Skip to main content
SpringerLink
Log in

NADPH Cytochrome P450 Reductase and Its Structural and Functional Domains

  • Chapter
Cytochrome P450

Abstract

NADPH cytochrome P450 reductase has been a topic of interest and study since Horecker1 first reported the isolation from pig liver after acetone extraction and trypsin treatment of a protein that catalyzed the reduction of cytochromes c. Since that initial report, much information has been revealed and reported about the nature, reactivities, structure, and regulation of the reductase that we have come to recognize as a component of the cytochrome P450-dependent drug metabolism system. The development of knowledge about the role and mechanism of NADPH cytochrome P450 reductase has been periodically discussed and reviewed.2–5 The most recent review (by Backes5) in 1993 focused on the function of cytochrome P450 reductase, summarizing and evaluating very elegantly a number of studies of the mechanism of electron transfer to the flavin centers of the reductase, interflavin electron transfer and transfer of electrons from the flavin centers to oxygen and/or the redox partners of cytochrome P450 reductase. This present review, therefore, will not cover mechanism in any more than a cursory fashion, but will attempt to focus on a summary of the salient features of the study of structural/functional regions or domains of cytochrome P450 reductase.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 229.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Horecker, B. L., 1950, Triphosphopyridine nucleotide-cytochrome c reductase in liver, J. Biol. Chem. 183: 593–605.

    CAS  Google Scholar 

  2. Strobel, H. W., Dignam, J. D., and Gum, J. R., 1980, NADPH cytochrome P450 reductase and its role in the mixed function oxidase reaction, Pharmacol. Ther. 8: 525–537.

    Article  PubMed  CAS  Google Scholar 

  3. Guengerich, F. P., 1987, Mammalian Cytochromes P450, Vols. 1 and 2, CRC Press, Boca Raton, FL.

    Google Scholar 

  4. Porter, T. D., and Coon, M. J., 1991, Cytochrome P450: Multiplicity of isoforms, substrates and catalytic and regulatory mechanisms, J. Biol. Chem. 266: 13469–13472.

    PubMed  CAS  Google Scholar 

  5. Backes, W. L., 1993, NADPH cytochrome P450 reductase: Function, in: Handbook of Experimental Pharmacology, Vol. 105, Cytochrome P450 ( J. B. Schenkman and H. Greim, eds.), Springer-Verlag, Berlin, pp. 15–34.

    Google Scholar 

  6. Lu, A. Y. H., and Coon, M. J., 1968, Role of hemoprotein P450 in fatty acid ta-hydroxylation in a soluble enzyme system from liver microsomes, J. Biol. Chem. 243: 1331–1332.

    PubMed  CAS  Google Scholar 

  7. Lu, A. Y. H., Junk, K. W., and Coon, M. J., 1969, Resolution of the cytochrome P450 containing to-hydroxylation system of liver microsomes into three components, J. Biol. Chem. 244: 3714–3721.

    PubMed  CAS  Google Scholar 

  8. Strobel, H. W., Lu, A. Y. H., Heidema, J., and Coon, M. J., 1970, Phosphatidylcholine requirement in the enzymatic reduction of hemoprotein P450 and in fatty acid, hydrocarbon and drug hydroxylation, J. Biol. Chem. 245: 4851–4854.

    PubMed  CAS  Google Scholar 

  9. Lu, A. Y. H., Strobel, H. W., and Coon, M. J., 1969, Hydroxylation of benzphetamine and other drugs by a solubilized form of cytochrome P450 from liver microsomes lipid: Requirement for drug demethylation, Biochem. Biophys. Res. Commun. 36: 545–551.

    Article  PubMed  CAS  Google Scholar 

  10. Lu, A. Y. H., Strobel, H. W., and Coon, M. J., 1970, Properties of a solubilized form of the cytochrome P450-containing mixed-function oxidase of liver microsomes, Mol. Pharmacol. 6: 213–220.

