Бесплатный автореферат и диссертация по биологии на тему

Сравнительное исследование механизмов взаимодействия цитохрома Р450 2В4 и гемового домена монооксигеназы Р450ВМ3 с их партнерами-донорами электронов

ВАК РФ 03.00.04, Биохимия

Содержание диссертации, кандидата биологических наук, Карякин, Андрей Александрович

Список сокращений.

I. Введение.

II. Обзор литературы.

2.1. Р450-содержащие монооксигеназные системы.

2.1.1. Состав и локализация монооксигеназных систем.

2.1.2. Бактериальная монооксигеназа ВМЗ из В. megaterium.

2.1.2.1. Редуктазный домен.

2.1.2.2. Гемовый домен.

2.1.3. Микросомальная монооксигеназа.

2.1.3.1. NADPH-цитохром Р450 редуктаза.

2.1.3.2. Цитохром Р450.

2.2. Белок-белковые взаимодействия в монооксигеназных системах.

2.2.1. Роль заряженных аминокислотных остатков в межмолекулярных взаимодействиях компонентов ММО.

2.2.2. Роль заряженных аминокислотных остатков в междоменовых взаимодействиях компонентов бактериальной монооксигеназы ВМЗ.

2.3. Теоретический анализ описания электростатических взаимодействий.

2.4. Применение метода инфракрасной спектроскопии для изучения структуры белков и их комплексов.>.

5. Методы регистрации белок-белковых взаимодействий.

III. Материалы и методы.

3.1 Реактивы, реагенты и ферменты.

3.2 Аналитические методы.

3.3 Кинетические методы.

3.4 Метод химической модификации.:.

3.5 Регистрация образования комплексов цитохром Р450-редуктаза методом резонансного переноса энергии.

3.6. Метод инфракрасной спектроскопии с преобразованием Фурье.

IV. Результаты.

4.1. Сравнительное исследование взаимодействий редокс партнеров ММО и бактериальной монооксигеназы ВМЗ различными методами.

4.2. Исследование влияния электростатических сил на процессы образования комплексов цитохромов Р450 2В4 и BMP с NCPRcpm и ВМЗсрм.

4.3. Применение модели «параллельные поверхности» для описания зависимостей Kd комплексов 2B4-NCPR, 2B4-BMR, BMP-BMR и ВМР-NCPR от ионной силы среды.

4.4. Восстановление цитохромов Р450 чужеродными редуктазами: гемового домена BMP микросомальной NCPR и 2В4 бактериальной редуктазой BMR.

4.5. Применение ИК-спектроскопии для исследования конформационных переходов в гемовом и FMN-содержащем доменах бактериальной монооксигеназы ВМЗ при их комплексообразовании.

4.5.1. Определение изменения процентного содержания вторичных структур BMP и FMND при комплексообразовании путем описания ИК-спектров функциями Гаусса.

4.5.2. Определение структурных изменений в молекулах BMP и FMND при комплексообразовании путем титрования FMND гемовым доменом и анализа данных методом главных компонент.

V. Обсуждение результатов.

Выводы.

Заключение Диссертация по теме "Биохимия", Карякин, Андрей Александрович

6. Выводы.

1. В образовании функционально-активного комплекса переноса электронов между цитохромом Р450 2В4 и NADPH-зависимой цитохром Р450 редуктазой важную роль играют электростатические взаимодействия, которые могут быть описаны как взаимодействие двух противоположно заряженных центров связывания радиусом 8 А и, предположительно, сопровождаются образованием 3-4 солевых мостиков.

2. Гемовый и флавиновый домены Р450ВМЗ характеризуются достаточно низким сродством друг к другу (Kd = 3.5 цМ), причём взаимодействия между ними затруднено некоторым электростатическим отталкиванием, которое может быть описано как взаимодействие двух одинаково заряженных участков диаметром 6.5 А.

3. Компоненты микросомальной и бактериальной МОС взаимодействуют между собой с образованием функционально-активных смешанных комплексов. Различия между ММО и Р450ВМЗ во вкладе электростатических взаимодействий в образование комплекса переноса электрона обусловлены, прежде всего, особенностями структур 2В4 и BMP.

4. Скорость переноса электронов в комплексах цитохрома Р450 2В4 и гемового домена Р450ВМЗ с микросомальной редуктазой и BMR определяется природой флавопротеина. BMR является более эффективным донором электронов как для 2В4, так и для BMP.

5. Разработан новый подход для изучения структурных изменений в белках при комплексообразовании методом ИК-спектроскопии с преобразованием Фурье. Его применение в исследовании белок-белковых взаимодействий в МОС показало, что образование комплекса BMP с FMND сопровождается формированием солевого мостика His-Glu и разрывом внутримолекулярного солевого мостика с участием остатка тирозина, а также заметными конформационными переходами в молекулах обоих белков.

