Negatively cooperative binding properties of human cytochrome P450 2E1 with monocyclic substrates

Current Drug Metabolism

Volumn 13, Issue 7, 2012, Pages 1024-1031

  Ping, Jie ^a   Wang, Ya Jun ^a,b   Wang, Jing Fang ^a,b   Li, Xuan ^b,c   Li, Yi Xue ^b,d   Hao, Pei ^b,e  

^a SHANGHAI JIAO TONG UNIVERSITY   (China)

^b SHANGHAI CENTER FOR BIOINFORMATION TECHNOLOGY   (China)

^c INSTITUTE OF PLANT PHYSIOLOGY AND ECOLOGY   (China)

^d Chinese Academy of Sciences   (China)

^e INSTITUTE PASTEUR OF SHANGHAI   (China)

Author keywords

Cooperative binding properties; Cytochrome P450 enzymes; Drug metabolism; Personalized use of drugs

Indexed keywords

CYTOCHROME P450 2E1; LEUCINE; PHENYLALANINE; THREONINE;

AMINO ACID SEQUENCE; ARTICLE; BINDING SITE; ENZYME ACTIVE SITE; ENZYME SUBSTRATE; ENZYME SUBSTRATE COMPLEX; HUMAN; SEQUENCE ANALYSIS; STRUCTURE ANALYSIS;

AMINO ACID SEQUENCE; BINDING SITES; CYTOCHROME P-450 CYP2E1; HUMANS; MOLECULAR SEQUENCE DATA; PROTEIN BINDING; SUBSTRATE SPECIFICITY;

EID: 84865754108     PISSN: 13892002     EISSN: 18755453     Source Type: Journal    
DOI: 10.2174/138920012802138606     Document Type: Article

References (98)

