Time-dependent inactivation of P450 3A4 by raloxifene: Identification of Cys239 as the site of apoprotein alkylation

Chemical Research in Toxicology

Volumn 20, Issue 6, 2007, Pages 954-964

  Baer, Brian R ^a   Wienkers, Larry C ^a   Rock, Dan A ^a  

^a AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETAMIDE DERIVATIVE; APOPROTEIN; CYSTEINE; CYTOCHROME P450 3A4; N(1 PYRENE)IODOACETAMIDE; PROTEINASE K; RALOXIFENE; UNCLASSIFIED DRUG;

ARTICLE; CONTROLLED STUDY; DRUG PROTEIN BINDING; DRUG STRUCTURE; ENZYME INACTIVATION; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; MOLECULAR WEIGHT; NONHUMAN;

ALKYLATING AGENTS; ALKYLATION; APOPROTEINS; BINDING SITES; CYSTEINE; CYTOCHROME P-450 ENZYME SYSTEM; ENDOPEPTIDASE K; ENZYME INHIBITORS; ESTROGEN ANTAGONISTS; GLUTATHIONE; IODOACETAMIDE; KINETICS; MIDAZOLAM; MOLECULAR STRUCTURE; QUINOLINES; RALOXIFENE; RECOMBINANT PROTEINS; SEQUENCE ANALYSIS, PROTEIN; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION; SPECTROPHOTOMETRY, ULTRAVIOLET; TIME FACTORS;

EID: 34447133553     PISSN: 0893228X     EISSN: None     Source Type: Journal    
DOI: 10.1021/tx700037e     Document Type: Article

References (17)

1. Kalgutkar, A. S., Gardner, I., Obach, R. S., Shaffer, C. L., Callegari, E., Henne, K. R., Mutlib, A. E., Dalvie, D. K., Lee, J. S., Nakai, Y., O'Donnell, J. P., Boer, J., and Harriman, S. P. (2005) A comprehensive listing of bioactivation pathways of organic functional groups. Curr. Drug Metab. 6, 161-225.
2. Monks, T. J., Lau, S. S., and Gillette, J. R. (1984) Diffusion of reactive metabolites out of hepatocytes: studies with bromobenzene. J. Pharmacol. Exp. Ther. 228, 393-399.
3. Zhou, S., Yung Chan, S., Cher Goh, B., Chan, E., Duan, W., Huang, M., and McLeod, H. L. (2005) Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs. Clin. Pharmacokinet. 44, 279-304.
4. Koenigs, L. L., Peter, R. M., Hunter, A. P., Haining, R. L., Rettie, A. E., Friedberg, T., Pritchard, M. P., Shou, M., Rushmore, T. H., and Trager, W. F. (1999) Electrospray ionization mass spectrometric analysis of intact cytochrome P450: identification of tienilic acid adducts to P450 2C9. Biochemistry 38, 2312-2319.
5. Lightning, L. K., Jones, J. P., Friedberg, T., Pritchard, M. P., Shou, M., Rushmore, T. H., and Trager, W. F. (2000) Mechanism-based inactivation of cytochrome P450 3A4 by L-754,394. Biochemistry 39, 4276-4287.
6. Chen, Q., Ngui, J. S., Doss, G. A., Wang, R. W., Cai, X., DiNinno, F. P., Blizzard, T. A., Hammond, M. L., Stearns, R. A., Evans, D. C., Baillie, T. A., and Tang, W. (2002) Cytochrome P450 3A4-mediated bioactivation of raloxifene: irreversible enzyme inhibition and thiol adduct formation. Chem. Res. Toxicol. 15, 907-914.
7. Yu, L., Liu, H., Li, W., Zhang, F., Luckie, C., van Breemen, R. B., Thatcher, G. R., and Bolton, J. L. (2004) Oxidation of raloxifene to quinoids: potential toxic pathways via a diquinone methide and o-quinones. Chem. Res. Toxicol. 17, 879-888.
8. Gillam, E. M., Baba, T., Kim, B. R., Ohmori, S., and Guengerich, F. P. (1993) Expression of modified human cytochrome P450 3A4 in Escherichia coli and purification and reconstitution of the enzyme. Arch. Biochem. Biophys. 305, 123-131.
9. Holmans, P. L., Shet, M. S., Martin-Wixtrom, C. A., Fisher, C. W., and Estabrook, R. W. (1994) The high-level expression in Escherichia coli of the membrane-bound form of human and rat cytochrome b5 and studies on their mechanism of function. Arch. Biochem. Biophys. 312, 554-565.
10. Rock, D., Rock, D., and Jones, J. P. (2001) Inexpensive purification of P450 reductase and other proteins using 2′,5′-adenosine diphosphate agarose affinity columns. Protein Expr. Purif. 22, 82-83.
11. 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.
12. Yano, J. K., Wester, M. R., Schoch, G. A., Griffin, K. J., Stout, C. D., and Johnson, E. F. (2004) The structure of human microsomal cytochrome P450 3A4 determined by X-ray crystallography to 2.05-A resolution. J. Biol. Chem. 279, 38091-38094.
13. Shou, M., Grogan, J., Mancewicz, J. A., Krausz, K. W., Gonzalez, F. J., Gelboin, H. V., and Korzekwa, K. R. (1994) Activation of CYP3A4: evidence for the simultaneous binding of two substrates in a cytochrome P450 active site. Biochemistry 33, 6450-6455.
14. Silvers, K. J., Chazinski, T., McManus, M. E., Bauer, S. L., Gonzalez, F. J., Gelboin, H. V., Maurel, P., and Howard, P. C. (1992) Cytochrome P-450 3A4 (nifedipine oxidase) is responsible for the C-oxidative metabolism of 1-nitropyrene in human liver microsomal samples. Cancer Res. 52, 6237-6243.
15. Schrag, M. L., and Wienkers, L. C. (2000) Topological alteration of the CYP3A4 active site by the divalent cation Mg(2+). Drug Metab. Dispos. 28, 1198-1201.
16. Manabe, S., Sassa, S., and Kappas, A. (1985) Hereditary tyrosinemia. Formation of succinylacetone-amino acid adducts. J. Exp. Med. 162, 1060-1074.
17. Liu, H., Liu, J., van Breemen, R. B., Thatcher, G. R., and Bolton, J. L. (2005) Bioactivation of the selective estrogen receptor modulator desmethylated arzoxifene to quinoids: 4′-fluoro substitution prevents quinoid formation. Chem. Res. Toxicol. 18, 162-173.