PDBsum entry 1amo

Go to PDB code: 
protein ligands Protein-protein interface(s) links
Oxidoreductase PDB id
Protein chains
601 a.a. *
FAD ×2
FMN ×2
NAP ×2
Waters ×156
* Residue conservation analysis
PDB id:
Name: Oxidoreductase
Title: Three-dimensional structure of NADPH-cytochrome p450 reductase: prototype for fmn-and fad-containing enzymes
Structure: NADPH-cytochrome p450 reductase. Chain: a, b. Fragment: hydrophilic domain. Synonym: cpr, p450r. Engineered: yes
Source: Rattus norvegicus. Norway rat. Organism_taxid: 10116. Organ: liver. Cellular_location: mitochondria. Expressed in: escherichia coli. Expression_system_taxid: 562
2.60Å     R-factor:   0.200     R-free:   0.310
Authors: M.Wang,D.L.Roberts,R.Paschke,T.M.Shea,B.S.S.Masters, J.J.P.Kim
Key ref:
M.Wang et al. (1997). Three-dimensional structure of NADPH-cytochrome P450 reductase: prototype for FMN- and FAD-containing enzymes. Proc Natl Acad Sci U S A, 94, 8411-8416. PubMed id: 9237990 DOI: 10.1073/pnas.94.16.8411
17-Jun-97     Release date:   17-Jun-98    
Go to PROCHECK summary

Protein chains
Pfam   ArchSchema ?
P00388  (NCPR_RAT) -  NADPH--cytochrome P450 reductase
678 a.a.
601 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.  - NADPH--hemoprotein reductase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: NADPH + n oxidized hemoprotein = NADP+ + n reduced hemoprotein
+ n oxidized hemoprotein
= NADP(+)
+ n reduced hemoprotein
      Cofactor: FAD; FMN
Bound ligand (Het Group name = FAD) corresponds exactly
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     membrane   6 terms 
  Biological process     regulation of growth plate cartilage chondrocyte proliferation   24 terms 
  Biochemical function     electron carrier activity     13 terms  


DOI no: 10.1073/pnas.94.16.8411 Proc Natl Acad Sci U S A 94:8411-8416 (1997)
PubMed id: 9237990  
Three-dimensional structure of NADPH-cytochrome P450 reductase: prototype for FMN- and FAD-containing enzymes.
M.Wang, D.L.Roberts, R.Paschke, T.M.Shea, B.S.Masters, J.J.Kim.
Microsomal NADPH-cytochrome P450 reductase (CPR) is one of only two mammalian enzymes known to contain both FAD and FMN, the other being nitric-oxide synthase. CPR is a membrane-bound protein and catalyzes electron transfer from NADPH to all known microsomal cytochromes P450. The structure of rat liver CPR, expressed in Escherichia coli and solubilized by limited trypsinolysis, has been determined by x-ray crystallography at 2.6 A resolution. The molecule is composed of four structural domains: (from the N- to C- termini) the FMN-binding domain, the connecting domain, and the FAD- and NADPH-binding domains. The FMN-binding domain is similar to the structure of flavodoxin, whereas the two C-terminal dinucleotide-binding domains are similar to those of ferredoxin-NADP+ reductase (FNR). The connecting domain, situated between the FMN-binding and FNR-like domains, is responsible for the relative orientation of the other domains, ensuring the proper alignment of the two flavins necessary for efficient electron transfer. The two flavin isoalloxazine rings are juxtaposed, with the closest distance between them being about 4 A. The bowl-shaped surface near the FMN-binding site is likely the docking site of cytochrome c and the physiological redox partners, including cytochromes P450 and b5 and heme oxygenase.
  Selected figure(s)  
Figure 1.
Fig. 1. Stereoview of the electron density in the vicinity of the FAD and FMN of CPR. The 3|F[o]| 2|F[c]| electron density map computed^ with 2.6 Å resolution data is contoured at 1.2 level. Residues within close contact of the flavin ring are labeled. Four aromatic^ residues sandwich the flavin rings: Y178 and Y140 for FMN and^ Y456 and W677 for FAD.
Figure 4.
Fig. 4. Stereoview of the cofactor arrangement in CPR and multiple conformers for the bound NADP+. Electrons flow from NADPH to FAD and then to FMN. The FMN and^ FAD are represented by ball-and-stick, with the xylene portions of the isoalloxazine rings oriented toward each other. The adenine^ portion of NADP+ binds in a single conformation (ball-and-stick) while the nicotinamide^ (stick only) binds in multiple conformations. By rotation about the P[N]---O---P[A] bond, the nicotinamide ring could displace W677 at the re-side of the FAD ring, placing it in the optimum orientation for hydride transfer from the NADPH to the N5 position of the^ FAD cofactor.
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20857167 D.Degregorio, S.J.Sadeghi, G.Di Nardo, G.Gilardi, and S.P.Solinas (2011).
Understanding uncoupling in the multiredox centre P450 3A4-BMR model system.
  J Biol Inorg Chem, 16, 109-116.  
21265736 L.Aigrain, D.Pompon, and G.Truan (2011).
Role of the interface between the FMN and FAD domains in the control of redox potential and electronic transfer of NADPH-cytochrome P450 reductase.