    PubMed  CAS  Google Scholar 

  11. Gillette, J. R., 1979, Effects of induction of cytochrome P450 enzymes on the concentrations of foreign compounds and their metabolites and on the toxicological effects of the compounds, Drug Metab. Rev. 10: 59–87.

    Article  PubMed  CAS  Google Scholar 

  12. Conney, A. H., 1982, Induction of microsomal enzymes by foreign compounds and carcinogenesis by polycyclic aromatic hydrocarbons, Cancer Res. 42: 4875–4917.

    PubMed  CAS  Google Scholar 

  13. Guengerich, F. P., 1977, Metabolism of vinyl chloride: Destruction of the heme of highly purified liver microsomal cytochrome P450 by a metabolite, Mol. Pharmacol. 13: 911–923.

    PubMed  CAS  Google Scholar 

  14. Stohs, S. J., Grafstrom, R. C., Burke, M. D., Moldeus, P. W., and Orrenius, S., 1976, The isolation of rat intestinal microsomes with stable cytochrome P450 and their metabolism of benzo[alpyrene, Arch. Biochem. Biophys. 177: 105–116.

    Article  PubMed  CAS  Google Scholar 

  15. Ellin, A., Jakobsson, S. B., Schenkman, J. B., and Orrenius, S., 1971, P450k of rat kidney cortex microsomes: Its involvement in fatty acid w-and (0)-1) hydroxylation, Arch. Biochem. Biophys. 150: 64–71.

    Article  Google Scholar 

  16. Fang, W. F., and Strobel, H. W., 1978, The drug and carcinogen metabolism system of rat colon microsomes, Arch. Biochem. Biophys. 186: 128–138.

    Article  PubMed  CAS  Google Scholar 

  17. Hodgson, A. V., White, T. B., White, J. W., and Strobel, H. W., 1993, Expression analysis of the mixed-function oxidase system in rat brain by the polymerase chain reaction, Mol. Cell. Biochem. 121: 171–174.

    Article  Google Scholar 

  18. Bergh, A. F., and Strobel, H. W., 1992, Reconstitution of the brain mixed-function oxidase system: Purification ofNADPH-cytochrome P450 reductase and partial purification of cytochrome P450 from whole rat brain, J. Neurochem. 59: 575–581.

    Article  PubMed  CAS  Google Scholar 

  19. Fennell, P. M., and Strobel, H. W., 1982, Preparation of homogeneous NADPH-cytochrome P450 reductase from rat hepatoma, Biochim. Biophys. Acta 709:173–177.

    Google Scholar 

  20. Oshinsky, R. J., and Strobel, H. W., 1987, Distribution and properties of cytochromes P450 and cytochrome P450 reductase from rat colon mucosal cells, int. J. Biochem. 19: 575–588.

    Article  PubMed  CAS  Google Scholar 

  21. Hammond, D. K., and Strobel, H. W., 1990, Human colon cell line LS 174T drug metabolizing system, Mol. Cell. Biochem. 93: 95–105.

    Article  PubMed  CAS  Google Scholar 

  22. White, T. B., Hammond, D. K., Vasquez, H., and Strobel, H. W., 1991, Expression of two cytochromes P450 involved in carcinogen activation in a human colon cell line, Mol. Cell. Biochem. 102: 61–69.

    Article  PubMed  CAS  Google Scholar 

  23. Nelson, D. R., Kamataki, T., Waxman, D. J., Guengerich, F. P., Estabrook, R. W., Feyereisen, R., Gonzales, F. J., Coon, M. J., Gunsalus, I. C., Gotoh, O., Okuda, K., and Nebert, D. W., 1993, The P450 superfamily: Update on new sequences, gene mapping, accession numbers, early trivial names and nomenclature, DNA Cell Biol. 12: 1–51.

