A comparison of substrate dynamics in human CYP2E1 and CYP2A6

Biochemical and Biophysical Research Communications

Volumn 352, Issue 4, 2007, Pages 843-849

  Harrelson, John P ^a   Henne, Kirk R ^b   Alonso, Darwin O V ^a   Nelson, Sidney D ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

^b AMGEN INC   (United States)

Author keywords

Allosterism; Cooperativity; CYP2A6; CYP2E1; Dynamics; Isotope effect; kH kD; P450; Xylene

Indexed keywords

2,6 DIMETHYLNAPHTHALENE; 4,4' DIMETHYLBIPHENYL; BIPHENYL DERIVATIVE; CYTOCHROME P450; CYTOCHROME P450 2A6; CYTOCHROME P450 2E1; DEUTERIUM; ISOTOPE; META XYLENE; METHYL GROUP; NAPHTHALENE DERIVATIVE; ORTHO XYLENE; PARA XYLENE;

ALLOSTERISM; ARTICLE; ENZYME SUBSTRATE; ISOTOPE LABELING; MOLECULAR DYNAMICS; MOLECULAR INTERACTION; OXIDATION; PRIORITY JOURNAL;

ARYL HYDROCARBON HYDROXYLASES; CATALYSIS; CYTOCHROME P-450 CYP2E1; HUMANS; MIXED FUNCTION OXYGENASES; MOLECULAR STRUCTURE; OXIDATION-REDUCTION; SUBSTRATE SPECIFICITY; XYLENES;

EID: 33845396215     PISSN: 0006291X     EISSN: 10902104     Source Type: Journal    
DOI: 10.1016/j.bbrc.2006.11.071     Document Type: Article

References (39)

