Allosteric modulation of substrate motion in cytochrome P450 3A4-mediated xylene oxidation

Biochemistry

Volumn 53, Issue 6, 2014, Pages 1018-1028

  Childers, W Kurtis ^a,b   Harrelson, John P ^a  

^a PACIFIC UNIVERSITY   (United States)

^b Pinnacle Health System   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALLOSTERIC REGULATION; CYTOCHROME P-450 CYP3A; DEUTERIUM; HUMANS; HYDROXYLATION; KINETICS; LIGANDS; PROTEIN CONFORMATION; XYLENES;

EID: 84894259483     PISSN: 00062960     EISSN: 15204995     Source Type: Journal    
DOI: 10.1021/bi401472p     Document Type: Article

References (72)

1. Guengerich, F. P. (2001) Common and uncommon cytochrome P450 reactions related to metabolism and chemical toxicity Chem. Res. Toxicol. 14, 611-650
2. Isin, E. M. and Guengerich, F. P. (2007) Complex reactions catalyzed by cytochrome P450 enzymes Biochim. Biophys. Acta 1770, 314-329
3. Yang, J., Atkins, W. M., Isoherranen, N., Paine, M. F., and Thummel, K. E. (2012) Evidence of CYP3A allosterism in vivo: Analysis of interaction between fluconazole and midazolam Clin. Pharmacol. Ther. 91, 442-449
4. Chen, W., Koenigs, L. L., Thompson, S. J., Peter, R. M., Rettie, A. E., Trager, W. F., and Nelson, S. D. (1998) 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, 295-301
5. Atkins, W. M. (2005) Non-Michaelis-Menten kinetics in cytochrome P450-catalyzed reactions Annu. Rev. Pharmacol. Toxicol. 45, 291-310
6. Huang, M. T., Chang, R. L., Fortner, J. G., and Conney, A. H. (1981) Studies on the mechanism of activation of microsomal benzo[a]pyrene hydroxylation by flavonoids J. Biol. Chem. 256, 6829-6836
7. Lasker, J. M., Huang, M. T., and Conney, A. H. (1982) In vivo activation of zoxazolamine metabolism by flavone Science 216, 1419-1421
8. Schwab, G. E., Raucy, J. L., and Johnson, E. F. (1988) Modulation of rabbit and human hepatic cytochrome P-450-catalyzed steroid hydroxylations by α-naphthoflavone Mol. Pharmacol. 33, 493-499
9. Denisov, I. G. and Sligar, S. G. (2012) A novel type of allosteric regulation: Functional cooperativity in monomeric proteins Arch. Biochem. Biophys. 519, 91-102
10. Stresser, D. M., Blanchard, A. P., Turner, S. D., Erve, J. C., Dandeneau, A. A., Miller, V. P., and Crespi, C. L. (2000) Substrate-dependent modulation of CYP3A4 catalytic activity: Analysis of 27 test compounds with four fluorometric substrates Drug Metab. Dispos. 28, 1440-1448
11. Jones, J. P. (2004) Metabolic menages a trois: What does it mean for drug design? Drug Discovery Today 9, 592
12. Tang, W., Stearns, R. A., Kwei, G. Y., Iliff, S. A., Miller, R. R., Egan, M. A., Yu, N. X., Dean, D. C., Kumar, S., Shou, M., Lin, J. H., and Baillie, T. A. (1999) Interaction of diclofenac and quinidine in monkeys: Stimulation of diclofenac metabolism J. Pharmacol. Exp. Ther. 291, 1068-1074
13. Blobaum, A. L., Bridges, T. M., Byers, F. W., Turlington, M., Mattmann, M., Morrison, R. D., Mackie, C., Lavreysen, H., Bartolome, J. M., Macdonald, G. J., Steckler, T., Jones, C. K., Niswender, C. M., Conn, P. J., Lindsley, C. W., Stauffer, S. R., and Daniels, J. S. (2013) Heterotropic Activation of the Midazolam Hydroxylase Activity of CYP3A by a Positive Allosteric Modulator of mGlu5: In Vitro to In Vivo Translation and Potential Impact on Clinically Relevant Drug-Drug Interactions Drug Metab. Dispos. 41, 2066-2075
14. Hutzler, J. M., Frye, R. F., Korzekwa, K. R., Branch, R. A., Huang, S. M., and Tracy, T. S. (2001) Minimal in vivo activation of CYP2C9-mediated flurbiprofen metabolism by dapsone Eur. J. Pharm. Sci. 14, 47-52
15. Egnell, A. C., Houston, B., and Boyer, S. (2003) In vivo CYP3A4 heteroactivation is a possible mechanism for the drug interaction between felbamate and carbamazepine J. Pharmacol. Exp. Ther. 305, 1251-1262
