Functional analysis of phenylalanine residues in the active site of cytochrome P450 2C9

Biochemistry

Volumn 47, Issue 45, 2008, Pages 11725-11734

  Mosher, Carrie M ^a   Hummel, Matthew A ^b   Tracy, Timothy S ^b   Rettie, Allan E ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

^b UNIVERSITY OF MINNESOTA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACIDS; BINDING ENERGY; BINDING SITES; BIOCHEMISTRY; FLOW INTERACTIONS; LIGANDS; METABOLISM; NUCLEAR MAGNETIC RESONANCE; PORPHYRINS; POWDERS; STOICHIOMETRY; SUBSTRATES;

ACTIVE SITES; BINDING MODES; CATALYTIC TURNOVERS; CYTOCHROME P450; DIFFERENTIAL INTERACTIONS; ENHANCED COUPLINGS; FLURBIPROFEN; HYDROXY METABOLITES; LIGAND BINDINGS; NONSTEROIDAL ANTIINFLAMMATORY DRUGS; PHENYLALANINE RESIDUES; PRODUCT FORMATIONS; RELAXATION STUDIES; SUBSTRATE BINDINGS; TO EFFECTS; TRYPTOPHAN MUTANTS;

DRUG PRODUCTS;

CYTOCHROME P450 2C9; DRUG METABOLITE; FLURBIPROFEN; LEUCINE; NONSTEROID ANTIINFLAMMATORY AGENT; PHENYLALANINE; TRYPTOPHAN; WARFARIN;

ARTICLE; CRYSTAL STRUCTURE; DRUG METABOLISM; ENZYME ACTIVE SITE; ENZYME MECHANISM; ENZYME SUBSTRATE COMPLEX; MUTATION; PRIORITY JOURNAL; PROTON NUCLEAR MAGNETIC RESONANCE; STEREOCHEMISTRY; WILD TYPE;

ARYL HYDROCARBON HYDROXYLASES; BINDING SITES; CATALYTIC DOMAIN; CHROMATOGRAPHY, LIQUID; FLURBIPROFEN; KINETICS; MAGNETIC RESONANCE SPECTROSCOPY; MUTAGENESIS, SITE-DIRECTED; PHENYLALANINE; PROTEIN BINDING; SPECTROMETRY, MASS, ELECTROSPRAY IONIZATION; SUBSTRATE SPECIFICITY; WARFARIN;

EID: 55849096976     PISSN: 00062960     EISSN: None     Source Type: Journal    
DOI: 10.1021/bi801231m     Document Type: Article

References (29)