  Biochem J, 435, 197-206.  
21472912 S.E.Rigby, X.Lou, H.S.Toogood, K.R.Wolthers, and N.S.Scrutton (2011).
ELDOR Spectroscopy Reveals that Energy Landscapes in Human Methionine Synthase Reductase are Extensively Remodelled Following Ligand and Partner Protein Binding.
  Chembiochem, 12, 863-867.  
21084761 Y.Saito, N.Yamamoto, N.Katori, K.Maekawa, H.Fukushima-Uesaka, D.Sugimoto, K.Kurose, K.Sai, N.Kaniwa, J.Sawada, H.Kunitoh, Y.Ohe, T.Yoshida, Y.Matsumura, N.Saijo, H.Okuda, and T.Tamura (2011).
Genetic polymorphisms and haplotypes of por, encoding cytochrome p450 oxidoreductase, in a Japanese population.
  Drug Metab Pharmacokinet, 26, 107-116.  
20718865 A.Welland, and S.Daff (2010).
Conformation-dependent hydride transfer in neuronal nitric oxide synthase reductase domain.
  FEBS J, 277, 3833-3843.  
19884324 C.C.Marohnic, S.P.Panda, K.McCammon, J.Rueff, B.S.Masters, and M.Kranendonk (2010).
Human cytochrome P450 oxidoreductase deficiency caused by the Y181D mutation: molecular consequences and rescue of defect.
  Drug Metab Dispos, 38, 332-340.  
20940534 D.Sandee, K.Morrissey, V.Agrawal, H.K.Tam, M.A.Kramer, T.S.Tracy, K.M.Giacomini, and W.L.Miller (2010).
Effects of genetic variants of human P450 oxidoreductase on catalysis by CYP2D6 in vitro.
  Pharmacogenet Genomics, 20, 677-686.  
20071338 J.R.Reed, M.Eyer, and W.L.Backes (2010).
Functional interactions between cytochromes P450 1A2 and 2B4 require both enzymes to reside in the same phospholipid vesicle: evidence for physical complex formation.
  J Biol Chem, 285, 8942-8952.  
20406405 J.Varadarajan, J.Guilleminot, C.Saint-Jore-Dupas, B.Piégu, M.E.Chabouté, V.Gomord, R.C.Coolbaugh, M.Devic, and V.Delorme (2010).
ATR3 encodes a diflavin reductase essential for Arabidopsis embryo development.
  New Phytol, 187, 67-82.  
20697309 V.Agrawal, J.H.Choi, K.M.Giacomini, and W.L.Miller (2010).
Substrate-specific modulation of CYP3A4 activity by genetic variants of cytochrome P450 oxidoreductase.
  Pharmacogenet Genomics, 20, 611-618.  
20879989 Y.Farooq, and G.C.Roberts (2010).
Kinetics of electron transfer between NADPH-cytochrome P450 reductase and cytochrome P450 3A4.
  Biochem J, 432, 485-493.  
19944754 Y.Hong, H.Li, Y.C.Yuan, and S.Chen (2010).
Sequence-function correlation of aromatase and its interaction with reductase.
  J Steroid Biochem Mol Biol, 118, 203-206.  
18977373 A.A.Brimfield, A.M.Mancebo, R.P.Mason, J.J.Jiang, A.G.Siraki, and M.J.Novak (2009).
Free radical production from the interaction of 2-chloroethyl vesicants (mustard gas) with pyridine nucleotide-driven flavoprotein electron transport systems.
  Toxicol Appl Pharmacol, 234, 128-134.  
19908820 A.Das, and S.G.Sligar (2009).
Modulation of the cytochrome P450 reductase redox potential by the phospholipid bilayer.
  Biochemistry, 48, 12104-12112.  
19374516 A.M.Gomes, S.Winter, K.Klein, M.Turpeinen, E.Schaeffeler, M.Schwab, and U.M.Zanger (2009).
Pharmacogenomics of human liver cytochrome P450 oxidoreductase: multifactorial analysis and impact on microsomal drug oxidation.
  Pharmacogenomics, 10, 579-599.  
19398561 B.S.Masters, and B.S.Masters (2009).
A professional and personal odyssey.
  J Biol Chem, 284, 19765-19780.  
19690675 C.Feng, and G.Tollin (2009).
Regulation of interdomain electron transfer in the NOS output state for NO production.
  Dalton Trans, (), 6692-6700.  
19737939 C.Xia, I.Misra, T.Iyanagi, and J.J.Kim (2009).
Regulation of interdomain interactions by calmodulin in inducible nitric-oxide synthase.
  J Biol Chem, 284, 30708-30717.  
18982412 D.Eberle, P.Ullmann, D.Werck-Reichhart, and M.Petersen (2009).
cDNA cloning and functional characterisation of CYP98A14 and NADPH:cytochrome P450 reductase from Coleus blumei involved in rosmarinic acid biosynthesis.
  Plant Mol Biol, 69, 239-253.  