1. Vaz A.D., Pernecky S.J., Raner G.M., and Coon M.J. Peroxo-iron and oxenoid-iron species as alternative oxygenating agents in cytochrome P450-catalyzed reactions: switching by threonine-302 to alanine mutagenesis of cytochrome P450 2B4. Proc. Natl. Acad. Sci. USA 93 (1996) 4644-4648
2. Spatzenegger M., Liu H., Wang Q., Debarber A., Koop D.R., and Halpert J.R. Analysis of differential substrate selectivities of CYP2B6 and CYP2E1 by site-directed mutagenesis and molecular modeling. J. Pharmacol. Exp. Ther. 304 (2003) 477-487
3. Khan K.K., He Y.Q., Domanski T.L., and Halpert J.R. Midazolam oxidation by cytochrome P450 3A4 and active-site mutants: an evaluation of multiple binding sites and of the metabolic pathway that leads to enzyme inactivation. Mol. Pharmacol. 61 (2002) 495-506
4. Domanski T.L., He Y.A., Harlow G.R., and Halpert J.R. Dual role of human cytochrome P450 3A4 residue Phe-304 in substrate specificity and cooperativity. J. Pharmacol. Exp. Ther. 293 (2000) 585-591
5. Williams P.A., Cosme J., Ward A., Angove H.C., Matak Vinkovic D., and Jhoti H. Crystal structure of human cytochrome P450 2C9 with bound warfarin. Nature 424 (2003) 464-468
6. Scott E.E., He Y.A., Wester M.R., White M.A., Chin C.C., Halpert J.R., Johnson E.F., and Stout C.D. An open conformation of mammalian cytochrome P450 2B4 at 1.6-Å resolution. Proc. Natl. Acad. Sci. USA 100 (2003) 13196-13201
7. Scott E.E., White M.A., He Y.A., Johnson E.F., Stout C.D., and Halpert J.R. Structure of mammalian cytochrome P450 2B4 complexed with 4-(4-chlorophenyl)imidazole at 1.9-Å resolution: insight into the range of P450 conformations and the coordination of redox partner binding. J. Biol. Chem. 279 (2004) 27294-27301
8. Smith S.V., Koley A.P., Dai R., Robinson R.C., Leong H., Markowitz A., and Friedman F.K. Conformational modulation of human cytochrome P450 2E1 by ethanol and other substrates: a CO flash photolysis study. Biochemistry 39 (2000) 5731-5737
9. Prasad S., Mazumdar S., and Mitra S. Binding of camphor to Pseudomonas putida cytochrome p450(cam): steady-state and picosecond time-resolved fluorescence studies. FEBS Lett. 477 (2000) 157-160
10. cam. Biochemistry 41 (2002) 14499-14508
11. Davydov D.R., Botchkareva A.E., Kumar S., He Y.Q., and Halpert J.R. An electrostatically driven conformational transition is involved in the mechanisms of substrate binding and cooperativity in cytochrome P450eryF. Biochemistry 43 (2004) 6475-6485
12. Jovanovic T., and McDermott A.E. Observation of ligand binding to cytochrome P450 BM-3 by means of solid-state NMR spectroscopy. J. Am. Chem. Soc. 127 (2005) 13816-13821
13. Lee H., Ortiz de Montellano P.R., and McDermott A.E. Deuterium magic angle spinning studies of substrates bound to cytochrome P450. Biochemistry 38 (1999) 10808-10813
14. Foster A.B., Jarman M., Stevens J.D., Thomas P., and Westwood J.H. Isotope effects in O- and N-demethylations mediated by rat liver microsomes: an application of direct insertion electron impact mass spectrometry. Chem. Biol. Interact. 9 (1974) 327-340
15. Hamberg M., and Bjorkhem I. Oxidation of fatty acids. I. Mechanism of microsomal 1- and 2-hydroxylation. J. Biol. Chem. 246 (1971) 7411-7416
16. Hjelmeland L.M., Aronow L., and Trudell J.R. Intramolecular determination of substituent effects in hydroxylations catalyzed by cytochrome P-450. Mol. Pharmacol. 13 (1977) 634-639
17. Nelson S.D., and Trager W.F. The use of deuterium isotope effects to probe the active site properties, mechanism of cytochrome P450-catalyzed reactions, and mechanisms of metabolically dependent toxicity. Drug Metab. Dispos. 31 (2003) 1481-1498
18. Iyer K.R., Jones J.P., Darbyshire J.F., and Trager W.F. Intramolecular isotope effects for benzylic hydroxylation of isomeric xylenes and 4,4′-dimethylbiphenyl by cytochrome P450: relationship between distance of methyl groups and masking of the intrinsic isotope effect. Biochemistry 36 (1997) 7136-7143
19. Korzekwa K.R., Trager W.F., and Gillette J.R. Theory for the observed isotope effects from enzymatic systems that form multiple products via branched reaction pathways: cytochrome P-450. Biochemistry 28 (1989) 9012-9018