1. Nebert, D.W.; Russell, D.W. Clinical importance of the cytochromes P450. Lancet, 2002, 360, 1155-1162.
2. Nelson, D.R. Cytochrome P450 and the individuality of species. Arch. Biochem. Biophys., 1999, 369, 1-10.
3. Danielson, P.B. The cytochrome P450 superfamily: biochemistry, evolution and drug metabolism in humans. Curr. Drug Metab., 2002, 3, 561-597.
4. Guengerich, F.P. Cytochrome P450 enzymes in the generation of chemical products. Nat. Rev. Drug Discov., 2002, 1, 359-366.
5. Capdevila, J.H.; Harris, R.C.; Falck, J.R. Microsomal cytochrome P450 and eicosanoid metabolism. Cell. Mol. Life Sci., 2002, 59, 780-789.
6. Ortiz de Montellano, P.R.; de Voss, J.J. Oxidizing species in the mechanism of cytochrome P450. Nat. Prod. Rep., 2002, 19, 477-493.
7. Guengerich, F.P. Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity. Chem. Res. Toxicol., 2001, 14, 611-650.
8. Chefson, A.; Auclair, K. Progress towards the easier use of P450 enzymes. Mol. Biosyst., 2006, 2, 462-469.
9. Sanga, M.; Yunis, I.R.; Tirumalai, P.S.; Bland, T.M.; Banaszewska, M.; Konat, G.W.; Tracy, T.S.; Gannett, P.M.; Callery, P.S. Epoxidation of the methamphetamine pyrolysis produce, trans-phenylpropene, to trans-phenylpropylene oxide by CYP enzymes and stereoselective glutathione adduct formation. Toxicol. Appl. Pharmacol., 2006, 211, 148-156.
10. Isin, E.M.; Guengerich, F.P. Complex reactions catalyzed by cytochrome P450 enzymes. Biochim. Biophys. Acta, 2007, 1770, 314-329.
11. Estabrook, R.W. Steroid hydroxylations: a paradigm for cytochrome P450 catalyzed mammalian monooxygenation reactions. Biochem. Biophys. Res. Commun., 2005, 338, 290-298.
12. Pikuleva, I.A. Cytochrome P450s and cholesterol homeostasis. Pharmacol. Ther., 2006, 112, 761-773.
13. Rosenberg, D.W. Tissue-specific induction of the carcinogen inducible cytochrome P450 isoform, P450 IAI in colonic epithelium. Arch. Biochem. Biophys., 1991, 284, 223-226.
14. Omdahl, J.L.; Bobrovnikova, E.A.; Choe, S.; Dwivedi, P.P; May, B.K. Overview of regulatory cytochrome P450 enzymes of the vitamin D pathway. Steroids, 2001, 66, 381-389.
15. Girhard, M.; Schuster, S.; Dietrich, M.; Durre, P.; Urlacher, V.B. Cytochrome P450 monooxygenase from clostridium acetobutylicum: a new alpha-fatty acid hydroxylase. Biochem. Biophys. Res. Commun., 2007, 362, 114-119.
16. Hines, R. Ontogeny of human hepatic cytochromes P450. J. Biochem. Mol. Toxicol., 2007, 21, 169-175.
17. Guengerich, F.P. Cytochrome P450 and chemical toxicology. Chem. Res. Toxicol., 2008, 21, 70-83.
18. Chen, Q.; Zhang, T.; Wang, J.F.; Wei, D.Q. Advances in human cytochrome P450 and personalized medicine. Curr. Drug Metab., 2011, 12, 436-444.
19. Orengo, C.A.; Michie, A.D.; Jones, D.T.; Swindells, M.B.; Thornton, J.M. CATH: a hierarchic classification of protein domain structures. Structure, 1997, 5, 1093-1108.
20. Wang, J.F.; Zhang, C.C.; Chou, K.C.; Wei, D.Q. Structure of cytochrome P450s and personalized drug. Curr. Med. Chem., 2009, 16, 232-244.
21. Johnson, E.F.; Stout, C.D. Structural diversity of human xenobiotic-metabolizing cytochrome P450 monooxygenases. Biochem. Biophys. Res. Commun., 2005, 338, 331-336.
22. Otyepka, M.; Skopalik, J.; Anzenbacherova, E.; Anzenbacher, P. What common structural features and variations of mammalian P450s are known to data? Biochim. Biophys. Acta, 2007, 1770, 376-389.
23. Wang, J.F.; Chou, K.C. Molecular modeling of cytochrome P450 and drug metabolism. Curr. Drug Metab., 2010, 11, 342-346.
24. Kemper, B. Structural basis for the role in protein folding of conserved proline-rich regions in cytochromes P450. Toxicol. Appl. Pharmacol., 2004, 199, 305-315.