    Article  PubMed  CAS  Google Scholar 

  24. Lu, A. Y. H., Kuntzman, R., West, S., Jacobson, M., and Conney, A. H., 1972, I. Reconstituted liver microsomal system that hydroxylates drugs, other foreign compounds, and endogenous substrates. II. Role of the cytochrome P450 and P448 fractions in drug and steroid hydroxylations, J. Biol. Chem. 247: 1724–1734.

    Google Scholar 

  25. van der Hoeven, T. A., Haugen, D. A., and Coon, M. J., 1974, Cytochrome P450 purified to apparent homogeneity from phenobarbital-induced rabbit liver microsomes: Catalytic activity and other properties, Biochem. Biophys. Res. Commun. 60: 569–575.

    Article  PubMed  Google Scholar 

  26. Levin, W., Ryan, D., West, S., and Lu, A. V. H., 1974, Preparation of partially purified, lipid-depleted cytochrome P450 and reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase from rat liver microsomes, J. Biol. Chem. 249: 1747–1754.

    PubMed  CAS  Google Scholar 

  27. Ryan, D., Lu, A. Y. H., West, S. B., and Levin, W., 1975, Multiple forms of cytochrome P450 in phenobarbital-and 3-methylcholanthrene-treated rats: Separation and spectral properties, J. Biol. Chem. 250: 2157–2163.

    PubMed  CAS  Google Scholar 

  28. Poulos, T. L., Finzel, B. C., Gunsalus, I. C., Wagner, G. C., and Kraut, J., 1985, The 2.6 A crystal structure of Pseudomonas putida cytochrome P450, J. Bio!. Chem. 260: 16122–16130.

    CAS  Google Scholar 

  29. Poulos, T. L., Finzel, B. C., and Howard, A. J., 1987, High resolution crystal structure of cytochrome P450cam, J. Mol. Biol. 195: 687–700.

    Article  PubMed  CAS  Google Scholar 

  30. Ravichandran, K. G., Boddupalli, S. S., Hasemann, C. A., Peterson, J. A., and Deisenhofer, J., 1993, Crystal structure of hemoprotein domain of P450 BM-3. A prototype for microsomal P450s, Science 261: 731–736.

    Article  PubMed  CAS  Google Scholar 

  31. Hasemann, C. A., Ravichandran, K. G., Peterson, J. A., and Deisenhofer, J., 1994, Crystal structure and refinement of cytochrome P450tep at 2.3 A resolution, J. Mol. Biol. 236: 1169–1185.

    Article  PubMed  CAS  Google Scholar 

  32. Dignam, J. D., and Strobel, H. W., 1975, Preparation of homogeneous NADPH cytochrome P450 reductase from rat liver, Biochem. Biophys. Res. Commun. 63: 845–852.

    Article  PubMed  CAS  Google Scholar 

  33. Iyanagi, T., and Mason, H. S., 1973, Some properties of hepatic reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase, Biochemistry 12: 2297–2308.

    Article  PubMed  CAS  Google Scholar 

  34. Iyanagi, T., Makino, N., and Mason, H. S., 1974, Redox properties of the reduced nicotinamide adenine dinucleotide phosphate-cytochrome P450 and reduced nicotinamide adenine dinucleotide-cytochrome b5 reductases, Biochemistry 13: 1701–1710.

    Article  PubMed  CAS  Google Scholar 

  35. Williams, C. H., and Kamin, H., 1962, Microsomal triphosphopyridine nucleotide cytochrome c reductase of liver, J. Bio!. Chem. 237: 587–595.

    CAS  Google Scholar 

  36. Phillips, A. H., and Langdon, R. G., 1962, Hepatic triphosphopyridine nucleotide cytochrome c reductase: Isolation, characterization and kinetic studies, J. Bio!. Chem. 237: 2652–2660.

    CAS  Google Scholar 

  37. Masters, B. S. S., Bilimoria, M. H., and Kamin, H., 1965, The mechanism of 1- and 2- electron transfers catalyzed by reduced triphosphopyridine nucleotide-cytochrome c reductase, J. Biol. Chem. 240: 4081–4088.