20. Atkins W.M. Non-Michaelis-Menten kinetics in cytochrome P450-catalyzed reactions. Annu. Rev. Pharmacol. Toxicol. 45 (2005) 291-310
21. Henne K.R., Fisher M.B., Iyer K.R., Lang D.H., Trager W.F., and Rettie A.E. Active site characteristics of CYP4B1 probed with aromatic ligands. Biochemistry 40 (2001) 8597-8605
22. Chang T.K., Gonzalez F.J., and Waxman D.J. Evaluation of triacetyloleandomycin, alpha-naphthoflavone and diethyldithiocarbamate as selective chemical probes for inhibition of human cytochromes P450. Arch. Biochem. Biophys. 311 (1994) 437-442
23. Draper A.J., Madan A., and Parkinson A. Inhibition of coumarin 7-hydroxylase activity in human liver microsomes. Arch. Biochem. Biophys. 341 (1997) 47-61
24. Pelkonen O., Rautio A., Raunio H., and Pasanen M. CYP2A6: a human coumarin 7-hydroxylase. Toxicology 144 (2000) 139-147
25. Patten C.J., Ishizaki H., Aoyama T., Lee M., Ning S.M., Huang W., Gonzalez F.J., and Yang C.S. Catalytic properties of the human cytochrome P450 2E1 produced by cDNA expression in mammalian cells. Arch. Biochem. Biophys. 299 (1992) 163-171
26. Shimada T., Tsumura F., and Yamazaki H. Prediction of human liver microsomal oxidations of 7-ethoxycoumarin and chlorzoxazone with kinetic parameters of recombinant cytochrome P-450 enzymes. Drug Metab. Dispos. 27 (1999) 1274-1280
27. Spracklin D.K., Hankins D.C., Fisher J.M., Thummel K.E., and Kharasch E.D. Cytochrome P450 2E1 is the principal catalyst of human oxidative halothane metabolism in vitro. J. Pharmacol. Exp. Ther. 281 (1997) 400-411
28. Spracklin D.K., and Kharasch E.D. Human halothane reduction in vitro by cytochrome P450 2A6 and 3A4: identification of low and high KM isoforms. Drug Metab. Dispos. 26 (1998) 605-607
29. Yoo J.S., Ishizaki H., and Yang C.S. Roles of cytochrome P450IIE1 in the dealkylation and denitrosation of N-nitrosodimethylamine and N-nitrosodiethylamine in rat liver microsomes. Carcinogenesis 11 (1990) 2239-2243
30. Le Gal A., Dreano Y., Lucas D., and Berthou F. Diversity of selective environmental substrates for human cytochrome P450 2A6: alkoxyethers, nicotine, coumarin, N-nitrosodiethylamine, and N-nitrosobenzylmethylamine. Toxicol. Lett. 144 (2003) 77-91
31. Feierman D.E., and Cederbaum A.I. Inhibition of microsomal oxidation of ethanol by pyrazole and 4-methylpyrazole in vitro. Increased effectiveness after induction by pyrazole and 4-methylpyrazole. Biochem. J. 239 (1986) 671-677
32. Guengerich F.P., Kim D.H., and Iwasaki M. Role of human cytochrome P-450 IIE1 in the oxidation of many low molecular weight cancer suspects. Chem. Res. Toxicol. 4 (1991) 168-179
33. Chen W., Koenigs L.L., Thompson S.J., Peter R.M., Rettie A.E., Trager W.F., and Nelson S.D. Oxidation of acetaminophen to its toxic quinone imine and nontoxic catechol metabolites by baculovirus-expressed and purified human cytochromes P450 2E1 and 2A6. Chem. Res. Toxicol. 11 (1998) 295-301
34. Gillette J.R., Darbyshire J.F., and Sugiyama K. Theory for the observed isotope effects on the formation of multiple products by different kinetic mechanisms of cytochrome P450 enzymes. Biochemistry 33 (1994) 2927-2937
35. Darbyshire J.F., Gillette J.R., Nagata K., and Sugiyama K. Deuterium isotope effects on A-ring and D-ring metabolism of testosterone by CYP2C11: evidence for dissociation of activated enzyme-substrate complexes. Biochemistry 33 (1994) 2938-2944
36. Rock D.A., Boitano A.E., Wahlstrom J.L., Rock D.A., and Jones J.P. Use of kinetic isotope effects to delineate the role of phenylalanine 87 in P450(BM-3). Bioorg. Chem. 30 (2002) 107-118
37. Jones J.P., Korzekwa K.R., Rettie A.E., and Trager W.F. Isotopically sensitive branching and its effect on the observed intramolecular isotope effects in cytochrome P-450 catalyzed reactions: a new method for the estimation of intrinsic isotope effects. J. Am. Chem. Soc. 108 (1986) 7074-7078
38. Yano J.K., Hsu M.H., Griffin K.J., Stout C.D., and Johnson E.F. Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxsalen. Nat. Struct. Mol. Biol. 12 (2005) 822-823
39. Atkins W.M., and Sligar S.G. Metabolic switching in cytochrome P-450cam: deuterium isotope effects on regiospecificity and the monooxygenase/oxidase ratio. J. Am. Chem. Soc. 109 (1987) 3754-3760