104

Библиография Диссертация по биологии, кандидата биологических наук, Карякин, Андрей Александрович, Москва

1. Арчаков А.И., Карякин А.В., Скулачев В.П. 1975. Транспортные процессы вдоль биологических мембран (латеральный перенос). Докл. АН СССР. Т. 222 стр. 14601462;

2. Арчаков АИ, Карякин АВ, Изотов MB, Скулачев ВП. 1976. Перенос электронов между изолированными гепатоцитами, Докл. АН СССР, Т. 230, стр. 462-465;

3. Карякин А.В., Арчаков А.И., 1981. Межмембранный перенос электронов. Успехи современной биологии. Т. 91 стр. 74-89;

4. Уваров ВЮ, Скоцеляс ЕД, Бачманова ГИ, Арчаков АИ. 1983. Конформационное состояние и функциональная активность изолированной и встроенной в фосфолипидный бислой NADPH-зависимой цитохром Р450 редуктазы. Биохимия. Т. 48 стр. 1168-1171;

5. Alberty RA and Hammes CG. 1958. Application of the theory of diffusion controlled reactions to enzyme kinetics. J. Phys. Cnem. V. 62 pp. 154-159;

6. Amis ES and Jaffe G. 1942. The Derivation of a general kinetic equation for reaction between ions and dipolar molecules. J. Chem. Phys. V. 10 pp. 598-604;

7. Archakov AI and Bachmanova GI. 1990. Cytochrome P450 and active oxygen. Taylor&Francis. London;

8. Archakov AI, Borodin EA, Davydov DR, Karyakin AV, Borovyagin VL. 1982 Dec 15. Random distribution of NADPH-specific flavoprotein and cytochrome P-450 in liver microsomes. Biochem. Biophis. Res. Commun. V. 109(3) pp. 832-40;

9. Archakov AI, Karyakin AV, Skulachev VP. 1975 Nov 11. Intermembrane electron transport in the absence of added water-soluble carriers. Biochim. Biophis. Acta. V. 408(2) -pp. 93-100;

10. Arrondo JL and Goni FM. 1999. Structure and dynamics of membrane proteins as studied by infrared spectroscopy. Prog. Biophys. Mol. Biol. V. 72(4) pp. 367-405;

11. Arrondo JL, Young NM and Mantsch HH. 1988 Feb 10. The solution structure of concanavalin A probed by FT-IR spectroscopy. Biochim. Biophys. Acta. V. 952(3) pp. 261-8;

12. Bernhard R, Makower A, Janig GR and Ruckpaul K. 1984 Mar 29. Selective chemical modification of a functionally linked lysine in cytochrome P-450 LM2. Biochem. Biophys. Acta. V. 785(3)-pp. 186-90;

13. Bernhardt R, Kraft R and Ruckpaul K. 1988 Dec. A simple determination of the sideness of the NH2-terminus in the membrane bound cytochrome P-450 LM2. Biochem. Int. V. 17(6)-pp. 1143-50;

14. Bernhardt R, Kraft R, Otto A and Ruckpaul K. 1988. Electrostatic interactions between cytochrome P-450 LM2 and NADPH-cytochrome P-450 reductase. Biomed. Bioshim. Acta. V. 47(7)-pp. 581-92;

15. Bernhardt R, Ngoc-Dao NT, Stiel H, Schwarze W, Friedrich J, Janig GR and Ruckpaul K. 1983 Jun 15. Modification of cytochrome P-450 with fluorescein isothiocyanate. Biochim. Biophys. Acta. V. 745(2) pp. 140-8;

16. Bernhardt R, Pommerening К and Ruckpaul K. 1987 May. Modification of carboxyl groups on NADPH-cytochrome P-450 reductase involved in binding of cytochromes с and P-450 LM2. Biochem. Int. V. 14(5) pp. 823-32;

17. Black SD and Coon MJ. 1982. Structural features of liver microsomal NADPH cytohrome P450 reductase: Hydrophobic domain, hydrophilic domain and connecting region. J. Biol. Chem. V. 257-pp. 5929-38;

18. Black SD, French JS, Williams CH and Coon MJ. 1979 Dec 28. Role of a hydrophobicpolypeptide in the N-terminal region of NADPH-cytochrome P-450 reductase in complexformation with P-450LM. Biochem. Biophys. Res. Commun. V. 91(4) pp. 1528-35;

19. Boddupalli SS, Estabrook RW and Peterson JA. 1990. Fatty acid monooxygenation bycytochrome P-450BM-3. J. Biol. Chem. V. 265(8) pp. 4233-39;