19225657 D.J.Heyes, A.M.Quinn, P.M.Cullis, M.Lee, A.W.Munro, and N.S.Scrutton (2009).
Internal electron transfer in multi-site redox enzymes is accessed by laser excitation of thiouredopyrene-3,6,8-trisulfonate (TUPS).
  Chem Commun (Camb), (), 1124-1126.  
19583767 D.J.Stuehr, J.Tejero, and M.M.Haque (2009).
Structural and mechanistic aspects of flavoproteins: electron transfer through the nitric oxide synthase flavoprotein domain.
  FEBS J, 276, 3959-3974.  
19858215 J.Ellis, A.Gutierrez, I.L.Barsukov, W.C.Huang, J.G.Grossmann, and G.C.Roberts (2009).
Domain motion in cytochrome P450 reductase: conformational equilibria revealed by NMR and small-angle x-ray scattering.
  J Biol Chem, 284, 36628-36637.  
19243433 K.R.Wolthers, and N.S.Scrutton (2009).
Cobalamin uptake and reactivation occurs through specific protein interactions in the methionine synthase-methionine synthase reductase complex.
  FEBS J, 276, 1942-1951.  
  19255466 L.Aigrain, D.Pompon, G.Truan, and S.Moréra (2009).
Cloning, purification, crystallization and preliminary X-ray analysis of a chimeric NADPH-cytochrome P450 reductase.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 65, 210-212.  
19483672 L.Aigrain, D.Pompon, S.Moréra, and G.Truan (2009).
Structure of the open conformation of a functional chimeric NADPH cytochrome P450 reductase.
  EMBO Rep, 10, 742-747.
PDB code: 3fjo
19432415 M.Kasim, H.C.Chen, and R.P.Swenson (2009).
Functional characterization of the re-face loop spanning residues 536-541 and its interactions with the cofactor in the flavin mononucleotide-binding domain of flavocytochrome P450 from Bacillus megaterium.
  Biochemistry, 48, 5131-5141.  
19583765 M.Medina (2009).
Structural and mechanistic aspects of flavoproteins: photosynthetic electron transfer from photosystem I to NADP+.
  FEBS J, 276, 3942-3958.  
19161969 N.Mast, W.L.Liao, I.A.Pikuleva, and I.V.Turko (2009).
Combined use of mass spectrometry and heterologous expression for identification of membrane-interacting peptides in cytochrome P450 46A1 and NADPH-cytochrome P450 oxidoreductase.
  Arch Biochem Biophys, 483, 81-89.  
19290671 R.P.Ilagan, J.Tejero, K.S.Aulak, S.S.Ray, C.Hemann, Z.Q.Wang, M.Gangoda, J.L.Zweier, and D.J.Stuehr (2009).
Regulation of FMN subdomain interactions and function in neuronal nitric oxide synthase.
  Biochemistry, 48, 3864-3876.  
19805543 S.Praporski, S.M.Ng, A.D.Nguyen, C.J.Corbin, A.Mechler, J.Zheng, A.J.Conley, and L.L.Martin (2009).
Organization of cytochrome P450 enzymes involved in sex steroid synthesis: PROTEIN-PROTEIN INTERACTIONS IN LIPID MEMBRANES.
  J Biol Chem, 284, 33224-33232.  
18821018 W.L.Miller (2009).
Androgen synthesis in adrenarche.
  Rev Endocr Metab Disord, 10, 3.  
19956630 Y.Hong, H.Li, J.Ye, Y.Miki, Y.C.Yuan, H.Sasano, D.B.Evans, and S.Chen (2009).
Epitope characterization of an aromatase monoclonal antibody suitable for the assessment of intratumoral aromatase activity.
  PLoS One, 4, e8050.  
19250198 Y.Hong, H.Li, Y.C.Yuan, and S.Chen (2009).
Molecular characterization of aromatase.
  Ann N Y Acad Sci, 1155, 112-120.  
18980384 C.G.Gherasim, U.Zaman, A.Raza, and R.Banerjee (2008).
Impeded electron transfer from a pathogenic FMN domain mutant of methionine synthase reductase and its responsiveness to flavin supplementation.
  Biochemistry, 47, 12515-12522.  
18218133 D.C.Gonzalez-Kristeller, L.Farage, L.C.Fiorini, W.F.Loomis, and A.M.da Silva (2008).
The P450 oxidoreductase, RedA, controls development beyond the mound stage in Dictyostelium discoideum.
  BMC Dev Biol, 8, 8.  
18852262 H.Li, A.Das, H.Sibhatu, J.Jamal, S.G.Sligar, and T.L.Poulos (2008).
Exploring the electron transfer properties of neuronal nitric-oxide synthase by reversal of the FMN redox potential.
  J Biol Chem, 283, 34762-34772.  
18513324 H.Sumimoto (2008).
Structure, regulation and evolution of Nox-family NADPH oxidases that produce reactive oxygen species.
  FEBS J, 275, 3249-3277.  
18815130 J.Tejero, A.Biswas, Z.Q.Wang, R.C.Page, M.M.Haque, C.Hemann, J.L.Zweier, S.Misra, and D.J.Stuehr (2008).
Stabilization and characterization of a heme-oxy reaction intermediate in inducible nitric-oxide synthase.