    PubMed  CAS  Google Scholar 

  38. Pederson, T. C., Buege, J. A., and Aust, S.D., 1973, Microsomal electron transport: The role of reduced nicotinamide adenine dinucleotide-phosphate-cytochrome c reductase in liver microsomal peroxidation, J. Biol. Chem. 248: 7134–7141.

    PubMed  CAS  Google Scholar 

  39. Yasukochi, Y., and Masters, B. S. S., 1976, Some properties of a detergent solubilized NADPH-cytochrome c (cytochrome P450) reductase purified by biospecific affinity chromatography, J. Biol. Chem. 251: 5337–5344.

    PubMed  CAS  Google Scholar 

  40. Dignam, J. D., and Strobel, H. W., 1977, NADPH-cytochrome P450 reductase from rat liver: Purification by affinity chromatography and characterization, Biochemistry 16: 1116–1123.

    Article  PubMed  CAS  Google Scholar 

  41. Knapp, J. A., Dignam, J. D., and Strobel, H. W., 1977, NADPH cytochrome P450 reductase: Circular dichroism and physical studies, J. Biol. Chem. 252: 437–443.

    PubMed  CAS  Google Scholar 

  42. Yasukochi, Y., Peterson, J. A., and Masters, B. S. S., 1979, NADPH cytochrome c (cytochrome P450) reductase: Spectrophotometric and stopped flow kinetic studies on the formation of reduced flavoprotein intermediates, J. Biol. Chem. 254: 7097–7104.

    PubMed  CAS  Google Scholar 

  43. Vermilion, J. L., and Coon, M. J., 1978, Identification of the high and low potential flavins of liver microsomal NADPH-cytochrome P450 reductase, J. Biol. Chem. 253: 8812–8819.

    PubMed  CAS  Google Scholar 

  44. Vermilion, J. L., and Coon, M. J., 1978, Purified liver microsomal NADPH-cytochrome P450 reductase: Spectral characterization of oxidation reduction states, J. Biol. Chem. 253: 2694–2704.

    PubMed  CAS  Google Scholar 

  45. Vermilion, J. L., Ballou, D. P., Massey, V., and Coon, M. J., 1981, Separate roles for FMN and FAD in catalysis by liver microsomal NADPH-cytochrome P450 reductase, J. Biol. Chem. 256: 266–277.

    PubMed  CAS  Google Scholar 

  46. Kurzban, G. P., and Strobel, H. W., 1986, Preparation and characterization of FAD-dependent NADPH cytochrome P450 reductase, J. Bio!. Chem. 261: 7824–7830.

    CAS  Google Scholar 

  47. Kurzban, G. P., and Strobel, H. W., 1986, Purification of flavin mononucleotide-dependent and flavin-adenine dinucleotide-dependent reduced nicotinamide-adenine dinucleotide phosphate-cytochrome P450 reductase by high-performance liquid chromatography on hydroxylapatite, J. Chromatogr. 358: 296–301.

    Article  PubMed  CAS  Google Scholar 

  48. Kurzban, G. P., Howarth, J., Palmer, G., and Strobel, H. W., 1990, NADPH-cytochrome P450 reductase: Physical properties and redox behavior in the absence of the FAD moiety, J. Biol. Chem. 265: 12272–12279.

    PubMed  CAS  Google Scholar 

  49. Narayanasami, R., Otvos, J. D., Kasper, C. B., Shen, A., Rajagopalan, J., McCabe, T. J., Okita, J. R., Hanahan, D. J., and Masters, B. S. S., 1992, 31P NMR spectroscopic studies on purified, native and cloned, expressed forms of NADPH-cytochrome P450 reductase, Biochemistry 31: 4210–4218.