25. Meunier, B.; de Visser, S.; Shaik, S. Mechanism of oxidation reactions catalyzed by cytochrome P450 enzymes. Chem. Rev., 2004, 104, 3947-3980.
26. Gunsalus, I.C.; Lipscomb, J.D.; Marshll, V.; Frauenfelder, H.; Greenbaum, E.; Münck, E. Structure and reactions of oxygenase active centers: cytochrome P-450 and iron sulfur proteins. Bio-chem. Soc. Symp., 1972, 34, 135-157.
27. Karki, S.B.; Dinnocenzo, J.P. On the mechanism of amine oxida-tions by P450. Xenobiotica, 1995, 25, 711-724.
28. Sharp, R.E.; Chapman, S.K. Mechanisms for regulating electron transfer in multi-centre redox proteins. Biochim. Biophys. Acta, 1999, 1432, 143-158.
29. Lauren, T.; Jensen, K.; Møller, B.L. Conformational changes of the NADPH-dependent cytochrome P450 reductase in the course of electron transfer to cytochromes P450. Biochim. Biophys. Acta, 2001, 1814, 132-138.
30. Hamdane, D.; Zhang, H.; Hollenberg, P. Oxygen activation by cytochrome P450 monooxygenase. Photosynth. Res., 2008, 98, 657-666.
31. Hannemann, F.; Bichet, A.; Ewen, K.M.; Bernhardt, R. Cyto-chrome P450 systems: biological variations of electron transport chains. Biochim. Biophys. Acta, 2007, 1770, 330-344.
32. Gutierrez, A.; Grunau, A.; Paine, M.; Munro, A.W.; Wolf, C.R.; Roberts, G.C.; Scrutton, N.S. Electron transfer in human cyto-chrome P450 reductase. Biochem. Soc. Trans., 2003, 31, 497-501.
33. Ioannides, C.; Lewis, V.; David, F. Cytochromes P450 in the bio-activation of chemicals. Curr. Top. Med. Chem., 2004, 4, 1767-1788.
34. Bièche, I.; Narjoz, C.; Asselah, T.; Vacher, S.; Marcellin, P.; Lide-reau, R.; Beaune, P.; de Wazjers, I. Reverse transcriptase-PCR quantification of mRNA levels from cytochrome (CYP)1, CYP2 and CYP3 families in 22 different human tissues. Pharmacogenet. Genomics, 2007, 17, 731-742.
35. Shimada, T.; Yamazaki, H.; Mimura, M.; Inui, Y.; Guengerich, F.P. Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J. Pharmacol. Exp. Ther., 1994, 270, 414-423.
36. Nanji, A.A.; Zhao, S.; Sadrzadeh, S.M.; Dannenberg, A.J.; Tahan, S.R.; Waxman, D.J. Markedly enhanced cytochrome P450 2E1 in-duction and lipid peroxidation is associated with severe liver injury in fish oil-ethanol-fed rats. Alcohol Clin. Exp. Res., 1994, 18, 1280-1285.
37. Barnett, C.R.; Rudd, S.; Flatt, P.R.; Ioannides, C. Sex differences in the diabetes-induced modulation of rat hepatic cytochrome P450 proteins. Biochem. Pharmacol., 1993, 45, 313-319.
38. Raucy, J.L.; Lasker, J.M.; Kraner, J.C.; Salazar, D E.; Lieber, C.S.; Corcoran, G.B. Induction of cytochrome P450IIE1 in the obese overfed rat. Mol. Pharmacol., 1991, 39, 275-280.
39. Johansson, I.; Ekstrom, G.; Scholte, B.; Puzycki, D.; Jornvall, H.; Ingelman-Sundberg, M. Ethanol-, fasting-, and acetone-inducible cytochromes P-450 in rat liver: regulation and characteristics of enzymes belonging to the IIB and IIE gene subfamilies. Biochem-istry, 1988, 27, 1925-1934.
40. Trafalis, D.; Panteli, E.; Grivas, A.; Tsigris, C.; Karamanakos, P. CYP2E1 and risk of chemically mediated cancers. Expert. Opin. Drug Metab. Toxicol., 2010, 6, 307-319.
41. Nanji, A.; Zhao, S.; Sadrzadeh, S.; Dannenberg, A.; Tahan, S.; Waxman, D. Markedly enhanced cytochrome P450 2E1 induction and lipid peroxidation is associated with severe liver injury in fish Oil-ethanol-fed rats. Alcohol. Clin. Exp. Res., 1994, 18, 1280-1285.
42. Wang, J.F.; Wei, D.Q.; Chou, K.C. Pharmacogenomics and per-sonalized use of drugs. Curr. Top. Med. Chem., 2008, 8, 1573-1579.
43. Robertson, G.; Leclercq, I.; Farrell, G. Nonalcoholic steatosis and stetohepatitis: II. Cytochrome P450 enzymes and oxidative stress. Am. J. Physiol. Gastrointest. Liver Physiol., 2001, 281, G1135-G1139.