16. Wienkers, L. C. and Heath, T. G. (2005) Predicting in vivo drug interactions from in vitro drug discovery data Nat. Rev. Drug Discovery 4, 825-833
17. Houston, J. B. and Kenworthy, K. E. (2000) In vitro-in vivo scaling of CYP kinetic data not consistent with the classical Michaelis-Menten model Drug Metab. Dispos. 28, 246-254
18. Obach, R. S. (2012) Heterotropic effects on drug-metabolizing enzyme activities: In vitro curiosity emerges as a clinically meaningful phenomenon (perhaps?) Clin. Pharmacol. Ther. 91, 385-387
19. Davydov, D. R. (2011) Microsomal monooxygenase as a multienzyme system: The role of P450-P450 interactions Expert Opin. Drug Metab. Toxicol. 7, 543-558
20. Davydov, D. R. and Halpert, J. R. (2008) Allosteric P450 mechanisms: Multiple binding sites, multiple conformers or both? Expert Opin. Drug Metab. Toxicol. 4, 1523-1535
21. 2+ Drug Metab. Dispos. 28, 1198-1201
22. Reed, J. R., Cawley, G. F., and Backes, W. L. (2013) Interactions between cytochromes P450 2B4 (CYP2B4) and 1A2 (CYP1A2) lead to alterations in toluene disposition and P450 uncoupling Biochemistry 52, 4003-4013
23. Cupp-Vickery, J., Anderson, R., and Hatziris, Z. (2000) Crystal structures of ligand complexes of P450eryF exhibiting homotropic cooperativity Proc. Natl. Acad. Sci. U.S.A. 97, 3050-3055
24. Williams, P. A., Cosme, J., Vinkovic, D. M., Ward, A., Angove, H. C., Day, P. J., Vonrhein, C., Tickle, I. J., and Jhoti, H. (2004) Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone Science 305, 683-686
25. Davydov, D. R., Rumfeldt, J. A., Sineva, E. V., Fernando, H., Davydova, N. Y., and Halpert, J. R. (2012) Peripheral ligand-binding site in cytochrome P450 3A4 located with fluorescence resonance energy transfer (FRET) J. Biol. Chem. 287, 6797-6809
26. Skopalik, J., Anzenbacher, P., and Otyepka, M. (2008) Flexibility of human cytochromes P450: Molecular dynamics reveals differences between CYPs 3A4, 2C9, and 2A6, which correlate with their substrate preferences J. Phys. Chem. B 112, 8165-8173
27. Ekroos, M. and Sjogren, T. (2006) Structural basis for ligand promiscuity in cytochrome P450 3A4 Proc. Natl. Acad. Sci. U.S.A. 103, 13682-13687
28. Williams, P. A., Cosme, J., Ward, A., Angove, H. C., Matak Vinkovic, D., and Jhoti, H. (2003) Crystal structure of human cytochrome P450 2C9 with bound warfarin Nature 424, 464-468
29. Wilderman, P. R., Shah, M. B., Jang, H. H., Stout, C. D., and Halpert, J. R. (2013) Structural and thermodynamic basis of (+)-α-pinene binding to human cytochrome P450 2B6 J. Am. Chem. Soc. 135, 10433-10440
30. Brandman, R., Lampe, J. N., Brandman, Y., and de Montellano, P. R. (2011) Active-site residues move independently from the rest of the protein in a 200 ns molecular dynamics simulation of cytochrome P450 CYP119 Arch. Biochem. Biophys. 509, 127-132
31. 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. (2003) An open conformation of mammalian cytochrome P450 2B4 at 1.6-Å resolution Proc. Natl. Acad. Sci. U.S.A. 100, 13196-13201
32. Scott, E. E., White, M. A., He, Y. A., Johnson, E. F., Stout, C. D., and Halpert, J. R. (2004) 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, 27294-27301
33. Wilderman, P. R., Shah, M. B., Liu, T., Li, S., Hsu, S., Roberts, A. G., Goodlett, D. R., Zhang, Q., Woods, V. L., Jr., Stout, C. D., and Halpert, J. R. (2010) Plasticity of cytochrome P450 2B4 as investigated by hydrogen-deuterium exchange mass spectrometry and X-ray crystallography J. Biol. Chem. 285, 38602-38611
34. Lee, H., Ortiz de Montellano, P. R., and McDermott, A. E. (1999) Deuterium magic angle spinning studies of substrates bound to cytochrome P450 Biochemistry 38, 10808-10813
