• 1
    Masters BS, Kamin H, Gibson QH & Williams CH Jr (1965) Studies on the mechanism of microsomal triphosphopyridine nucleotide–cytochrome c reductase. J Biol Chem 240, 921931.
  • 2
    Iyanagi T & Mason HS (1973) Some properties of hepatic reduced nicotinamide adenine dinucleotide phosphate–cytochrome c reductase. Biochemistry 12, 22972308.
  • 3
    Leclerc D, Wilson A, Dumas R, Gafuik C, Song D, Watkins D, Heng HH, Rommens JM, Scherer SW, Rosenblatt DS et al. (1998) Cloning and mapping of a cDNA for methionine synthase reductase, a flavoprotein defective in patients with homocystinuria. Proc Natl Acad Sci USA 95, 30593064.
  • 4
    Olteanu H & Banerjee R (2001) Human methionine synthase reductase, a soluble P-450 reductase-like dual flavoprotein, is sufficient for NADPH-dependent methionine synthase activation. J Biol Chem 276, 3555835563.
  • 5
    Vermilion JL & Coon MJ (1978) Identification of the high and low potential flavins of liver microsomal NADPH–cytochrome P-450 reductase. J Biol Chem 253, 88128819.
  • 6
    Iyanagi T, Xia C & Kim JJ (2012) NADPH–cytochrome P450 oxidoreductase: prototypic member of the diflavin reductase family. Arch Biochem Biophys 528, 7289.
  • 7
    Enoch HG, Fleming PJ & Strittmatter P (1979) The binding of cytochrome b5 to phospholipid vesicles and biological membranes. Effect of orientation on intermembrane transfer and digestion by carboxypeptidase Y. J Biol Chem 254, 64836488.
  • 8
    Schacter BA, Meyer UA & Marver HS (1972) Hemoprotein catabolism during stimulation of microsomal lipid peroxidation. Biochim Biophys Acta 279, 221227.
  • 9
    Ilan Z, Ilan R & Cinti DL (1981) Evidence for a new physiological role of hepatic NADPH:ferricytochrome (P-450) oxidoreductase. Direct electron input to the microsomal fatty acid chain elongation system. J Biol Chem 256, 1006610072.
  • 10
    Banerjee RV & Matthews RG (1990) Cobalamin-dependent methionine synthase. FASEB J 4, 14501459.
  • 11
    Porter TD & Kasper CB (1986) NADPH–cytochrome P-450 oxidoreductase: flavin mononucleotide and flavin adenine dinucleotide domains evolved from different flavoproteins. Biochemistry 25, 16821687.
  • 12
    Wang M, Roberts DL, Paschke R, Shea TM, Masters BS & Kim JJ (1997) Three-dimensional structure of NADPH–cytochrome P450 reductase: prototype for FMN- and FAD-containing enzymes. Proc Natl Acad Sci USA 94, 84118416.
  • 13
    Vincent B, Morellet N, Fatemi F, Aigrain L, Truan G, Guittet E & Lescop E (2012) The closed and compact domain organization of the 70-kDa human cytochrome P450 reductase in its oxidized state as revealed by NMR. J Mol Biol 420, 296309.
  • 14
    Hamdane D, Xia C, Im SC, Zhang H, Kim JJ & Waskell L (2009) Structure and function of an NADPH–cytochrome P450 oxidoreductase in an open conformation capable of reducing cytochrome P450. J Biol Chem 284, 1137411384.
  • 15
    Ellis J, Gutierrez A, Barsukov IL, Huang WC, Grossmann JG & Roberts GC (2009) Domain motion in cytochrome P450 reductase: conformational equilibria revealed by NMR and small-angle X-ray scattering. J Biol Chem 284, 3662836637.
  • 16
    Jenner M, Ellis J, Huang WC, Lloyd Raven E, Roberts GC & Oldham NJ (2011) Detection of a protein conformational equilibrium by electrospray ionisation-ion mobility-mass spectrometry. Angew Chem Int Ed Engl 50, 82918294.
  • 17
    Xia C, Hamdane D, Shen AL, Choi V, Kasper CB, Pearl NM, Zhang H, Im SC, Waskell L & Kim JJ (2011) Conformational changes of NADPH–cytochrome P450 oxidoreductase are essential for catalysis and cofactor binding. J Biol Chem 286, 1624616260.
  • 18
    Deng Z, Aliverti A, Zanetti G, Arakaki AK, Ottado J, Orellano EG, Calcaterra NB, Ceccarelli EA, Carrillo N & Karplus PA (1999) A productive NADP+ binding mode of ferredoxin–NADP+ reductase revealed by protein engineering and crystallographic studies. Nat Struct Biol 6, 847853.
  • 19
    Hubbard PA, Shen AL, Paschke R, Kasper CB & Kim JJ (2001) NADPH–cytochrome P450 oxidoreductase. Structural basis for hydride and electron transfer. J Biol Chem 276, 2916329170.
  • 20
    Meints CE, Gustafsson FS, Scrutton NS & Wolthers KR (2011) Tryptophan 697 modulates hydride and interflavin electron transfer in human methionine synthase reductase. Biochemistry 50, 1113111142.
  • 21
    Gutierrez A, Doehr O, Paine M, Wolf CR, Scrutton NS & Roberts GC (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, 1599015999.