44. Lewis, D.; Bird, M.G.; Parke, D.V. Molecular modeling of CYP2E1 enzymes from rat, mouse and man: an explanation for species differences in butadiene metabolism and potential carcino-genicity, and rationalization of CYP2E substrate specificity. Toxi-cology, 1997, 118, 93-113.
45. Koop, D. Hydroxylation of p-nitrophenol by rabbit ethanol-inducible cytochrome P-450 isozyme 3a. Mol. Pharmacol., 1986, 29, 399.
46. Peter, R.; Boecker, R.; Beaune, P.; Iwasaki, M.; Guengerich, F.; Yang, C. Hydroxylation of chlorzoxazone as a specific probe for human liver cytochrome P-450IIE1. Chem. Res. Toxicol., 1990, 3, 566-573.
47. Laethem, R.; Halpert, J.; Koop, D. Epoxidation of arachidonic acid as an active-site probe of cytochrome P-450 2B isoforms. Biochim. Biophys. Acta, 1994, 1206, 42-48.
48. Roy, U.; Joshua, R.; Stark, R.; Balazy, M. Cytochrome P450/NADPH-dependent biosynthesis of 5, 6-transepoxyeicosatrienoic acid from 5, 6-trans-arachidonic acid. Biochem. J., 2005, 390, 719.
49. Wang, J.F.; Wei, D.Q.; Chou, K.C. Drug candidates from traditional Chinese medicines. Curr. Top. Med. Chem., 2008, 8, 1656-1665.
50. Wang, J.F.; Wei, D.Q. Role of structural bioinformatics and traditional Chinese medicine databases in pharmacogenomics. Pharmacogenomics 2009, 10, 1213-1215.
51. Westbrook, J.; Feng, Z.; Chen, L.; Yang, H.; Berman, H.M. The Protein Data Bank and structural genomics. Nucleic Acids Res., 2003, 31, 489-491.
52. Henrick, K.; Feng, Z.; Bluhm, W.F.; Dimitropoulos, D.; Doreleijers, J.F.; Dutta, S.; Flippen-Anderson, J.L.; Lonides, J.; Kamada, C.; Krissinel, E.; Lawson, C.L.; Markley, J.L.; Nakamura, H.; Newman, R.; Shimizu, Y.; Swaminathan, J.; Velankar, S.; Ory, J.; Ulrich, E.L.; Vranken, W.; Westbrook, J.; Yamashita, R.; Yang, H.; Young, J.; Yousufuddin, M.; Berman, H.M. Remediation of the protein data bank archive. Nucleic Acids Res., 2008, 36, D426-D433.
53. Rose, P.W.; Beran, B.; Bi, C.; Bluhm, W.F.; Dimitropoulos, D.; Goodsell, D.S.; Prlic, A.; Quesada, M.; Quinn, G.B.; Westbrook, J.D.; Young, J.; Yukich, B.; Zardecki, C.; Berman, H.M.; Bourne, P.E. The RCSB Protein Data Bank: redesigned web site and web services. Nucleic Acids Res., 2011, 39, D392-D401.
54. Porubsky, P.R.; Meneely, K.M.; Scott, E.E. Structures of human cytochrome P-450 2E1: Insights into the binding of inhibitors and both small molecular weight and fatty acid substrates. J. Biol. Chem., 2008, 283, 33698-33707.
55. Porubsky, P.R.; Battaile, K.P.; Scott, E.E. Human cytochrome P450 2E1 structures with fatty acid analogs reveal a previously unobserved binding mode. J. Biol. Chem., 2010, 285, 22282-22290.
56. Bell-Parikh, L.C.; Guengerich, F.P. Kinetics of cytochrome P450 2E1-catalyzed oxidation of ethanol to acid via acetaldehyde. J. Biol. Chem., 1999, 274, 23833-23840.
57. Szczesna-Skorupa, E.; Chen, C.D.; Kemper, B. Cytochromes P450 2C1/2 and P450 2E1 are retained in the endoplasmic reticulum membrane by different mechanisms. Arch. Biochem. Biophys., 2000, 374, 128-136.
58. Wang, J.F.; Yan, J.Y.; Wei, D.Q.; Chou, K.C. Binding of CYP2C9 with diverse drugs and its implications for metabolic mechanism. Med. Chem., 2009, 5, 263-270.
59. Morel, Y.; de Waziers, I.; Barouki, R. A repressive crossregulation between catalytic and promoter activities of the CYP1A1 and CYP2E1 genes: role of H(2)O(2). Mol. Pharmacol., 2000, 57, 1158-1164.
60. Li, J.; Wei, D.Q.; Wang, J.F.; Li, Y.X. A negative cooperativity mechanism of human CYP2E1 inferred from molecular dynamics simulations and free energy calculations. J. Chem. Inf. Model., 2011, 51, 3217-3225.