35. Isin, E. M. and Guengerich, F. P. (2006) Kinetics and thermodynamics of ligand binding by cytochrome P450 3A4 J. Biol. Chem. 281, 9127-9136
36. Isin, E. M. and Guengerich, F. P. (2007) Multiple sequential steps involved in the binding of inhibitors to cytochrome P450 3A4 J. Biol. Chem. 282, 6863-6874
37. Iyer, K. R., Jones, J. P., Darbyshire, J. F., and Trager, W. F. (1997) 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, 7136-7143
38. Henne, K. R., Fisher, M. B., Iyer, K. R., Lang, D. H., Trager, W. F., and Rettie, A. E. (2001) Active site characteristics of CYP4B1 probed with aromatic ligands Biochemistry 40, 8597-8605
39. Nelson, S. D. and Trager, W. F. (2003) 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, 1481-1498
40. Hjelmeland, L. M., Aronow, L., and Trudell, J. R. (1977) Intramolecular determination of substituent effects in hydroxylations catalyzed by cytochrome P-450 Mol. Pharmacol. 13, 634-639
41. Miwa, G. T., Garland, W. A., Hodshon, B. J., Lu, A. Y., and Northrop, D. B. (1980) Kinetic isotope effects in cytochrome P-450-catalyzed oxidation reactions. Intermolecular and intramolecular deuterium isotope effects during the N-demethylation of N,N-dimethylphentermine J. Biol. Chem. 255, 6049-6054
42. Gelb, M. H., Heimbrook, D. C., Malkonen, P., and Sligar, S. G. (1982) Stereochemistry and deuterium isotope effects in camphor hydroxylation by the cytochrome P450cam monoxygenase system Biochemistry 21, 370-377
43. Rock, D. A., Perkins, B. N., Wahlstrom, J., and Jones, J. P. (2003) A method for determining two substrates binding in the same active site of cytochrome P450BM3: An explanation of high energy omega product formation Arch. Biochem. Biophys. 416, 9-16
44. Harrelson, J. P., Atkins, W. M., and Nelson, S. D. (2008) Multiple-ligand binding in CYP2A6: Probing mechanisms of cytochrome P450 cooperativity by assessing substrate dynamics Biochemistry 47, 2978-2988
45. Hanzlik, R. P. and Ling, K. H. J. (1993) Active-site dynamics of xylene hydroxylation by cytochrome-P-450 as revealed by kinetic deuterium-isotope effects J. Am. Chem. Soc. 115, 9363-9370
46. Harrelson, J. P., Henne, K. R., Alonso, D. O., and Nelson, S. D. (2007) A comparison of substrate dynamics in human CYP2E1 and CYP2A6 Biochem. Biophys. Res. Commun. 352, 843-849
47. Rock, D. A., Boitano, A. E., Wahlstrom, J. L., and Jones, J. P. (2002) Use of kinetic isotope effects to delineate the role of phenylalanine 87 in P450(BM-3) Bioorg. Chem. 30, 107-118
48. Conner, K. P., Vennam, P., Woods, C. M., Krzyaniak, M. D., Bowman, M. K., and Atkins, W. M. (2012) 1,2,3-Triazole-heme interactions in cytochrome P450: Functionally competent triazole-water-heme complexes Biochemistry 51, 6441-6457
49. Woods, C. M., Fernandez, C., Kunze, K. L., and Atkins, W. M. (2011) Allosteric activation of cytochrome P450 3A4 by α-naphthoflavone: Branch point regulation revealed by isotope dilution analysis Biochemistry 50, 10041-10051
50. Guengerich, F. P., Sohl, C. D., and Chowdhury, G. (2011) Multi-step oxidations catalyzed by cytochrome P450 enzymes: Processive vs. distributive kinetics and the issue of carbonyl oxidation in chemical mechanisms Arch. Biochem. Biophys. 507, 126-134
51. Roberts, A. G., Campbell, A. P., and Atkins, W. M. (2005) The thermodynamic landscape of testosterone binding to cytochrome P450 3A4: Ligand binding and spin state Biochemistry 44, 1353-1366
52. Cameron, M. D., Wen, B., Roberts, A. G., Atkins, W. M., Campbell, A. P., and Nelson, S. D. (2007) Cooperative binding of acetaminophen and caffeine within the P450 3A4 active site Chem. Res. Toxicol. 20, 1434-1441
53. Ghose, A. K., Viswanadhan, V. N., and Wendoloski, J. J. (1999) A knowledge-based approach in designing combinatorial or medicinal chemistry libraries for drug discovery. 1. A qualitative and quantitative characterization of known drug databases ACS Comb. Sci. 1, 55-68