20. Bridges A, Gruenke L, Chang YT, Vakser IA, Loew G and Waskell L. 1998 Jul 3.1.entification of the binding site on cytochrome P450 2B4 for cytochrome b5 andcytochrome P450 reductase. J. Biol. Chem. V. 273(27) pp. 17036-49;

21. Byler DM and Susi H. 1986 Mar. Examination of the secondary structure of proteins bydeconvolved FTIR spectra. Biopolymers. V. 25(3) pp. 469-87;

22. Cawley GF, Batie С J and Backes WL. 1995 Jan 31. Substrate-dependent competition of different P450 isozymes for limiting NADPH-cytochrome P450 reductase. Biochemistry. V. 34(4)-pp. 1244-7;

23. Champion PM and Gunsalus 1С. 1977 Mar 16. Resonance Raman spectra of cytochrome P450cam letter. J. Am. Chem. Soc. V. 99(6) pp. 2000-2;

24. Chang YT and Loew GH. 1999 Jun. Molecular dynamics simulations of P450 BM3-examination of substrate-induced conformational change. J. Biomol. Struct. Dyn. V. 16(6) -pp. 1189-203;

25. Chazotte В and Hackenbrok CR. 1989 Mar 25. Lateral diffusion as a rate-limiting step in ubiquinone-mediated mitochondrial electron transport. J. Biol. Chem. V. 264(9) pp. 4978-85;

26. Chiang YL and Coon MJ. 1979 Jun. Comparative study of two highly purified forms of liver microsomal cytochrome P-450: circular dichroism and other properties. Arch. Biochem. Biophys. V. 195(1)-pp. 178-87;

27. Chirgadze YN, Fedorov OV and Trushina NP. 1975 Apr. Estimation of amino acid residue side-chain absorption in the infrared spectra of protein solutions in heavy water. Biopolymers. V. 14(4) pp. 679-94;

28. Susceptibility and Prevention of Environmental Disease. (Snyder R, et al., Eds.), Kluwer Academic/ Plenum Publishers, in press.;

29. Debye P and Huckel E. 1923. Zur Theorie der Elektrolyte. Phys Z. V. 24 pp. 185-206; Debye P. 1942. Reaction rates in ionic solutions. Trans. Electrochem. Soc. V. 82 - pp. 265-272;

30. Dignam J.D., Strobel H.W., 1977, NADPH-cytochrome P-450 reductase from rat liver: purification by affinity chromatography and characterization, Biochemistry, V. 16(b) pp. 1116-2;

31. Di-Primo C, Sligar SG, Hoa GH and Douzou P. 1992 Nov 9. A critical role of protein-bound water in the catalytic cycle of cytochrome P-450 camphor. FEBS Lett. V. 312(2-3) -pp. 252-4;

32. Dollinger G, Eisenstein L, Lin SL, Nakanishi K, Odashima К and Termini J. 1986. Bacteriorhodopsin: fourier transform infrared methods for studies of protonation of carboxyl groups. Methods. Ensymol. V. 127 pp. 649-62;

33. Fouss R. 1934. Influence of dipol fields between solute molecules. I. On osmotic properties. J. Am. Chem. Soc. V. 56 pp. 1027-30;

34. Gavindaraj S and Poulos TL. 1997 Mar 21. The domain architecture of cytochrome P450BM-3. J. Biol. Chem. V. 272(12) pp. 7915-21;

35. Gibson GG and Tamburini PP. 1986 May. Chemical modification of the histidine residues of purified hepatic cytochrome P-450: influence on substrate binding and the haemoprotein spin state. Chem. Biol. Interact. V. 58(2) pp. 185-98;

36. Gregoriou VG, Jayaraman V, Ни X and Spiro TG. 1995 May 23. FT-IR differencespectroscopy of hemoglobins A and Kempsey: evidence that a key quaternary interactioninduces protonation of Asp beta 99. Biochemistry. V. 34(20) pp. 6876-82;

37. Gruenke LD, Konopka K, Cadieu M and Waskell L. 1995 Oct 20. The stoichiometry of thecytochrome Р-450-catalyzed metabolism of methoxyflurane and benzphetamine in thepresence and absence of cytochrome b5. J. Biol. Chem. V. 270(42) pp. 24707-18;

38. Gum JR and Strobel HW. 1981. Isolation of the membrane-binding peptide of NADPHcytochrome P450 reductase. J. Biol. Chem. V. 256 pp. 7478-86;

39. Hammes GG and Alberty RA. 1959. The influence of the net protein charge on the rate offormation of enzyme-substrate complexes. J. Phys. Chem. V. 63 pp.274-9;

40. Hare RS and Fulco AJ. 1975. Carbon monoxide and hydroxymercuribenzoat sensitivity ofa fatty acid (omega-2) hydroxylase from Bacillus megaterium. Biochem. Biophys. Res.