61. Kim, J.Y.; Beak, M.; Lee, S.; Kim, S.O.; Dong, M.S.; Kim, B.R.; Kim, D.H. Characterization of the selectivity and mechanism of cytochrome P450 inhibition by dimethly-4,4'-dimethoxy-5,6,5',6'-dimethylenedioxybiphenyl-2,2'- dicarboxylate. Drug Metab. Dispos., 2001, 29, 1550-1560.
62. Wang, J.F.; Wei, D.Q.; Li, L.; Zheng, S.Y.; Li, Y.X.; Chou, K.C. 3D structure modeling of cytochrome P450 2C19 and its implication for personalized drug design. Biochem. Biophys. Res. Commun., 2007, 355, 513-519.
63. Erratum in: Biochem. Biophys. Res. Commun., 2007, 357, 330.
64. Biochem. Biophys. Res. Commun., 2009, 384, 399.
65. Wang, J.F.; Wei, D.Q.; Chen, C.; Li, Y.; Chou, K.C. Molecular modeling of two CYP2C19 SNPs and its implications for personalized drug design. Protein Pept. Lett., 2008, 15, 27-32.
66. Miller, G.P. Advances in the interpretation and prediction of CYP2E1 metabolism from a biochemical perspective. Expert. Opin. Drug Metab. Toxicol., 2008, 4, 1053-1064.
67. Atkins, W. Non-Michaelis-Menten kinetics in cytochrome P450-catalyzed reactions. Ann. Rev. Pharmacol. Toxicol., 2005, 45, 291-310.
68. Koop, D.R. Hydroxylation of p-nitrophenol by rabbit ethanol-inducible cytochrome P-450 isozyme 3a. Mol. Pharmacol., 1986, 29, 399-404.
69. Collom, S.L.; Laddusaw, R.M.; Burch, A.M.; Kuzmic, P.; Perry, M.D., Jr; Miller, G.P. CYP2E1 substrate inhibition: mechanistic interpretation through an effector site for monocyclic compounds. J. Biol. Chem., 2008, 283, 3487-3496.
70. Hargreaves, M.B.; Jones, B.C.; Smith, C.A.; Gescher, A. Inhibi-tion of p-nitrophenol hydroxylase in rat liver microsomes by small aromatic and heterocyclic molecules. Drug Metab. Dis., 1994, 22, 806-810.
71. Harrelson, J.P.; Atkins, W.M.; Nelson, S.D. Multiple-ligand bind-ing in CYP2A6: probing mechanisms of cytochrome P450 coop-erativity by assessing substrate dynamics. Biochemistry, 2008, 47, 2978-2988.
72. Wang, J.F.; Wei, D.Q.; Wang, C.Y.; Ye, Y.; Li, Y.X.; Luo, Y.; Wang, W.W.; Liu, L.Z.; Zhao, Y.F. A theoretical study on the mechanism of 2:1 1,3 dipolar cycloaddition reactions. J. Theor. Comput. Chem., 2007, 6, 861-867.
73. Zhang, H.; Qin, F.; Ye, W.; Li, Z.; Ma, S.; Xia, Y.; Jiang, Y.; Zhu, J.; Li, Y.; Zhang, J.; Chen, H.F. Revealing the drug-resistant mechanism for diarylpyrimidine analogue inhibitors of HIV-1 re-verse transcriptase. Chem. Biol. Drug Des., 2011, 78, 427-437.
74. Wang, J.F.; Wei, D.Q.; Lin, Y.; Wang, Y.H.; Du, H.L.; Li, Y.X.; Chou, K.C. Insights from modeling the 3D structure of NAD(P)H-dependent D-xylose reductase of Pichia stipitis and its binding in-teractions with NAD and NADP. Biochem. Biophys. Res. Com-mun., 2007, 359, 323-329.
75. Zeng, Q.K.; Du, H.L.; Wang, J.F.; Wei, D.Q.; Wang, X.N.; Li, Y.X.; Lin, Y. Reversal of coenzyme specificity and improvement of catalytic efficiency of Pichia stipitis xylose reductase by rational site-directed mutagenesis. Biotechnol. Lett., 2009, 31, 1025-1029.
76. Wang, J.F.; Gong, K.; Wei, D.Q.; Li, Y.X.; Chou, K.C. Molecular dynamics studies on the interactions of PTP1B with inhibitors: from the first phosphate-binding site to the second one. Protein Eng. Des. Sel., 2009, 22, 349-355.
77. Li, Z.; Zhang, H.; Li, Y.; Zhang, J.; Chen, H.F. Drug resistant mechanism of diaryltriazine analog inhibitors of HIV-1 reverse transcriptase using molecular dynamics simulation and 3D-QSAR. Chem. Biol. Drug Des., 2011, 77, 63-74.
78. Wang, J.F.; Wei, D.Q.; Chou, K.C. Insights from investigating the interactions of adamantane-based drugs with the M2 proton chan-nel from the H1N1 swine virus. Biochem. Biophys. Res. Commun., 2009, 388, 413-417.
79. Qin, F.; Chen, Y.; Wu, M.; Li, Y.; Zhang, J.; Chen, H.F. Induced fit or conformational selection for RNA/U1A folding. RNA, 2010, 16, 1053-1061.