  J Biol Chem, 283, 33498-33507.
PDB code: 3dwj
18279389 M.A.Musumeci, A.K.Arakaki, D.V.Rial, D.L.Catalano-Dupuy, and E.A.Ceccarelli (2008).
Modulation of the enzymatic efficiency of ferredoxin-NADP(H) reductase by the amino acid volume around the catalytic site.
  FEBS J, 275, 1350-1366.  
18260112 M.Medina, R.Abagyan, C.Gómez-Moreno, and J.Fernandez-Recio (2008).
Docking analysis of transient complexes: interaction of ferredoxin-NADP+ reductase with ferredoxin and flavodoxin.
  Proteins, 72, 848-862.  
18847185 M.P.Hay, K.O.Hicks, K.Pchalek, H.H.Lee, A.Blaser, F.B.Pruijn, R.F.Anderson, S.S.Shinde, W.R.Wilson, and W.A.Denny (2008).
Tricyclic [1,2,4]triazine 1,4-dioxides as hypoxia selective cytotoxins.
  J Med Chem, 51, 6853-6865.  
18230729 N.Huang, V.Agrawal, K.M.Giacomini, and W.L.Miller (2008).
Genetics of P450 oxidoreductase: sequence variation in 842 individuals of four ethnicities and activities of 15 missense mutations.
  Proc Natl Acad Sci U S A, 105, 1733-1738.  
18556005 R.Nicoli, M.Bartolini, S.Rudaz, V.Andrisano, and J.L.Veuthey (2008).
Development of immobilized enzyme reactors based on human recombinant cytochrome P450 enzymes for phase I drug metabolism studies.
  J Chromatogr A, 1206, 2.  
18216718 S.N.Hart, S.Wang, K.Nakamoto, C.Wesselman, Y.Li, and X.B.Zhong (2008).
Genetic polymorphisms in cytochrome P450 oxidoreductase influence microsomal P450-catalyzed drug metabolism.
  Pharmacogenet Genomics, 18, 11-24.  
18433346 S.N.Hart, and X.B.Zhong (2008).
P450 oxidoreductase: genetic polymorphisms and implications for drug metabolism and toxicity.
  Expert Opin Drug Metab Toxicol, 4, 439-452.  
18539133 S.Sarapusit, C.Xia, I.Misra, P.Rongnoparut, and J.J.Kim (2008).
NADPH-cytochrome P450 oxidoreductase from the mosquito Anopheles minimus: kinetic studies and the influence of Leu86 and Leu219 on cofactor binding and protein stability.
  Arch Biochem Biophys, 477, 53-59.  
18551037 V.Agrawal, N.Huang, and W.L.Miller (2008).
Pharmacogenetics of P450 oxidoreductase: effect of sequence variants on activities of CYP1A2 and CYP2C19.
  Pharmacogenet Genomics, 18, 569-576.  
18194664 Y.Higashimoto, M.Sugishima, H.Sato, H.Sakamoto, K.Fukuyama, G.Palmer, and M.Noguchi (2008).
Mass spectrometric identification of lysine residues of heme oxygenase-1 that are involved in its interaction with NADPH-cytochrome P450 reductase.
  Biochem Biophys Res Commun, 367, 852-858.  
17448174 B.S.Kim, S.Y.Kim, J.Park, W.Park, K.Y.Hwang, Y.J.Yoon, W.K.Oh, B.Y.Kim, and J.S.Ahn (2007).
Sequence-based screening for self-sufficient P450 monooxygenase from a metagenome library.
  J Appl Microbiol, 102, 1392-1400.  
17635179 C.E.Flück, C.Nicolo, and A.V.Pandey (2007).
Clinical, structural and functional implications of mutations and polymorphisms in human NADPH P450 oxidoreductase.
  Fundam Clin Pharmacol, 21, 399-410.  
17554763 C.Gherasim, D.S.Rosenblatt, and R.Banerjee (2007).
Polymorphic background of methionine synthase reductase modulates the phenotype of a disease-causing mutation.
  Hum Mutat, 28, 1028-1033.  
17598560 D.Kaewpa, S.Boonsuepsakul, and P.Rongnoparut (2007).
Functional expression of mosquito NADPH-cytochrome P450 reductase in Escherichia coli.
  J Econ Entomol, 100, 946-953.  
17174478 J.J.Perry, L.Fan, and J.A.Tainer (2007).
Developing master keys to brain pathology, cancer and aging from the structural biology of proteins controlling reactive oxygen species and DNA repair.
  Neuroscience, 145, 1280-1299.  
17288554 K.R.Wolthers, H.S.Toogood, T.A.Jowitt, K.R.Marshall, D.Leys, and N.S.Scrutton (2007).
Crystal structure and solution characterization of the activation domain of human methionine synthase.
  FEBS J, 274, 738-750.
PDB code: 2o2k
17534530 M.Unno, T.Matsui, and M.Ikeda-Saito (2007).
Structure and catalytic mechanism of heme oxygenase.
  Nat Prod Rep, 24, 553-570.  
17827787 S.N.Hart, Y.Li, K.Nakamoto, C.Wesselman, and X.B.Zhong (2007).
Novel SNPs in cytochrome P450 oxidoreductase.