41. Commun. V. 65(2) pp. 665-72;

42. Hasemann CA, Kurumbail RG, Boddupally SS, Peterson JA and Deisenhofer J. 1995 Jan 15. Structure and function of cytochromes P450: a comparative analysis of three crystal structures. Structure. V. 3(1) pp. 41-62;

43. Hazzard JT, Rong S and Tollin G. 1991. Ionic strength dependence of the kinetics of electron transfer from bovine mitochondrial cytochrome с to bovine cytochrome oxidase. Biochemistry. V. 30 pp. 213-22;

44. Heinemann FS and Ozols J. 1983 Apr 10. The complete amino acid sequence of rabbit phenobarbital-induced liver microsomal cytochrome P-450. J. Biol. Chem. V. 258(7) -pp.4195-201;

45. Jung С, Ristau О, Schulze H and Sligar SG. 1996 Feb 1. The CO stretching mode infrared spectrum of substrate-free cytochrome P-450cam-CO: the effect of solvent conditions, temperature, and pressure. Eur. J. Biochem. V. 235(3) pp. 660-9;

46. Jung C. 2000 Nov-Dec. Insight into protein structure and protein-ligand recognition by Fourier transform infrared spectroscopy. J. Mol. Recognit. V. 13(6) pp. 325-51;

47. Katagiri M, Murakami H, Yabusaki Y, Sugiyama T, Okamoto M, Yamano T and Ohkawa H. 1986. Molecular cloning and sequence analysis of full-lingth cDNA for rabbit liver NADPH-cytochrome P-450 reductase m-RNA. J. Biochem. V. 100 pp. 945-954;

48. Klein ML and Fulco AJ. 1993 Apr 5. Critical residues involved in FMN binding and catalytic activity in cytochrome P450BM-3. J. Boil. Chem. V. 268(10) pp. 7553-61;

49. Knapp ID and Sirobel HW. 1977. NADPH-cytochrome P450 reductase from rat liver: purification by affinity chromatography and characterization. Biochemistry. V. 16 pp. 1116-1123;

50. Knapp JA, Dignam HW and Strobel HW. 1977. NADPH-cytochrome P450 reductase: circular dichroism and physical properties. J. Biol. Chem. V. 252 pp. 437—443;

51. Koppenol WH. 1980. Effect of a molecular dipole on the ionic strength dependence of a bimolecular rate constant. Biophys. J. V. 29 pp. 493-508;1.l

52. Krimm S and Bandekar J. 1986. Vibrational spectroscopy and conformation of peptides, polypeptides, and proteins. Adv. Protein. Chem. V. 38 pp. 181-364;

53. Li H and Poulos TL. 1996. Conformational dynamics in cytochrome P450-substrate interactions. Biochimie. V. 78(8-9) pp. 695-9;

54. Li H and Poulos TL. 1999 Nov 23. Fatty acid metabolism, conformational change, and electron transfer in cytochrome P-450(BM-3). Biochim. Biophys. Acta. V. 1441(2-3) pp. 141-9;

55. Liccione JJ and Mains MD, 1989. Alteration of microsomal and mitochondrial cytochrome P450 and drug metabolism activity in rat brain by managanese, Cytochrome P450: Biochemistry and Biophysics (Shuster I., edc.). Taylor&London etc. pp. 146-149;

56. Malinowski ER and Howery DG. 1980. Factor analysis in Chemistry. Willey-Interscience. New York;

57. Masters BS and Okita RT. 1980. The history, properties and function of NADPH-cytochome P450 reductase. In: Hepatic cytochrome P450 monooxygenase system (Schenkman JB, Kupfer D, eds.) Perggamon press. Oxford ets. - pp. 342-360;

58. Matson RS, Hare RS and Fulco AJ. 1977. Characteristics of a cytochrome P-450-dependent fatty acid omega-2 hydroxylase from Bacillus megaterium. Biochim. Biophys. Acta. V. 487(3)-pp. 487-94;

59. Mayuzumi H, Sambongi C, Hiroya K, Shimizu T, Tateishi T and Hatano M. 1993 Jun 1. Effect of mutations of ionic amino acids of cytochrome P450 1A2 on catalytic activities toward 7-ethoxycoumarin and methanol. Biochemistry. V. 32(21) pp. 5622-8;

60. Meyer ТЕ, Watkins JA, Przysiecki CT, Tollin G and Cusanovich MA. 1984. Electron-transfer reactions of photoreduced flavins analogues with c-type cytochromes: Quantitation of steric and electrostatic factors. Biochemistry. V. 23 pp. 4761-7;