80. Wang, J.F.; Gong, K.; Wei, D.Q.; Li, Y.X. Structural flexibility and interactions of PTP1B's S-loop. Interdiscip. Sci., 2009, 1, 214-219.
81. Chen, Y.; He, Y.J.; Wu, M.; Yan, G.; Li, Y.; Zhang, J.; Chen, H.F. Insight into the stability of cross-beta amyloid fibril from molecu-lar dynamics simulation. Biopolymers, 2010, 93, 578-586.
82. Wang, J.F.; Chou, K.C. Insight into the molecular switch mecha-nism of human Rab5a from molecular dynamics simulations. Bio-chem. Biophys. Res. Commun., 2009, 390, 608-612.
83. Wang, J.F.; Chou, K.C. Insights into the mutation-induced HHH syndrome from modeling human mitochondrial ornithine trans-porter-1. PLoS One, 2012, 7, e31048.
84. Wang, Y.; Wei, D.Q.; Wang, J.F. Molecular dynamics studies on T1 lipase: insight into a double-flap mechanism. J. Chem. Inf. Model., 2010, 50, 875-878.
85. Wang, J.F.; Chou, K.C. Insights from studying the mutation-induced allostery in the M2 proton channel by molecular dynam-ics. Protein Eng. Des. Sel., 2010, 23, 663-666.
86. Qin, F.; Chen, Y.; Li, Y.X.; Chen, H.F. Induced fit for mRNA/TIS11d complex. J. Chem. Phys., 2009, 131, 115103.
87. Wang, J.F.; Chou, K.C. Insights from modeling the 3D structure of New Delhi metallo-ß-lactamse and its binding interactions with an-tibiotic drugs. PLoS One, 2011, 6, e18414.
88. Lian, P.; Wei, D.Q.; Wang, J.F.; Chou, K.C. An allosteric mecha-nism inferred from molecular dynamics simulations on phospho-lamban pentamer in lipid membranes. PLoS One, 2011, 6, e18587.
89. Wang, J.F.; Hao, P.; Li, Y.X.; Dai, J.L.; Li, X. Exploration of conformational transition in the aryl-binding site of human FXa us-ing molecular dynamics. J. Mol. Model., 2011, doi 10.1007/s00894-011-1295-x.
90. Chen, H.F. Molecular dynamics simulation of phosphorylated KID post-translational modification. PLoS One, 2009, 4, e6516.
91. Spatzenegger, M.; Liu, H.; Wang, Q.; Debarber, A.; Koop, D. R.; Halpert, J. R., Analysis of differential substrate selectivities of CYP2B6 and CYP2E1 by site-directed mutagenesis and molecular modeling. J. Pharmacol. Exp. Ther., 2003, 304, 477-87.
92. Li, J.; Wei, D.Q.; Wang, J.F.; Li, Y.X. A negative cooperativity mechanism of human CYP2E1 inferred from molecular dynamics simulations and free energy calculations. J. Chem. Inf. Model., 2011, doi 10.1021/ci2004016.
93. Blobaum, A.L.; Kent, U.M.; Alworth, W.L.; Hollengerg, P.F. Novel reversible inactivation of cytochrome P450 2E1 T303A by tert-butylacelene: the role of threonine 303 in proton delivery to the active site of cytochrome P450 2E1. J. Pharmacol. Exp. Ther., 2004, 310, 281-290.
94. Imai, M.; Shimada, H.; Watanabe, Y.; Matsushima-Hibiya, Y.; Makino, R.; Koga, H.; Horiuchi, T.; Ishimura, Y. Uncoupling of the cytochrome P-450cam monooxygenase reaction by a single mutation, threonine-252 to alanine or valine: possible role of the hydroxyl amino acid in oxygen activation. Proc. Natl. Acad. Sci. USA, 1989, 86, 7823-7827.
95. Vaz, A.D.; Pernecky, S.J.; Raner, G.M.; Coon, M.J. Peroxo-iron oxenoid-iron species as alternative oxygenating agents in cyto-chrome P450-catalyzed reactions: switching by threonine-302 to alanine mutagenesis of cytochrome P450 2B4. Proc. Natl. Acad. Sci. USA, 1996, 93, 4644-4648.
96. Vaz, A.D.; McGinnity, D.F.; Coon, M.J. Epoxidation of olefins by cytochrome P450: evidence from site-specific mutagenesis for hy-droperoxo-iron as an electrophilic oxidant. Proc. Natl. Acad. Sci. USA, 1998, 95, 3555-3560.
97. McGaughey, G.B.; Gagné, M.; Rappé, A.K. pi-Stacking interac-tions: Alive and well in proteins. J. Biol. Chem., 1998, 273, 15458-15463.
98. Burley, S.K.; Petsko, G.A. Aromatic-aromatic interaction: a mechanism of protein structure stabilization. Science, 1985, 229, 23-28.