  Drug Metab Pharmacokinet, 22, 322-326.  
17960482 W.Arlt (2007).
P450 oxidoreductase deficiency and Antley-Bixler syndrome.
  Rev Endocr Metab Disord, 8, 301-307.  
16915000 C.E.Flück, and W.L.Miller (2006).
P450 oxidoreductase deficiency: a new form of congenital adrenal hyperplasia.
  Curr Opin Pediatr, 18, 435-441.  
16407065 D.C.Lamb, Y.Kim, L.V.Yermalitskaya, V.N.Yermalitsky, G.I.Lepesheva, S.L.Kelly, M.R.Waterman, and L.M.Podust (2006).
A second FMN binding site in yeast NADPH-cytochrome P450 reductase suggests a mechanism of electron transfer by diflavin reductases.
  Structure, 14, 51-61.
PDB codes: 2bf4 2bn4
16900491 R.A.Brown, and D.A.Case (2006).
Second derivatives in generalized Born theory.
  J Comput Chem, 27, 1662-1675.  
16605249 R.Pejchal, E.Campbell, B.D.Guenther, B.W.Lennon, R.G.Matthews, and M.L.Ludwig (2006).
Structural perturbations in the Ala --> Val polymorphism of methylenetetrahydrofolate reductase: how binding of folates may protect against inactivation.
  Biochemistry, 45, 4808-4818.
PDB codes: 2fmn 2fmo
16234920 H.E.Seward, H.M.Girvan, and A.W.Munro (2005).
Cytochrome P450s: creating novel ligand sets.
  Dalton Trans, (), 3419-3426.  
16249336 M.Jáchymová, P.Martásek, S.Panda, L.J.Roman, M.Panda, T.M.Shea, Y.Ishimura, J.J.Kim, and B.S.Masters (2005).
Recruitment of governing elements for electron transfer in the nitric oxide synthase family.
  Proc Natl Acad Sci U S A, 102, 15833-15838.  
15832443 M.J.Coon (2005).
Cytochrome P450: nature's most versatile biological catalyst.
  Annu Rev Pharmacol Toxicol, 45, 1.  
15793702 N.Huang, A.V.Pandey, V.Agrawal, W.Reardon, P.D.Lapunzina, D.Mowat, E.W.Jabs, G.Van Vliet, J.Sack, C.E.Flück, and W.L.Miller (2005).
Diversity and function of mutations in p450 oxidoreductase in patients with Antley-Bixler syndrome and disordered steroidogenesis.
  Am J Hum Genet, 76, 729-749.  
15789405 T.Mayoral, M.Martínez-Júlvez, I.Pérez-Dorado, J.Sanz-Aparicio, C.Gómez-Moreno, M.Medina, and J.A.Hermoso (2005).
Structural analysis of interactions for complex formation between Ferredoxin-NADP+ reductase and its protein partners.
  Proteins, 59, 592-602.
PDB codes: 1e62 1e63 1e64 1go2 1qgy
16467261 W.L.Miller, N.Huang, A.V.Pandey, C.E.Flück, and V.Agrawal (2005).
P450 oxidoreductase deficiency: a new disorder of steroidogenesis.
  Ann N Y Acad Sci, 1061, 100-108.  
15182370 A.J.Dunford, K.R.Marshall, A.W.Munro, and N.S.Scrutton (2004).
Thermodynamic and kinetic analysis of the isolated FAD domain of rat neuronal nitric oxide synthase altered in the region of the FAD shielding residue Phe1395.
  Eur J Biochem, 271, 2548-2560.  
14758361 C.E.Flück, T.Tajima, A.V.Pandey, W.Arlt, K.Okuhara, C.F.Verge, E.W.Jabs, B.B.Mendonça, K.Fujieda, and W.L.Miller (2004).
Mutant P450 oxidoreductase causes disordered steroidogenesis with and without Antley-Bixler syndrome.
  Nat Genet, 36, 228-230.  
15264278 M.Adachi, K.Tachibana, Y.Asakura, T.Yamamoto, K.Hanaki, and A.Oka (2004).
Compound heterozygous mutations of cytochrome P450 oxidoreductase gene (POR) in two patients with Antley-Bixler syndrome.
  Am J Med Genet A, 128, 333-339.  
15009198 M.H.Hefti, K.J.Françoijs, Vries, R.Dixon, and J.Vervoort (2004).
The PAS fold. A redefinition of the PAS domain based upon structural prediction.
  Eur J Biochem, 271, 1198-1208.  
15560792 M.Sugishima, C.T.Migita, X.Zhang, T.Yoshida, and K.Fukuyama (2004).
Crystal structure of heme oxygenase-1 from cyanobacterium Synechocystis sp. PCC 6803 in complex with heme.
  Eur J Biochem, 271, 4517-4525.
PDB code: 1we1
14996812 S.J.Barkley, R.M.Cornish, and C.D.Poulter (2004).
Identification of an Archaeal type II isopentenyl diphosphate isomerase in methanothermobacter thermautotrophicus.
  J Bacteriol, 186, 1811-1817.  