1. Rettie, A. E., and Jones, J. P. (2005) Clinical and toxicological relevance of CYP2C9: drug-drug interactions and pharmacogenetics. Annu. Rev. Pharmacol. Toxicol. 45, 477-494.
2. Kirchheiner, J., and Brockmoller, J. (2005) Clinical consequences of cytochrome P450 2C9 polymorphisms. Clin. Pharmacol. Ther. 77, 1-16.
3. Wester, M. R., Yano, J. K., Schoch, G. A., Yang, C., Griffin, K. J., Stout, C. D., and Johnson, E. F. (2004) The structure of human cytochrome P450 2C9 complexed with flurbiprofen at 2.0-Å resolution. J. Biol. Chem. 279, 35630-35637.
4. Williams, P. A., Cosme, J., Ward, A., Angove, H. C., Matak Vinković, D., and Jhoti, H. (2003) Crystal structure of human cytochrome P450 2C9 with bound warfarin. Nature 424, 464-468.
5. Johnson, E. F., and Stout, C. D. (2005) Structural diversity of human xenobiotic-metabolizing cytochrome P450 monooxygenases. Biochem. Biophys. Res. Commun. 338, 331-336.
6. Haining, R. L., Jones, J. P., Henne, K. R., Fisher, M. B., Koop, D. R., Trager, W. F., and Rettie, A. E. (1999) Enzymatic determinants of the substrate specificity of CYP2C9: Role of B′-C loop residues in providing the π-stacking anchor site for warfarin binding. Biochemistry 38, 3285-3292.
7. Tracy, T. S., Hutzler, J. M., Haining, R. L., Rettie, A. E., Hummel, M. A., and Dickmann, L. J. (2002) Polymorphic variants (CYP2C9*3 and CYP2C9*5) and the F114L active site mutation of CYP2C9: Effect on atypical kinetic metabolism profiles. Drug Metab. Dispos. 30, 385-390.
8. Bush, E. D., Low, L. K., and Trager, W. F. (1983) A sensitive and specific stable isotope assay for warfarin and its metabolites. Biomed. Mass Spectrom. 10, 395-398.
9. Barnes, H. J., Arlotto, M. P., and Waterman, M. R. (1991) Expression and enzymatic activity of recombinant cytochrome P450 17α-hydroxylase in Escherichia coli. Proc. Natl. Acad. Sci. U.S.A. 88, 5597-5601.
10. 5 with cytochromes P4503A4 and P45017A: Relevance of heme transfer reactions. Biochemistry 40, 5018-5031.
11. Cheesman, M. J., Baer, B. R., Zheng, Y.-M., Gillam, E. M. J., and Rettie, A. E. (2003) Rabbit CYP4B1 engineered for high-level expression in Escherichia coli: Ligand stabilization and processing of the N-terminus and heme prosthetic group. Arch. Biochem. Biophys. 416, 17-24.
12. Estabrook, R. W., and Werringloer, J. (1978) The measurement of difference spectra: application to the cytochromes of microsomes. Methods Enzymol. 52, 212-220.
13. 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.
14. Hummel, M. A., Gannett, P. M., Aguilar, J. S., and Tracy, T. S. (2004) Effector-mediated alteration of substrate orientation in cytochrome P450 2C9. Biochemistry 43, 7207-7214.
15. Hummel, M. A., Gannett, P. M., Aguilar, J., and Tracy, T. S. (2008) Substrate proton to heme distances in CYP2C9 allelic variants and alterations by the heterotropic activator, dapsone. Arch. Biochem. Biophys. 475, 175-183.
16. 1) relaxation measurements. Arch. Biochem. Biophys. 384, 47-58.
17. Poli-Scaife, S., Attias, R., Dansette, P. M., and Mansuy, D. (1997) The substrate binding site of human liver cytochrome P450 2C9: An NMR study. Biochemistry 36, 12672-12682.
18. Gorsky, L. D., Koop, D. R., and Coon, M. J. (1984) On the stoichiometry of the oxidase and monooxygenase reactions catalyzed by liver microsomal cytochrome P-450. Products of oxygen reduction. J. Biol. Chem. 259, 6812-6817.
19. Ridderström, M., Masimirembwa, C., Trump-Kallmeyer, S., Ahlefelt, M., Otter, C., and Andersson, T. B. (2000) Arginines 97 and 108 in CYP2C9 are important determinants of the catalytic function. Biochem. Biophys. Res. Commun. 270, 983-987.
20. Melet, A., Assrir, N., Jean, P., Lopez-Garcia, M. P., Marques-Soares, C., Jaouen, M., Dansette, P. M., Sari, M. A., and Mansuy, D. (2003) Substrate selectivity of human cytochrome P450 2C9: importance of residues 476, 365, and 114 in recognition of diclofenac and sulfaphenazole and in mechanism-based inactivation by tienilic acid. Arch. Biochem. Biophys. 409, 80-91.
21. Rettie, A. E., Korzekwa, K. R., Kunze, K. L., Lawrence, R. F., Eddy, A. C., Aoyama, T., Gelboin, H. V., Gonzalez, F. J., and Trager, W. F. (1992) Hydroxylation of warfarin by human cDNA-expressed cytochrome P-450: a role for P-4502C9 in the etiology of (S)-warfarin-drug interactions. Chem. Res. Toxicol. 5, 54-59.
22. Hutzler, J. M., Wienkers, L. C., Wahlstrom, J. L., Carlson, T. J., and Tracy, T. S. (2003) Activation of cytochrome P450 2C9-mediated metabolism: mechanistic evidence in support of kinetic observations. Arch. Biochem. Biophys. 410, 16-24.
23. Hummel, M. A., Locuson, C. W., Gannett, P. M., Rock, D. A., Mosher, C. M., Rettie, A. E., and Tracy, T. S. (2005) CYP2C9 genotype-dependent effects on in vitro drug-drug interactions: switching of benzbromarone effect from inhibition to activation in the CYP2C9.3 variant. Mol. Pharmacol. 68, 644-651.
24. 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.
25. Rowland, P., Blaney, F. E., Smyth, M. G., Jones, J. J., Leydon, V. R., Oxbrow, A. K., Lewis, C. J., Tennant, M. G., Modi, S., Eggleston, D. S., Chenery, R. J., and Bridges, A. M. (2006) Crystal structure of human cytochrome P450 2D6. J. Biol. Chem. 281, 7614-7622.
26. Schoch, G. A., Yano, J. K., Wester, M. R., Griffin, K. J., Stout, C. D., and Johnson, E. F. (2004) Structure of human microsomal cytochrome P450 2C8. Evidence for a peripheral fatty acid binding site. J. Biol. Chem. 279, 9497-9503.
27. Mildvan, A. S., and Gupta, R. K. (1978) Nuclear relaxation measurements of the geometry of enzyme-bound substrates and analogs. Methods Enzymol 49, 322-359.
28. Loida, P. J., and Sligar, S. G. (1993) Molecular recognition in cytochrome P-450: mechanism for the control of uncoupling reactions. Biochemistry 32, 11530-11538.
29. Kumar, V., Wahlstrom, J. L., Rock, D. A., Warren, C. J., Gorman, L. A., and Tracy, T. S. (2006) CYP2C9 inhibition: impact of probe selection and pharmacogenetics on in vitro inhibition profiles. Drug Metab. Dispos. 34, 1966-1975.