    Google Scholar 

  50. Bastiaens, P. I. H., Bonants, P. J. M., Muller, F., and Visser, A. J. W. G., 1989, Time resolved fluorescence spectroscopy of NADPH cytochrome P450 reductase: Demonstration of energy transfer between the two prostethic groups, Biochemistry 28: 8416–8425.

    Article  PubMed  CAS  Google Scholar 

  51. Kuki, A., and Wolynes, P. G., 1987, Electron tunnelling paths in proteins, Science 236: 1642–1652.

    Article  Google Scholar 

  52. Centeno, F., and Gutierrez-Merino, C., 1992, Location of functional centers in the microsomal cytochrome P450 system, Biochemistry 31: 8473–8481.

    Article  PubMed  CAS  Google Scholar 

  53. Gum, J. R., and Strobel, H. W., 1979, Purified NADPH cytochrome P450 reductase: Interaction with hepatic microsomes and phospholipid vesicles, J. Biol. Chem. 254: 4177–4185.

    PubMed  CAS  Google Scholar 

  54. Gum, J. R., and Strobel, H. W., 1985, Isolation of the membrane-binding peptide of NADPH cytochrome P450 reductase: Characterization of the peptide and its role in the interaction of reductase with cytochrome P450, J. Biol. Chem. 256: 7478–7486.

    Google Scholar 

  55. Black, S. D., French, J. S., Williams, C. H., and Coon, M. J., 1979, Role of hydrophobic polypeptide in the N-terminal region of NADPH-cytochrome P450 reductase in complex formation with P450LM, Biochem. Biophys. Res. Commun. 91: 1528–1535.

    Article  PubMed  CAS  Google Scholar 

  56. Black, S. D., and Coon, M. J., 1982, Structural features of liver microsomal NADPH cytochrome P450 reductase: Hydrophobic domain, hydrophilic domain and connecting region, J. Biol. Chem. 257: 5929–5938.

    PubMed  CAS  Google Scholar 

  57. Haniu, M., Iyanagi, T., Miller, P., Lee, T. D., and Shively, J. E., 1986, Complete amino sequence of NADPH cytochrome P450 reductase from porcine hepatic microsomes, Biochemistry 25: 7906–7911.

    Article  PubMed  CAS  Google Scholar 

  58. Porter, T. D., Beck, T. W., and Kasper, C. B., 1990, NADPH cytochrome P450 oxidoreductase gene organization correlates with structural domains of the protein, Biochemistry 29: 9814–9818.

    Article  PubMed  CAS  Google Scholar 

  59. Traut, T. W., 1988, Do exons code for structural or functional units in proteins? Proc. Natl. Acad. Sci. USA 85: 2944–2948.

    Article  PubMed  CAS  Google Scholar 

  60. Tamburini, P. P., and Schenkman, J. B., 1986, Differences in the mechanism of functional interaction between NADPH cytochrome P450 reductase and its redox partners, Mol. Pharmacol. 30: 178–185.

    PubMed  CAS  Google Scholar 

  61. Nadler, S. G., and Strobel, H. W., 1988, Role of electrostatic interactions in the reaction of NADPH cytochrome P450 reductase with cytochromes P450, Arch. Biochem. Biophys. 261: 418–429.

    Article  PubMed  CAS  Google Scholar 

  62. Nadler, S. G., and Strobel, H. W., 1991, Identification and characterization of an NADPH-cytochrome P450 reductase-derived peptide involved in binding to cytochrome P450, Arch. Biochem. Biophys. 290: 277–284.

    Article  PubMed  CAS  Google Scholar 

  63. Nisimoto, Y., 1986, Localization of cytochrome c-binding domain on NADPH cytochrome P450 reductase, J. Biol. Chem. 261: 14232–14239.

    PubMed  CAS  Google Scholar 

  64. Tamburini, P. P., MacFarquhar, S., and Schenkman, J. B., 1986, Evidence of binary complex formation between cytochrome P450, cytochrome b5 and NADPH-cytochrome P450 reductase, Biochem. Biophys. Res. Commun. 134: 519–526.