61. Minor J. Coon and Anders V. Persson. 1980. Microsomal Cytochrome P-450: A Central Catalist in Detoxication Reactions. Enzymatic Basis of Detoxication. V.l pp. 117-134;112

62. Miura Y and Fulco AJ. 1974. (Omega-2) hydroxylation of fatty acids by a soluble system from Bacillus megaterium. J. Biol. Chem. V. 249(6) pp. 1880-88;

63. Mima Y and Fulco AJ. 1975. Omega-1, omega-2 and omega-3 hydroxylation of long-chain fatty acids, amids and alcohols by a soluble enzyme system from Bacillus megaterium. Bioch. Bioph. Acta. V. 388(3)-pp. 306-17;

64. Mouro C, Jung C, Bondon A and Simonneaux G. 1997 Jul 1. Comparative Fourier transform infrared studies of the secondary structure and the CO heme ligand environment in cytochrome P-450cam and cytochrome P-420cam. Biochemistry. V. 36(26) pp. 812534;

65. Myasoedova KN and Berndt P. 1990 Nov 26. Cytochrome P-450LM2 oligomers in proteoliposomes. FEBS-Lett. V. 275(1-2): 235-8;

66. Myasoedova KN and Tsuprun VL. 1993 Jul 5. Cytochrome P-450: hexameric structure of the purified LM4 form. FEBS-Lett. V. 325(3) pp. 251-4;

67. Nadler SG and Strobel HW. 1988 Mar. Role of electrostatic interactions in the reaction of NADPH-cytochrome P-450 reductase with cytochromes P-450. Arch. Biochem. Biophys. V. 261(2)-pp. 418-29;

68. Nadler SG and Strobel HW. 1991 Nov 1. Identification and characterization of an NADPH-cytochrome P450 reductase derived peptide involved in binding to cytochrome P450. Arch. Biochem. Biophys. V. 290(2) pp. 277-84;

69. Narhi LO and Fulco AJ. 1982. Phenobarbital induction of a soluble cytochrome P-450-dependent fatty acid monooxygenase in Bacillus megaterium. J. Biol. Chem. V. 257(5) -pp. 2147-50;

70. Narhi LO and Fulco AJ. 1986. Characterization of a catalytically self-sufficient 119.00-dalton cytochrome P-450 monooxygenase induced by barbiturates in Bacillus megaterium.// Journal of Biological Chemistry. V. 261. No. 16. - pp. 7160-7169;

71. Narhi LO and Fulco AJ. 1987. Identification and characterization of two functional domains in cytochrome Р-450вм-з, a catalytically self-sufficient monooxigenase induced by barbiturates in Bacillus megaterium. J. Biomed. Chem. V.262(14) pp. 6683-90;

72. Narhi LO, Kim BH, Stevenson PM and Fulco AJ. 1983. Partial characterization of a barbiturate-induced cytochrome Р-450-dependent fatty acide monooxigenase from Bacillus megaterium. Biochem. Biophys. Res. Commun. V. 116(3) pp. 851-58;

73. Nisimoto Y and Lambeth JD. 1985 Sep. NADPH-cytochrome P-450 reductase-cytochrome b5 interactions: crosslinking of the phospholipid vesicle-associated proteins by a water-soluble carbodiimide. Arch. Biochem. Biophys. V. 241(2): 386-96;

74. Nisimoto Y and Otsuka-Murakami H. 1988 Aug 9. Cytochrome b5, cytochrome c, and cytochrome P-450 interactions with NADPH-cytochrome P-450 reductase in phospholipid vesicles. Biochemistry. V. 27(16)-pp. 5869-76;

75. Nisimoto Y, Kinosita К Jr, Ikegami A, Kawai N, Ichihara I and Shibata Y. 1983 Jul 19. Possible association of NADPH-cytochrome P-450 reductase and cytochrome P-450 in reconstituted phospholipid vesicles. Biochemistry. V. 22(15) pp. 3586-94;

76. Nisimoto Y. 1986 Oct 25. Localization of cytochrome c-binding domain on NADPH-cytochrome P-450 reductase. J. Biol. Chem. V. 261(30) pp. 14232-9;

77. Omura T and Sato R. 1964. The carbon monoxide-binding pigment of liver microsomes. J. Biol. Chem. V. 239 pp. 2370-85;

78. Onsager L. 1936. Electric moments of molecules and liquids. J. Am. Chem. Soc. V. 58 -pp. 1486-93;

79. Ortiz de Montellano PR, Kunze KL, Beilan HS. 1983. Chiral orientation of heme in the cytochromeP-450 active site. J. Biol. Chem. V. 258 pp. 45-47;

