Function and Biology

THREE-DIMENSIONAL STRUCTURE OF NADPH-CYTOCHROME P450 REDUCTASE: PROTOTYPE FOR FMN-AND FAD-CONTAINING ENZYMES

Source organism: Rattus norvegicus
Biochemical function: enzyme binding
Biological process: oxidation-reduction process
Cellular component: integral component of membrane

EC 1.6.2.4: NADPH--hemoprotein reductase

Reaction catalysed:
NADPH + n oxidized hemoprotein = NADP(+) + n reduced hemoprotein.
Comments:
  • This enzyme catalyzes the transfer of electrons from NADPH, an obligatory two-electron donor, to microsomal P450 monooxygenases (e.g. EC 1.14.14.1) 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.
Systematic name:
NADPH:hemoprotein oxidoreductase
Alternative Name(s):
  • 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
  • TPNH(2) cytochrome c reductase
  • TPNH-cytochrome c reductase
  • Aldehyde reductase (NADPH-dependent)
  • Cytochrome P-450 reductase
  • Cytochrome c reductase (reduced nicotinamide adenine dinucleotide phosphate, NADPH, NADPH-dependent)
  • Dihydroxynicotinamide adenine dinucleotide phosphate-cytochrome c reductase
  • Ferrihemoprotein P-450 reductase
  • Reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase
  • Reductase, cytochrome c (reduced nicotinamide adenine dinucleotide phosphate)
  • Cytochrome P450 reductase
  • NADPH--cytochrome P450 reductase
  • NADPH--cytochrome P450 oxidoreductase
  • NADPH:P450 reductase
  • POR

GO terms

Biochemical function:
Biological process:
Cellular component:

Sequence families

Pfam Protein families (Pfam)
PF00175
Domain description: Oxidoreductase NAD-binding domain
Occurring in:
  1. NADPH--cytochrome P450 reductase
1 copy of Pfam domain PF00175 (Oxidoreductase NAD-binding domain) in NADPH--cytochrome P450 reductase in PDB 1amo.

PF00667
Domain description: FAD binding domain
Occurring in:
  1. NADPH--cytochrome P450 reductase
1 copy of Pfam domain PF00667 (FAD binding domain) in NADPH--cytochrome P450 reductase in PDB 1amo.

PF00258
Domain description: Flavodoxin
Occurring in:
  1. NADPH--cytochrome P450 reductase
1 copy of Pfam domain PF00258 (Flavodoxin) in NADPH--cytochrome P450 reductase in PDB 1amo.

InterPro InterPro annotations
IPR001709
Domain description: Flavoprotein pyridine nucleotide cytochrome reductase
Occurring in:
  1. NADPH--cytochrome P450 reductase
IPR001094
Domain description: Flavodoxin-like
Occurring in:
  1. NADPH--cytochrome P450 reductase
IPR023208
Domain description: NADPH-cytochrome P450 reductase
Occurring in:
  1. NADPH--cytochrome P450 reductase
IPR008254
Domain description: Flavodoxin/nitric oxide synthase
Occurring in:
  1. NADPH--cytochrome P450 reductase
IPR029039
Domain description: Flavoprotein-like superfamily
Occurring in:
  1. NADPH--cytochrome P450 reductase
IPR017927
Domain description: Ferredoxin reductase-type FAD-binding domain
Occurring in:
  1. NADPH--cytochrome P450 reductase
IPR001433
Domain description: Oxidoreductase FAD/NAD(P)-binding
Occurring in:
  1. NADPH--cytochrome P450 reductase
IPR017938
Domain description: Riboflavin synthase-like beta-barrel
Occurring in:
  1. NADPH--cytochrome P450 reductase
IPR003097
Domain description: FAD-binding, type 1
Occurring in:
  1. NADPH--cytochrome P450 reductase

Structure domains

CATH CATH domains
2.40.30.10
Class: Mainly Beta
Architecture: Beta Barrel
Topology: Elongation Factor Tu (Ef-tu); domain 3
Homology: Translation factors
Occurring in:
  1. NADPH--cytochrome P450 reductase
1 copy of CATH domain 2.40.30.10 (Elongation Factor Tu (Ef-tu); domain 3) in NADPH--cytochrome P450 reductase in PDB 1amo.
3.40.50.80
Class: Alpha Beta
Architecture: 3-Layer(aba) Sandwich
Topology: Rossmann fold
Homology: Nucleotide-binding domain of ferredoxin-NADP reductase (FNR) module
Occurring in:
  1. NADPH--cytochrome P450 reductase
1 copy of CATH domain 3.40.50.80 (Rossmann fold) in NADPH--cytochrome P450 reductase in PDB 1amo.
3.40.50.360
Class: Alpha Beta
Architecture: 3-Layer(aba) Sandwich
Topology: Rossmann fold
Homology: Rossmann fold
Occurring in:
  1. NADPH--cytochrome P450 reductase
1 copy of CATH domain 3.40.50.360 (Rossmann fold) in NADPH--cytochrome P450 reductase in PDB 1amo.
1.20.990.10
Class: Mainly Alpha
Architecture: Up-down Bundle
Topology: NADPH-cytochrome p450 Reductase; Chain A, domain 3
Homology: NADPH-cytochrome p450 Reductase; Chain A, domain 3
Occurring in:
  1. NADPH--cytochrome P450 reductase
1 copy of CATH domain 1.20.990.10 (NADPH-cytochrome p450 Reductase; Chain A, domain 3) in NADPH--cytochrome P450 reductase in PDB 1amo.
SCOP SCOP annotations
52365
Class: Alpha and beta proteins (a/b)
Fold: Ferredoxin reductase-like, C-terminal NADP-linked domain
Superfamily: Ferredoxin reductase-like, C-terminal NADP-linked domain
Occurring in:
  1. NADPH--cytochrome P450 reductase
1 copy of SCOP domain 52365 (NADPH-cytochrome p450 reductase-like) in NADPH--cytochrome P450 reductase in PDB 1amo.
50438
Class: All beta proteins
Fold: Reductase/isomerase/elongation factor common domain
Superfamily: Riboflavin synthase domain-like
Occurring in:
  1. NADPH--cytochrome P450 reductase
1 copy of SCOP domain 50438 (NADPH-cytochrome p450 reductase FAD-binding domain-like) in NADPH--cytochrome P450 reductase in PDB 1amo.
52231
Class: Alpha and beta proteins (a/b)
Fold: Flavodoxin-like
Superfamily: Flavoproteins
Occurring in:
  1. NADPH--cytochrome P450 reductase
1 copy of SCOP domain 52231 (Cytochrome p450 reductase N-terminal domain-like) in NADPH--cytochrome P450 reductase in PDB 1amo.