    Article  PubMed  CAS  Google Scholar 

  65. Towbin, H., Stachelin, T., and Gordin, J., 1979, Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: Procedure and some applications, Proc. Natl. Acad. Sci. USA 76: 4350–4354.

    Article  PubMed  CAS  Google Scholar 

  66. Wada, F., Shibata, H., Goto, M., and Sakamoto, Y., 1968, Participation of the microsomal electron transport system involving cytochrome P450 in w-oxidation of fatty acids, Biochim. Biophys. Acta 162: 518–524.

    Article  PubMed  CAS  Google Scholar 

  67. Masters, B. S. S., Baron, J., Taylor, W. E., Isaacson, E. L., and LoSpalluto, J., 1971, Immunochemical studies on electron transport chains involving cytochrome P450, J. Biol. Chem. 246: 4143–4150.

    PubMed  CAS  Google Scholar 

  68. Shen, S., and Strobel, H. W., 1994, Probing the putative cytochrome P450- and cytochrome c-binding sites on NADPH cytochrome P450 reductase by antipeptide antibodies, Biochemistry 33: 8807–8812.

    Article  PubMed  CAS  Google Scholar 

  69. Porter, T. D., and Kasper, C. B., 1985, Coding nucleotide sequence of rat NADPH cytochrome P450 oxidoreductase cDNA and identification of flavin-binding domains, Proc. Natl. Acad. Sci. USA 82: 973–977.

    Article  PubMed  CAS  Google Scholar 

  70. Katagiri, M., Murakami, H., Yabusaki, Y., Sugigama, T., Okamoto, M., Yamano, T., and Ohkawa, H., 1986, Molecular cloning and sequence analyses of full-length cDNA for rabbit liver NADPH-cytochrome P450 reductase mRNA, J. Biochem. 100: 945–954.

    PubMed  CAS  Google Scholar 

  71. Shen, A. L., Porter, T. D., Wilson, T. E., and Kasper, C. B., 1989, Structural analysis of the FMN-binding domain of NADPH-cytochrome P450 oxidoreductase by site-directed mutagenesis, J. Biol. Chem. 264: 7584–7590.

    PubMed  CAS  Google Scholar 

  72. Hodgson, A. V., and Strobel, H. W., 1994, Polymerase chain reaction cloning, expression and purification of two FAD-binding domain fragments of cytochrome P450 reductase, FASEB J. 8: A1422.

    Google Scholar 

  73. Porter, J. D., and Kasper, C. B., 1985, NADPH-cytochrome P450 oxidoreductase: Flavin mononucleotide and flavin adenine dinucleotide domains evolved from different flavoproteins, Biochemistry 25: 1682–1687.

    Article  Google Scholar 

  74. Nisimoto, Y., and Shibata, Y., 1981, Location of functional -SH groups in NADPH cytochrome P450 reductase from rabbit liver microsomes, Biochim. Biophys. Acta 662: 291–299.

    Article  PubMed  CAS  Google Scholar 

  75. Lee, J. J., and Kaminsky, L. S., 1986, Fluorescence probing of the function-specific cysteines of rat microsomal NADPH-cytochrome P450 reductase, Biochem. Biophys. Res. Commun. 134: 393–399.

    Article  PubMed  CAS  Google Scholar 

  76. Nisimoto, Y., and Shibata, Y., 1982, Studies in FAD and FMN-binding domains in NADPH cytochrome P450 reductase from rabbit liver microsomes, J. Biol. Chem. 257: 12532–12539.

    PubMed  CAS  Google Scholar 

  77. Inano, H., Kurihara, S., and Tamaoki, B., 1988, Inactivation of rat testicular NADPH-cytochrome P450 reductase by 2,4,6-trinitrobenzene sulfonate, J. Steroid Biochem. 29: 227–232.