15220035 W.Arlt, E.A.Walker, N.Draper, H.E.Ivison, J.P.Ride, F.Hammer, S.M.Chalder, M.Borucka-Mankiewicz, B.P.Hauffa, E.M.Malunowicz, P.M.Stewart, and C.H.Shackleton (2004).
Congenital adrenal hyperplasia caused by mutant P450 oxidoreductase and human androgen synthesis: analytical study.
  Lancet, 363, 2128-2135.  
15350602 W.L.Miller (2004).
P450 oxidoreductase deficiency: a new disorder of steroidogenesis with multiple clinical manifestations.
  Trends Endocrinol Metab, 15, 311-315.  
12787027 A.Gutierrez, A.W.Munro, A.Grunau, C.R.Wolf, N.S.Scrutton, and G.C.Roberts (2003).
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.  
14502987 L.Lamattina, C.García-Mata, M.Graziano, and G.Pagnussat (2003).
Nitric oxide: the versatility of an extensive signal molecule.
  Annu Rev Plant Biol, 54, 109-136.  
12709048 N.Carrillo, and E.A.Ceccarelli (2003).
Open questions in ferredoxin-NADP+ reductase catalytic mechanism.
  Eur J Biochem, 270, 1900-1915.  
12631275 R.D.Finn, J.Basran, O.Roitel, C.R.Wolf, A.W.Munro, M.J.Paine, and N.S.Scrutton (2003).
Determination of the redox potentials and electron transfer properties of the FAD- and FMN-binding domains of the human oxidoreductase NR1.
  Eur J Biochem, 270, 1164-1175.  
12076537 A.W.Munro, D.G.Leys, K.J.McLean, K.R.Marshall, T.W.Ost, S.Daff, C.S.Miles, S.K.Chapman, D.A.Lysek, C.C.Moser, C.C.Page, and P.L.Dutton (2002).
P450 BM3: the very model of a modern flavocytochrome.
  Trends Biochem Sci, 27, 250-257.  
11790835 J.Freigang, K.Diederichs, K.P.Schäfer, W.Welte, and R.Paul (2002).
Crystal structure of oxidized flavodoxin, an essential protein in Helicobacter pylori.
  Protein Sci, 11, 253-261.
PDB code: 1fue
12372607 J.T.Jarrett, and J.T.Wan (2002).
Thermal inactivation of reduced ferredoxin (flavodoxin):NADP+ oxidoreductase from Escherichia coli.
  FEBS Lett, 529, 237-242.  
11933021 M.Recanatini, A.Cavalli, and P.Valenti (2002).
Nonsteroidal aromatase inhibitors: recent advances.
  Med Res Rev, 22, 282-304.  
12419614 R.De Mot, and A.H.Parret (2002).
A novel class of self-sufficient cytochrome P450 monooxygenases in prokaryotes.
  Trends Microbiol, 10, 502-508.  
12359874 S.Adak, M.Sharma, A.L.Meade, and D.J.Stuehr (2002).
A conserved flavin-shielding residue regulates NO synthase electron transfer and nicotinamide coenzyme specificity.
  Proc Natl Acad Sci U S A, 99, 13516-13521.  
11997441 T.H.Bayburt, and S.G.Sligar (2002).
Single-molecule height measurements on microsomal cytochrome P450 in nanometer-scale phospholipid bilayer disks.
  Proc Natl Acad Sci U S A, 99, 6725-6730.  
11329263 A.Gutierrez, L.Y.Lian, C.R.Wolf, N.S.Scrutton, and G.C.Roberts (2001).
Stopped-flow kinetic studies of flavin reduction in human cytochrome P450 reductase and its component domains.
  Biochemistry, 40, 1964-1975.  
11329262 A.W.Munro, M.A.Noble, L.Robledo, S.N.Daff, and S.K.Chapman (2001).
Determination of the redox properties of human NADPH-cytochrome P450 reductase.
  Biochemistry, 40, 1956-1963.  
11493691 D.A.Hall, C.W.Vander Kooi, C.N.Stasik, S.Y.Stevens, E.R.Zuiderweg, and R.G.Matthews (2001).
Mapping the interactions between flavodoxin and its physiological partners flavodoxin reductase and cobalamin-dependent methionine synthase.
  Proc Natl Acad Sci U S A, 98, 9521-9526.  
11525168 H.J.Chiu, E.Johnson, I.Schröder, and D.C.Rees (2001).
Crystal structures of a novel ferric reductase from the hyperthermophilic archaeon Archaeoglobus fulgidus and its complex with NADP+.
  Structure, 9, 311-319.
PDB codes: 1i0r 1i0s
11350928 H.K.Anandatheerthavarada, G.Amuthan, G.Biswas, M.A.Robin, R.Murali, M.R.Waterman, and N.G.Avadhani (2001).
Evolutionarily divergent electron donor proteins interact with P450MT2 through the same helical domain but different contact points.
  EMBO J, 20, 2394-2403.  
11294640 K.R.Wolthers, and M.I.Schimerlik (2001).
Reaction of neuronal nitric-oxide synthase with 2,6-dichloroindolphenol and cytochrome c3+: influence of the electron acceptor and binding of Ca2+-activated calmodulin on the kinetic mechanism.