54. Ueng, Y. F., Kuwabara, T., Chun, Y. J., and Guengerich, F. P. (1997) Cooperativity in oxidations catalyzed by cytochrome P450 3A4 Biochemistry 36, 370-381
55. Khan, K. K., He, Y. Q., Domanski, T. L., and Halpert, J. R. (2002) 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, 495-506
56. Korzekwa, K. R., Krishnamachary, N., Shou, M., Ogai, A., Parise, R. A., Rettie, A. E., Gonzalez, F. J., and Tracy, T. S. (1998) Evaluation of atypical cytochrome P450 kinetics with two-substrate models: Evidence that multiple substrates can simultaneously bind to cytochrome P450 active sites Biochemistry 37, 4137-4147
57. Korzekwa, K. R., Trager, W. F., and Gillette, J. R. (1989) Theory for the observed isotope effects from enzymatic systems that form multiple products via branched reaction pathways: Cytochrome P-450 Biochemistry 28, 9012-9018
58. Harada, N., Miwa, G. T., Walsh, J. S., and Lu, A. Y. (1984) Kinetic isotope effects on cytochrome P-450-catalyzed oxidation reactions. Evidence for the irreversible formation of an activated oxygen intermediate of cytochrome P-448 J. Biol. Chem. 259, 3005-3010
59. Jones, J. P., Korzekwa, K. R., Rettie, A. E., and Trager, W. F. (1986) 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, 7074-7078
60. Ling, K. H. and Hanzlik, R. P. (1989) Deuterium isotope effects on toluene metabolism. Product release as a rate-limiting step in cytochrome P-450 catalysis Biochem. Biophys. Res. Commun. 160, 844-849
61. Hanzlik, R. P. and Ling, K. H. J. (1990) Active-site dynamics of toluene hydroxylation by cytochrome-P-450 J. Org. Chem. 55, 3992-3997
62. Jerina, D. M. and Daly, J. W. (1974) Arene oxides: A new aspect of drug metabolism Science 185, 573-582
63. Langman, J. M. (1994) Xylene: Its toxicity, measurement of exposure levels, absorption, metabolism and clearance Pathology 26, 301-309
64. Porubsky, P. R., Meneely, K. M., and Scott, E. E. (2008) 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. 283, 33698-33707
65. Yano, J. K., Hsu, M. H., Griffin, K. J., Stout, C. D., and Johnson, E. F. (2005) Structures of human microsomal cytochrome P450 2A6 complexed with coumarin and methoxsalen Nat. Struct. Mol. Biol. 12, 822-823
66. Atkins, W. M. and Sligar, S. G. (1987) Metabolic switching in cytochrome-P-450cam: Deuterium-isotope effects on regiospecificity and the monooxygenase oxidase ratio J. Am. Chem. Soc. 109, 3754-3760
67. Grinkova, Y. V., Denisov, I. G., McLean, M. A., and Sligar, S. G. (2013) Oxidase uncoupling in heme monooxygenases: Human cytochrome P450 CYP3A4 in Nanodiscs Biochem. Biophys. Res. Commun. 430, 1223-1227
68. Koley, A. P., Buters, J. T., Robinson, R. C., Markowitz, A., and Friedman, F. K. (1997) Differential mechanisms of cytochrome P450 inhibition and activation by α-naphthoflavone J. Biol. Chem. 272, 3149-3152
69. Reed, J. R., Connick, J. P., Cheng, D., Cawley, G. F., and Backes, W. L. (2012) Effect of homomeric P450-P450 complexes on P450 function Biochem. J. 446, 489-497
70. Harlow, G. R. and Halpert, J. R. (1998) Analysis of human cytochrome P450 3A4 cooperativity: Construction and characterization of a site-directed mutant that displays hyperbolic steroid hydroxylation kinetics Proc. Natl. Acad. Sci. U.S.A. 95, 6636-6641
71. Domanski, T. L., He, Y. A., Harlow, G. R., and Halpert, J. R. (2000) Dual role of human cytochrome P450 3A4 residue Phe-304 in substrate specificity and cooperativity J. Pharmacol. Exp. Ther. 293, 585-591
72. Domanski, T. L. and Halpert, J. R. (2001) Analysis of mammalian cytochrome P450 structure and function by site-directed mutagenesis Curr. Drug Metab. 2, 117-137