  • 22
    Wolthers KR, Lou XD, Toogood HS, Leys D & Scrutton NS (2007) Mechanism of coenzyme binding to human methionine synthase reductase revealed through the crystal structure of the FNR-like module and isothermal titration calorimetry. Biochemistry 46, 1183311844.
  • 23
    Grunau A, Paine MJ, Ladbury JE & Gutierrez A (2006) Global effects of the energetics of coenzyme binding: NADPH controls the protein interaction properties of human cytochrome P450 reductase. Biochemistry 45, 14211434.
  • 24
    Murataliev MB & Feyereisen R (2000) Interaction of NADP(H) with oxidized and reduced P450 reductase during catalysis. Studies with nucleotide analogues. Biochemistry 39, 50665074.
  • 25
    Oprian DD & Coon MJ (1982) Oxidation–reduction states of FMN and FAD in NADPH–cytochrome P-450 reductase during reduction by NADPH. J Biol Chem 257, 89358944.
  • 26
    Gutierrez A, Lian LY, Wolf CR, Scrutton NS & Roberts GC (2001) Stopped-flow kinetic studies of flavin reduction in human cytochrome P450 reductase and its component domains. Biochemistry 40, 19641975.
  • 27
    Brenner S, Hay S, Munro AW & Scrutton NS (2008) Inter-flavin electron transfer in cytochrome P450 reductase – effects of solvent and pH identify hidden complexity in mechanism. FEBS J 275, 45404557.
  • 28
    Munro AW, Noble MA, Robledo L, Daff SN & Chapman SK (2001) Determination of the redox properties of human NADPH–cytochrome P450 reductase. Biochemistry 40, 19561963.
  • 29
    Wolthers KR & Scrutton NS (2004) Electron transfer in human methionine synthase reductase studied by stopped-flow spectrophotometry. Biochemistry 43, 490500.
  • 30
    Dohr O, Paine MJ, Friedberg T, Roberts GC & Wolf CR (2001) Engineering of a functional human NADH-dependent cytochrome P450 system. Proc Natl Acad Sci USA 98, 8186.
  • 31
    Neeli R, Girvan HM, Lawrence A, Warren MJ, Leys D, Scrutton NS & Munro AW (2005) The dimeric form of flavocytochrome P450 BM3 is catalytically functional as a fatty acid hydroxylase. FEBS Lett 579, 55825588.
  • 32
    Konas DW, Zhu K, Sharma M, Aulak KS, Brudvig GW & Stuehr DJ (2004) The FAD-shielding residue Phe1395 regulates neuronal nitric-oxide synthase catalysis by controlling NADP+ affinity and a conformational equilibrium within the flavoprotein domain. J Biol Chem 279, 3541235425.
  • 33
    Murataliev MB, Feyereisen R & Walker FA (2004) Electron transfer by diflavin reductases. Biochim Biophys Acta 1698, 126.
  • 34
    Nogues I, Tejero J, Hurley JK, Paladini D, Frago S, Tollin G, Mayhew SG, Gomez-Moreno C, Ceccarelli EA, Carrillo N et al. (2004) Role of the C-terminal tyrosine of ferredoxin–nicotinamide adenine dinucleotide phosphate reductase in the electron transfer processes with its protein partners ferredoxin and flavodoxin. Biochemistry 43, 61276137.
  • 35
    Lostao A, Gomez-Moreno C, Mayhew SG & Sancho J (1997) Differential stabilization of the three FMN redox forms by tyrosine 94 and tryptophan 57 in flavodoxin from Anabaena and its influence on the redox potentials. Biochemistry 36, 1433414344.
  • 36
    Neeli R, Roitel O, Scrutton NS & Munro AW (2005) Switching pyridine nucleotide specificity in P450 BM3: mechanistic analysis of the W1046H and W1046A enzymes. J Biol Chem 280, 1763417644.
  • 37
    Stubbe J, Nocera DG, Yee CS & Chang MC (2003) Radical initiation in the class I ribonucleotide reductase: long-range proton-coupled electron transfer? Chem Rev 103, 21672201.
  • 38
    Iyanagi T, Makino N & Mason HS (1974) Redox properties of the reduced nicotinamide adenine dinucleotide phosphate–cytochrome P-450 and reduced nicotinamide adenine dinucleotide–cytochrome b5 reductases. Biochemistry 13, 17011710.
  • 39
    Viola RE, Cook PF & Cleland WW (1979) Stereoselective preparation of deuterated reduced nicotinamide adenine nucleotides and substrates by enzymatic synthesis. Anal Biochem 96, 334340.
  • 40
    Wolthers KR, Basran J, Munro AW & Scrutton NS (2003) Molecular dissection of human methionine synthase reductase: determination of the flavin redox potentials in full-length enzyme and isolated flavin-binding domains. Biochemistry 42, 39113920.
  • 41
    Dutton PL (1978) Redox potentiometry: determination of midpoint potentials of oxidation–reduction components of biological electron-transfer systems. Methods Enzymol 54, 411435.
  • 42
    Daff SN, Chapman SK, Turner KL, Holt RA, Govindaraj S, Poulos TL & Munro AW (1997) Redox control of the catalytic cycle of flavocytochrome P-450 BM3. Biochemistry 36, 1381613823.