  Biochemistry, 40, 4722-4737.  
11136248 O.Döhr, M.J.Paine, T.Friedberg, G.C.Roberts, and C.R.Wolf (2001).
Engineering of a functional human NADH-dependent cytochrome P450 system.
  Proc Natl Acad Sci U S A, 98, 81-86.  
11514662 O.Dym, and D.Eisenberg (2001).
Sequence-structure analysis of FAD-containing proteins.
  Protein Sci, 10, 1712-1728.  
11123926 A.Gutierrez, O.Doehr, M.Paine, C.R.Wolf, N.S.Scrutton, and G.C.Roberts (2000).
Trp-676 facilitates nicotinamide coenzyme exchange in the reductive half-reaction of human cytochrome P450 reductase: properties of the soluble W676H and W676A mutant reductases.
  Biochemistry, 39, 15990-15999.  
11150615 C.S.Miles, T.W.Ost, M.A.Noble, A.W.Munro, and S.K.Chapman (2000).
Protein engineering of cytochromes P-450.
  Biochim Biophys Acta, 1543, 383-407.  
11106776 D.F.Lewis, and P.Hlavica (2000).
Interactions between redox partners in various cytochrome P450 systems: functional and structural aspects.
  Biochim Biophys Acta, 1460, 353-374.  
10998235 G.A.Ziegler, and G.E.Schulz (2000).
Crystal structures of adrenodoxin reductase in complex with NADP+ and NADPH suggesting a mechanism for the electron transfer of an enzyme family.
  Biochemistry, 39, 10986-10995.
PDB codes: 1e1k 1e1l 1e1m 1e1n
10924903 H.Matsuda, S.Kimura, and T.Iyanagi (2000).
One-electron reduction of quinones by the neuronal nitric-oxide synthase reductase domain.
  Biochim Biophys Acta, 1459, 106-116.  
10677491 K.McMillan, M.Adler, D.S.Auld, J.J.Baldwin, E.Blasko, L.J.Browne, D.Chelsky, D.Davey, R.E.Dolle, K.A.Eagen, S.Erickson, R.I.Feldman, C.B.Glaser, C.Mallari, M.M.Morrissey, M.H.Ohlmeyer, G.Pan, J.F.Parkinson, G.B.Phillips, M.A.Polokoff, N.H.Sigal, R.Vergona, M.Whitlow, T.A.Young, and J.J.Devlin (2000).
Allosteric inhibitors of inducible nitric oxide synthase dimerization discovered via combinatorial chemistry.
  Proc Natl Acad Sci U S A, 97, 1506-1511.
PDB code: 1dd7
10819972 M.B.Murataliev, and R.Feyereisen (2000).
Interaction of NADP(H) with oxidized and reduced P450 reductase during catalysis. Studies with nucleotide analogues.
  Biochemistry, 39, 5066-5074.  
11082204 N.Horike, H.Takemori, Y.Nonaka, H.Sonobe, and M.Okamoto (2000).
Molecular cloning of NADPH-cytochrome P450 oxidoreductase from silkworm eggs. Its involvement in 20-hydroxyecdysone biosynthesis during embryonic development.
  Eur J Biochem, 267, 6914-6920.  
10678174 P.A.Williams, J.Cosme, V.Sridhar, E.F.Johnson, and D.E.McRee (2000).
Mammalian microsomal cytochrome P450 monooxygenase: structural adaptations for membrane binding and functional diversity.
  Mol Cell, 5, 121-131.
PDB code: 1dt6
10652125 A.Espinosa-Ruiz, J.M.Bellés, R.Serrano, and F.A.Culiáñez-MacIà (1999).
Arabidopsis thaliana AtHAL3: a flavoprotein related to salt and osmotic tolerance and plant growth.
  Plant J, 20, 529-539.  
10215853 A.Evrard, M.Zeghouf, M.Fontecave, C.Roby, and J.Covès (1999).
31P nuclear magnetic resonance study of the flavoprotein component of the Escherichia coli sulfite reductase.
  Eur J Biochem, 261, 430-437.  
10562539 B.R.Crane, R.J.Rosenfeld, A.S.Arvai, D.K.Ghosh, S.Ghosh, J.A.Tainer, D.J.Stuehr, and E.D.Getzoff (1999).
N-terminal domain swapping and metal ion binding in nitric oxide synthase dimerization.
  EMBO J, 18, 6271-6281.
PDB codes: 1df1 1qom
  10338023 D.J.Ayers, P.R.Gooley, A.Widmer-Cooper, and A.E.Torda (1999).
Enhanced protein fold recognition using secondary structure information from NMR.
  Protein Sci, 8, 1127-1133.  
10320659 D.J.Stuehr (1999).
Mammalian nitric oxide synthases.
  Biochim Biophys Acta, 1411, 217-230.  
10570242 H.Li, and T.L.Poulos (1999).
Fatty acid metabolism, conformational change, and electron transfer in cytochrome P-450(BM-3).
  Biochim Biophys Acta, 1441, 141-149.  
