sapiens
Whitelaw, D.A.; Tonkin, R.; Meints, C.E.; Wolthers, K.R.
Kinetic analysis of electron flux in cytochrome P450 reductases reveals differences in rate-determining steps in plant and mammalian enzymes
Arch. Biochem. Biophys.
584
107-115
2015
Arabidopsis thaliana, Homo sapiens, Artemisia annua
Mothersole, R.G.; Meints, C.E.; Louder, A.; Wolthers, K.R.
Role of active site loop in coenzyme binding and flavin reduction in cytochrome P450 reductase
Arch. Biochem. Biophys.
606
111-119
2016
Homo sapiens (P16435), Homo sapiens
Lehr, M.; Fabian, J.; Hanekamp, W.
Involvement of microsomal NADPH-cytochrome P450 reductase in metabolic reduction of drug ketones
Biopharm. Drug Dispos.
36
398-404
2015
Homo sapiens
Spencer, A.L.; Bagai, I.; Becker, D.F.; Zuiderweg, E.R.; Ragsdale, S.W.
Protein/protein interactions in the mammalian heme degradation pathway heme oxygenase-2, cytochrome P450 reductase, and biliverdin reductase
J. Biol. Chem.
289
29836-29858
2014
Homo sapiens
Hu, L.; Lv, J.F.; Zhuo, W.; Zhang, C.M.; Zhou, H.H.; Fan, L.
Effect of NADPH-cytochrome P450 reductase on all-trans-retinoic acid efficacy and cytochrome P450 26A1 expression in human myeloid leukaemia HL-60 cells
J. Pharm. Pharmacol.
68
1193-1202
2016
Homo sapiens
Gocek, E.; Marchwicka, A.; Bujko, K.; Marcinkowska, E.
NADPH-cytochrome P450 reductase is regulated by all-trans retinoic acid and by 1,25-dihydroxyvitamin D3 in human acute myeloid leukemia cells
PLoS ONE
9
e91752
2014
Homo sapiens
Hubbard, P.A.; Xia, C.; Shen, A.L.; Kim, J.P.
Structural and kinetic investigations of the carboxy terminus of NADPH-cytochrome P450 oxidoreductase
Arch. Biochem. Biophys.
701
108792
2021
Homo sapiens (P16435)
Xia, C.; Shen, A.L.; Duangkaew, P.; Kotewong, R.; Rongnoparut, P.; Feix, J.; Kim, J.P.
Structural and functional studies of the membrane-binding domain of NADPH-cytochrome P450 oxidoreductase
Biochemistry
58
2408-2418
2019
Homo sapiens (P16435)
Campelo, D.; Lautier, T.; Urban, P.; Esteves, F.; Bozonnet, S.; Truan, G.; Kranendonk, M.
The hinge segment of human NADPH-cytochrome P450 reductase in conformational switching The critical role of ionic strength
Front. Pharmacol.
8
755
2017
Homo sapiens (P16435)
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