    Article  PubMed  CAS  Google Scholar 

  78. Inano, H., and Tamaoki, B., 1986, Chemical modification of NADPH-cytochrome P450 reductase: Presence of a lysine residue in the rat hepatic enzyme as the recognition site of the 2’ phosphate moiety of the cofactor, Eur. J. Biochem. 155: 485–489.

    Article  PubMed  CAS  Google Scholar 

  79. Strobel, H. W., Nadler, S. G., and Nelson, D. R., 1989, Cytochrome P450: Cytochrome P450 reductase interactions, Drug Metab. Rev. 20: 519–533.

    Article  PubMed  CAS  Google Scholar 

  80. Nisimoto, Y., Hayashi, R., Akutsu, H., Kyogoku, Y., and Shibata, Y., 1984, Photochemically induced dynamic nuclear polarization study on microsomal NADPH-cytochrome P450 reductase, J. Biol. Chem. 259: 2480–2483.

    PubMed  CAS  Google Scholar 

  81. Karplus, P. A., Daniels, M. K., and Herriott, J. R., 1991, Atomic structure of ferredoxin NADPH reductase: Prototype for a structurally novel family, Science 251: 60–66.

    Article  PubMed  CAS  Google Scholar 

  82. Karplus, P. A., and Schulz, G. E., 1987, Refined structure of glutathione reductase at 1.5 A resolution, J. Mol. Biol. 195: 701–729.

    Article  PubMed  CAS  Google Scholar 

  83. Karplus, P. A., and Schulz, G. E., 1989, Substrate binding and catalysis by glutathione reductase as derived from refined enzyme: Substrate crystal structures at 2 A resolution, J. Mol. Biol. 210: 163–180.

    Article  PubMed  CAS  Google Scholar 

  84. Bosterling, B., and Trudell, J. R., 1982, Association of cytochrome b5 and cytochrome P450 reductase with cytochrome P450 in the membrane and reconstituted vesicles, J. Biol. Chem. 257: 4783–4787.

    PubMed  CAS  Google Scholar 

  85. Voznesensky, A. I., and Schenkman, J. B., 1992, The cytochrome P450 2B4-NADPH cytochrome P450 reductase electron transfer complex is not formed by charge pairing, J. Biol. Chem. 267: 1466914676.

    Google Scholar 

  86. Voznesensky, A. I., and Schenkman, J. B., 1992, Inhibition of cytochrome P450 reductase by polyols has an electrostatic nature, Eur. J. Biochem. 210: 741–746.

    Article  PubMed  CAS  Google Scholar 

  87. Makower, A., Bernhardt, R., Rabe, H., Janig, G.-R., and Ruckpaul, K., 1984, Identification of lysine (384) in cytochrome P450LM2 as functionally-linked residue, Biomed. Biochim. Acta 43: 1333–1341.

    PubMed  CAS  Google Scholar 

  88. Bernhardt, R., Makower, A., Janig, G.-R., and Ruckpaul, K., 1984, Selective chemical modification of a functionally-linked lysine in cytochrome P450LM2, Biochim. Biophys. Acta 785: 186–190.

    Article  PubMed  CAS  Google Scholar 

  89. Nelson, D. R., and Strobel, H. W., 1988, On the membrane topology of vertebrate cytochrome P450 proteins, J. Biol. Chem. 263: 6038–6050.

    PubMed  CAS  Google Scholar 

  90. Nelson, D. R., and Strobel, H. W., 1989, Secondary structure prediction of 52 membrane-bound cytochromes P450 shows a strong structural similarity to P450cam, Biochemistry 28: 656–660.

    Article  PubMed  CAS  Google Scholar 

  91. Narhi, L. D., and Fulco, A. J., 1986, Characterization of a catalytically self-sufficient 119,000 dalton cytochrome P450 monooxygenase induced by barbiturates in Bacillus megaterium, J. Biol. Chem. 261: 7160–7169.