10594372 H.Matsuda, and T.Iyanagi (1999).
Calmodulin activates intramolecular electron transfer between the two flavins of neuronal nitric oxide synthase flavin domain.
  Biochim Biophys Acta, 1473, 345-355.  
10051560 I.F.Sevrioukova, H.Li, H.Zhang, J.A.Peterson, and T.L.Poulos (1999).
Structure of a cytochrome P450-redox partner electron-transfer complex.
  Proc Natl Acad Sci U S A, 96, 1863-1868.
PDB codes: 1bu7 1bvy
  10048323 Q.Zhao, S.Modi, G.Smith, M.Paine, P.D.McDonagh, C.R.Wolf, D.Tew, L.Y.Lian, G.C.Roberts, and H.P.Driessen (1999).
Crystal structure of the FMN-binding domain of human cytochrome P450 reductase at 1.93 A resolution.
  Protein Sci, 8, 298-306.
PDB code: 1b1c
15012211 W.H.Campbell (1999).
NITRATE REDUCTASE STRUCTURE, FUNCTION AND REGULATION: Bridging the Gap between Biochemistry and Physiology.
  Annu Rev Plant Physiol Plant Mol Biol, 50, 277-303.  
9461071 A.G.Murzin (1998).
Probable circular permutation in the flavin-binding domain.
  Nat Struct Biol, 5, 101.  
9875848 C.S.Raman, H.Li, P.Martásek, V.Král, B.S.Masters, and T.L.Poulos (1998).
Crystal structure of constitutive endothelial nitric oxide synthase: a paradigm for pterin function involving a novel metal center.
  Cell, 95, 939-950.
PDB codes: 1nse 2nse 3nse 4nse
9501215 D.Leclerc, A.Wilson, R.Dumas, C.Gafuik, D.Song, D.Watkins, H.H.Heng, J.M.Rommens, S.W.Scherer, D.S.Rosenblatt, and R.A.Gravel (1998).
Cloning and mapping of a cDNA for methionine synthase reductase, a flavoprotein defective in patients with homocystinuria.
  Proc Natl Acad Sci U S A, 95, 3059-3064.  
9667929 D.S.Bohle (1998).
Pathophysiological chemistry of nitric oxide and its oxygenation by-products.
  Curr Opin Chem Biol, 2, 194-200.  
9828361 F.Valetti, S.J.Sadeghi, Y.T.Meharenna, S.R.Leliveld, and G.Gilardi (1998).
Engineering multi-domain redox proteins containing flavodoxin as bio-transformer: preparatory studies by rational design.
  Biosens Bioelectron, 13, 675-685.  
  9865948 G.Sridhar Prasad, N.Kresge, A.B.Muhlberg, A.Shaw, Y.S.Jung, B.K.Burgess, and C.D.Stout (1998).
The crystal structure of NADPH:ferredoxin reductase from Azotobacter vinelandii.
  Protein Sci, 7, 2541-2549.
PDB code: 1a8p
9753700 J.A.Peterson, and S.E.Graham (1998).
A close family resemblance: the importance of structure in understanding cytochromes P450.
  Structure, 6, 1079-1085.  
9774150 J.J.McGuire, D.J.Anderson, B.J.McDonald, R.Narayanasami, and B.M.Bennett (1998).
Inhibition of NADPH-cytochrome P450 reductase and glyceryl trinitrate biotransformation by diphenyleneiodonium sulfate.
  Biochem Pharmacol, 56, 881-893.  
9860870 K.Brunner, A.Tortschanoff, B.Hemmens, P.J.Andrew, B.Mayer, and A.J.Kungl (1998).
Sensitivity of flavin fluorescence dynamics in neuronal nitric oxide synthase to cofactor-induced conformational changes and dimerization.
  Biochemistry, 37, 17545-17553.  
9843385 M.A.Noble, L.Quaroni, G.D.Chumanov, K.L.Turner, S.K.Chapman, R.P.Hanzlik, and A.W.Munro (1998).
Imidazolyl carboxylic acids as mechanistic probes of flavocytochrome P-450 BM3.
  Biochemistry, 37, 15799-15807.  
9558350 M.Zeghouf, M.Fontecave, D.Macherel, and J.Covès (1998).
The flavoprotein component of the Escherichia coli sulfite reductase: expression, purification, and spectral and catalytic properties of a monomeric form containing both the flavin adenine dinucleotide and the flavin mononucleotide cofactors.
  Biochemistry, 37, 6114-6123.  
9551547 T.L.Poulos, C.S.Raman, and H.Li (1998).
NO news is good news.
  Structure, 6, 255-258.  
9720224 T.Yamada, H.Imaishi, A.Oka, and H.Ohkawa (1998).
Molecular cloning and expression in Saccharomyces cerevisiae of tobacco NADPH-cytochrome P450 oxidoreductase cDNA.
  Biosci Biotechnol Biochem, 62, 1403-1411.  
9718311 V.Nivière, M.A.Vanoni, G.Zanetti, and M.Fontecave (1998).
Reaction of the NAD(P)H:flavin oxidoreductase from Escherichia coli with NADPH and riboflavin: identification of intermediates.
  Biochemistry, 37, 11879-11887.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.