80. Pesce AJ, Rosen CG and Pasby TL. 1971. Fluorescence spectroscopy. Marcel Dekker Inc. New York;

81. Peterson JA and Graham-Lorence SE. 1995. Cytochrome P450: Structure, Mechanism, and Biochemistry, pp. 151-180;

82. Peterson JA, Ebel RE, O'Keeffe DH, Matsubara T and Estabrook RW. 1976 Jul 10. Temperature dependence of cytochrome P-450 reduction. A model for NADPH114cytochrome P-450 reductasercytochrome P-450 interaction. J. Biol. Chem. V. 251(13) -pp. 4010-6;

83. Peterson JA, Sevrioukova I, Truan G, Graham-Lorence SE. 1997 Jan. P450BM-3; a tale of two domains—or is it three? Steroids. V. 62(1) pp. 117-23;

84. Porter TD and Kasper CB. 1986 Apr 8. NADPH-cytochrome P-450 oxidoreductase: flavin mononucleotide and flavin adenine dinucleotide domains evolved from different flavoproteins. Biochemistry. V. 25(7) pp. 1682-7;

85. Porter TD. 1991. An unusual yet strongly conserved flavoprotein reductase in bacteria and mammals. Trends. Biochem. Sci. V. 16(4) pp. 154-8;

86. Poulos TL, Finzel ВС and Howard AJ. 1986 Sep 9. Crystal structure of substrate-free Pseudomonas putida cytochrome P-450. Biochemistry. V. 25(18) pp. 5314-22;

87. Presnell SR and Cohen FE. 1989. Topological distribution of four-alpha-helix bundles. Natl.Acad.Sci. USA V. 86 pp. 6592-6;

88. Rees DC. 1980. Experimental evolution of the effective dielectric constant constants of proteins. J. Mol. Biol. V. 141 pp. 323-6;

89. Rickle GK and Cusanovich MA. 1979. Experimental evolution of the effective dialectric constant of proteins. Arch. Biochem. Biophys. V. 197 pp.589-98;

90. Rodgers KK, Pochapsky TC and Sligar SG. 1988 Jun 17. Probing the mechanisms of macromolecular recognition: the cytochrome b5-cytochrome с complex. Scince. V. 240(4859)-pp. 1657-9;115

91. Ruettinger RT and Fulco AJ. 1981. Epoxidation of unsaturated fatty acids by a soluble cytochrome Р-450-dependent system from Bacillus megaterium. J. Biol. Chem. V. 256(11) -pp. 5728-34;

92. Ruettinger RT, Wen LP and Fulco AJ. 1989. Coding nucleotide, 5' regulatory, and deduced amino acid sequences of Р-450вм-з, a single peptide cytochrome P-450:NADPH-P-450 reductase from Bacillus megaterium. J. Biol. Chem. V. 264(19) -pp. 10987-95;

93. Salemme FR and Weatherford DW. 1981 Feb 15. Conformational and geometrical properties of beta-sheets in proteins. I. Parallel beta-sheets. J. Mol. Biol. V. 146(1) pp. 101-17;

94. Salemme FR. 1978 Dec 15. Peptide models for the study of coupled conformational properties of protein secondary structures. J. Mol. Biol. V. 126(3) pp. 591-5;

95. Sato M, Коп H, Kumaki К and Nebert DW. 1977 Jul 21. Comparative EPR study on high-spin ferric porphine complexes and cytochrome P-450 having rhombic character. Biochim. Biophys. Acta. V. 498(1)-pp. 403-21;

96. Schen S and Strobel HW. 1992 Apr. The role of cytochrome P450 lysine residues in the interaction between cytochrome P450IA1 and NADPH-cytochrome P450 reductase. V. 294(1)-pp. 83-90;

97. Schenkman JB, Voznesensky AI and Jansson I. 1994 Oct. Influence of ionic strength on the P450 monooxygenase reaction and role of cytochrome b5 in the process. Arch. Biochem. Biophys. V. 314(1) pp. 234-41;

98. Schwarz D, Pirrwitz J, Meyer HW, Coon MJ and Ruckpaul K. 1990 Aug 31. Membrane topology of microsomal cytochrome P-450: saturation transfer EPR and freeze-fracture electron microscopy studies. Biochem. Biophys. Res. Commun. V. 171(1)-pp. 175-81;

99. Sevrioukova and Peterson JA. 1996. Domain-domain interaction in cytochrome P450BM-3. Biochimie. V. 78(8-9) pp. 744-51;

100. Sevrioukova I, Truan G and Peterson JA. 1996 Jun 11. The flavoprotein domain of P450BM-3: expression, purification, and properties of the flavin adenine dinucieotide- and flavin mononucleotide-binding subdomains. Biochemistry. V. 35(23) pp. 7528-35;

101. Sevrioukova IF, Li H, Zhang H, Peterson JA and Poulos TL. 1999 Mar 2. Structure of a cytochrome P450-redox partner electron-transfer complex. Proc. Natl. Acad. Sci. USA. V. 96(5)-pp. 1863-8;

102. Shank-Retzlaff ML, Raner GM, Coon MJ and Sligar SG. 1998 Nov 1. Membrane topology of cytochrome P450 2B4 in Langmuir-Blodgett monolayers. Arch. Biochem. Biophys. V. 359(1)-pp. 82-8;

103. Sharp KA and Honig B. 1990. Electrostatic interactions in macromolecules: theory and applications. Annu. Rev. Biophys. Biophys. Chem. V. 19 pp. 301-32;

104. Shen AL and Kasper CB. 1995 Nov 17. Role of acidic residues in the interaction of NADPH-cytochrome P450 oxidoreductase with cytochrome P450 and cytochrome c. J. Biol. Chem. V. 270(46) pp. 27475-80;

105. Shen AL, Porter TD, Wilson ТЕ and Kasper CB. 1989. Structural analysis of the FMN binding domain of NADPH-cytochrome P-450 oxidoreductase by site-directed mutagenesis. J. Biol. Chem. V. 264(13) pp. 7584-89;

106. Shen S and Strobel HW. 1993 Jul. Role of lysine and arginine residues of cytochrome P450 in the interaction between cytochrome P4502B1 and NADPH-cytochrome P450 reductase. Arch. Biochem. Biophys. V. 304(1) pp. 257-65;

107. Shen S and Strobel HW. 1994 Jul 26. Probing the putative cytochrome P450- and cytochrome c-binding sites on NADPH-cytochrome P450 reductase by anti-peptide antibodies. Biochemistry. V. 33(29)-pp. 8807-12;

108. Sheridan RP and Allen LC. 1981. The active site electrostatic potential of human carbonic anhydrase. J. Am. Chem. Soc. V. 103 pp. 1554-60;

109. Shimizu T, Nozawa T, Hatano M, Satake H, Imai Y, Hashimoto С and Sato R. 1979 Lul 25. Circular dichroism spectra of purified cytochromes P-450 from rabbit liver microsomes. Biochim. Biophys. Acta. V. 579(1) pp. 122-33;

110. Shulze J, Lehnerer M, Lewis DF and Hlavica P. 1998 May. Amino acid residue 250 has a functional role in the assembly of rabbit liver microsomal cytochrome P450 2B4. Biohem.Mol. Biol. Int. V. 44(6) pp. 1147-55;

111. Stayton PS and Sligar SG. 1990 Aug 14. The cytochrome P-450cam binding surface as defined by site-directed mutagenesis and electrostatic modeling. Biochemistry. V. 29(32) -pp. 7381-6;

112. Stayton PS, Poulos TL and Sligar SG. 1989 Oct 3. Putidaredoxin competitively inhibits cytochrome b5-cytochrome P-450cam association: a proposed molecular model for a cytochrome P-450cam electron-transfer complex. Biochemistry. V. 28(20) pp. 8201-5;

113. Stonehuerner G, Williams GB and Millett F. 1979. Interaction between cytochrome с and cytochrome bs Biochemistry. V. 18 pp. 5422-7;

114. Strittmatter P, Rogers MJ. 1975 Jul. Apparent dependence of interactions between cytochrome b5 and cytochrome b5 reductase upon translational diffusion in dimyristoyl lecithin liposomes. Proc. Natl. Acad. Sci. USA. V. 72(7) pp. 2658-61;

115. Strobel HW, Dignam JD and GUM JD. 1980. NADPH-cytochrome P450 reductase and its role in the mixed function oxidase reactions. Pharmacol. Ther. A. V. 8 pp 525-537;

116. Surewicz WK and Mantsch HH. 1988 Jan 29. New insight into protein secondary structure from resolution-enhanced infrared spectra. Biochim. Biophys. Acta. V. 952(2) pp. 11530;

117. Surewicz WK and Mantsch HH. 1996. Infrared absorbtion methods for examining protein structure. In: Spectroscopic Methods for Determining Protein Structure in solution. (Havel HA, ed.) VCH, New York, pp. 135-162;

118. Susi H. and Byler DM. 1986. Resolution-enhanced Fourier transform infrared spectroscopy of enzymes. Methods Ensymol. V. 130 pp. 290-311;118

119. Tamburini PP and Schenkman JB. 1986 Aug. Differences in the mechanism of functional interaction between NADPH-cytochrome P-450 reductase and its redox partners. Mol. Pharmacol. V. 30(2) pp. 178-85;

120. Tamburini PP, MacFarquhar S and Schenkman JB. 1986 Jan 29. Evidence of binary complex formations between cytochrome P-450, cytochrome b5, and NADPH-cytochrome P-450 reductase of hepatic microsomes. Biochem. Biophys. Res. Commun. V. 134(2) pp. 519-26;

121. Tamburini PP, White RE and Schenkman JB. 1985 Apr 10. Chemical characterization of protein-protein interactions between cytochrome P-450 and cytochrome b5. J. Biol. Chem. V. 260(7)-pp;

122. Tret'iakov VE, Degtiarenko KN, Uvarov VI, Archakov AI, Tret'iakova LZ and Varenitsa AI. 1989 Sep-Oct. Structural organization and localization of cytochromes P450 in the membrane. Mol. Biol. Mosk. V. 23(5)-pp. 1321-31;

123. Tuls J, Geren L, Lamberth JD and Millett F. 1987 Jul 25. The use of a specific fluorescence probe to study the interaction of adrenodoxin with adrenodoxin reductase and cytochrome P-450scc. J. Biol. Chem. V. 262(21) pp. 10020-5;

124. Van Leeuwen JW, Mofers FJM and Veerman ECI. 1981. The ionic strength dependence of the rate of a large ion with a dipole moment. Biochim. Biophys. Acta. V. 635 pp. 434-9;

125. Van Leeuwen JW. 1983. The ionic strength dependence of the rate of a reaction between two large proteins with a dipole moment. Biochim. Biophys. Acta. V. 743 pp. 408-21;

126. Voznesensky AI and Schenkman JB. 1992 Dec 15. Inhibition of cytochrome-P450 reductase by polyols has an electrostatic nature. Eur. J. Biochem. V. 210(3) pp. 741-6;

127. Voznesensky AI and Schenkman JB. 1992 Jul 25. The cytochrome P450 2B4-NADPH cytochrome P450 reductase electron transfer complex is not formed by charge-pairing. J. Biol. Chem. V. 267(21) pp. 14669-76;119

128. Voznesensky AI and Schenkman JB. 1994 Jun 3. Quantitative analyses of electrostatic interactions between NADPH-cytochrome P450 reductase and cytochrome P450 enzymes. J. Biol. Chem. V. 269(22) pp. 15724-31;

129. Wada A and Waterman MR. 1992 Nov 15. Identification by site-directed mutagenesis of two lysine residues in cholesterol side chain cleavage cytochrome P4-50 that are essential for adrenodoxin binding. J. Biol. Chem. V. 267(32) pp. 22877-82;

130. Wang M, Roberts DL, Peschke R, Shea TM, Masters ВS and Kim JJ. 1997 Aug 5. Three-dimensional structure of NADPH-cytochrome P450 reductase: prototype for FMN- and FAD-containing enzymes. Proc. Natl. Acad. Sci. USA. V. 94(16) pp. 8411-6;

131. Watkins JA, Cusanovich MA, Meyer ТЕ and Tollin G. 1994 Nov. A "parallel plate" electrostatic model for bimolecular rate constants applied to electron transfer proteins. Protein Sci. V. 3(11) pp. 2104-14;

132. Watkins JA. 1986. Spectral and kinetic properties of Chlorobium thiosulfatophilum cytochrome c-555 thesis. Tucson: University of Arizona;

133. Weber G. 1992. Protein Interactions. Chapman and Hall. New York. London;

134. Wherland S and Gray HB. 1976. Metalloprotein electron transfer reactions: Analysis of reactivity of horse heart cytochrome с with inorganic complexes. Proc. Natl. Acad. Sci. USA. V. 73-pp. 2950-54;

135. White RE and Coon MJ. 1982 Mar 25. Heme ligand replacement reactions of cytochrome P-450. Characterization of the bonding atom of the axial ligand trans to thiolate as oxygen. J. Biol. Chem. V. 257(6) pp. 3073-83;

136. Yanagita K, Sagami I and Shimizu T. 1997 oct 15. Distal site and surface mutations of cytochrome P450 1A2 markedly enhance dehalogenation of chlorinated hydrocarbons. Arch. Biochem. Biophys. V. 346(2) pp. 269-76;

137. Yun CH, Song M, Ahn T and Kim H. 1996 Dec 6. Conformational change of cytochrome P450 1A2 induced by sodium chloride. J. Biol. Chem. V. 271(49) pp. 31312-6;

138. Zhou HX. 1993. Boundary element solution of macromolecular electrostatics: Interaction energy between two proteins. Biophys. J. V. 65 pp. 955-63;

139. Zhukov AA and Archakov AI. 1985 Dec. Stoichiometry of microsomal oxidation reactions. Distribution of redox-equivalents in monooxygenase and oxidase reactions catalyzed by cytochrome P-450. Biokhimiia. V. 50(12) pp. 1939-52.