    PubMed  CAS  Google Scholar 

  92. Djordjevic, S., Wang, M., Shea, T., Roberts, D., Camitta, M., Masters, B. S. S., and Kim, J. J. P., 1994, Crystallization and preliminary x-ray studies of NADPH cytochrome P450 reductase, FASEB J. 8:Al244.

    Google Scholar 

  93. Gillette, J. R., 1966, Biochemistry of drug oxidation and reduction by enzymes in hepatic endoplasmic reticulum, Adv. Pharmacol. 4: 219–261.

    Article  PubMed  CAS  Google Scholar 

  94. Rydstrom, J., Montelius, J., and Bengtsson, M., 1983, Extrahepatic Drug Metabolism and Chemical Carcinogenesis, Elsevier, Amsterdam.

    Google Scholar 

  95. Hagland, L., Kohler, C., Haaparanta, T., Goldstein, M., and Gustafsson, J.-A., 1983, Immunohistochemical evidence for a heterogeneous distribution of NADPH-cytochrome P450 reductase in the rat and monkey brain, in: Extrahepatic Drug Metabolism and Chemical Carcinogenesis ( J. Rydström, J. Montelius, and M. Bengtsson, eds.), Elsevier, Amsterdam, pp. 89–93.

    Google Scholar 

  96. McMillan, K., Bredt, D. S., Hirsch, D. J., Snyder, S. H., Clark, J. E., and Masters, B. S. S., 1992, Cloned expressed rat cerebellar nitric acid synthase contains stoichiometric amounts of heme which binds carbon monoxide, Proc. Natl. Acad. Sci. USA 89: 11141–11145.

    Article  PubMed  CAS  Google Scholar 

  97. Shet, M. S., Fisher, C. W., Arlotto, M. P., Shackleton, C. H. L., Holmans, P. L., Martin-Wixtrom, C. A., Saeki, Y., and Estabrook, R. W., 1994, Purification and enzymatic properties of a recombinant fusion protein expressed in Escherichia coli containing the domains of bovine P450 17A and rat NADPH cytochrome P450 reductase, Arch. Biochem. Biophys. 311: 402–417.

    Article  PubMed  CAS  Google Scholar 

  98. Murakami, H., Yabusaki, Y., Sakaki, T., Shibata, M., and Ohkawa, H., 1987, A genetically engineered P450 monooxygenase: Construction of the functional used enzyme between rat cytochrome P450 c and NADPH cytochrome P450 reductase, DNA 6: 189–197.

    Article  PubMed  CAS  Google Scholar 

  99. Fisher, C. W., Shet, M. S., Caudle, D. C., Martin-Wixtrom, C. A., and Estabrook, R. W., 1992, High-level expression in Escherichia coli of enzymatically active fusion proteins containing the domains of mammalian cytochromes P450 and NADPH-cytochrome P450 reductase flavoprotein, Proc. Natl. Acad. Sci. USA 89: 10817–10821.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry and Molecular Biology, The University of Texas Medical School at Houston, Houston, Texas, 77225, USA

    Henry W. Strobel, Anne V. Hodgson & Sijiu Shen

Authors
  1. Henry W. Strobel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Anne V. Hodgson
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Sijiu Shen
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pharmaceutical Chemistry, School of Pharmacy, University of California, San Francisco, 94143, San Francisco, California, USA

    Paul R. Ortiz de Montellano

Rights and permissions

Reprints and permissions

Copyright information

© 1995 Springer Science+Business Media New York

About this chapter

Cite this chapter

Strobel, H.W., Hodgson, A.V., Shen, S. (1995). NADPH Cytochrome P450 Reductase and Its Structural and Functional Domains. In: de Montellano, P.R.O. (eds) Cytochrome P450. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-2391-5_7

Download citation

  • DOI: https://doi.org/10.1007/978-1-4757-2391-5_7

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4419-3248-8

  • Online ISBN: 978-1-4757-2391-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation