Alteration in Catalytic Properties of Human CYP2D6 Caused by Substitution of Glycine-42 with Arginine, Lysine and Glutamic Acid

Drug Metabolism and Pharmacokinetics

Volumn 18, Issue 1, 2003, Pages 79-85

  Tsuzuki, Daisuke ^a   Hichiya, Hiroyuki ^a   Okuda, Yukie ^a   Narimatsu, Shizuo ^a   Yamamoto, Shigeo ^b   Tamagake, Keietsu ^c   Shinoda, Sumio ^d  

^a Laboratories of1Health Chemistry   (Japan)

^b Biomolecular Sciences   (Japan)

^c Pharmaceutical Physical Chemistry   (Japan)

^d OKAYAMA UNIVERSITY   (Japan)

Author keywords

CYP2D6; debrisoquine; bunitrolol; glycine 42; site directed mutagenesis; yeast cell

Indexed keywords

EID: 2942554236     PISSN: 13474367     EISSN: 18800920     Source Type: Journal    
DOI: 10.2133/dmpk.18.79     Document Type: Article

References (17)

1. Gonzalez, F. J.: The CYP2D Subfamily. In: Ioannides C, editor. Cytochromes P450: Metabolic and Toxicological Aspects. CRC Press, Boca Raton, FL, 1996 pp. 183-210.
2. Oscarson, M.: The home page of the Human Cytochrome P450 (CYP) Allele Nomenclature Committee.
3. Meyer, U. A. and Zanger, U. M.: Molecular mechanisms of genetic polymorphisms of drug metabolism. Ann. Rev. Pharmacol. Toxicol., 37: 268-296 (1997).
4. Narimatsu, S., Gotoh, M., Masubuchi, Y., Horie, T., Ohmori, S., Kitada, M., Kageyama, K., Asaoka, K., Yamamoto, I. and Suzuki, T.: Stereoselectivity in bunitrolol 4-hydroxylation in liver microsomes from marmosets and Japanese monkeys. Biol. Pharm. Bull., 19: 1429-1433 (1996).
5. Narimatsu, S., Kato, R., Horie, T., Ono, S., Tsutsui, M., Yabusaki, Y., Ohmori, S., Kitada, M., Ichioka, T., Shimada, N., Kato, R. and Ishikawa, T.: Enantioselectivity of bunitrolol 4-hydroxylation is reversed by the change of an amino acid residue from valine to methionine at position 374 of cytochrome P450-2D6. Chirality, 11: 1-9 (1999).
6. Narimatsu, S., Kobayashi, N., Masubuchi, Y., Horie, T., Kakegawa, T., Kobayashi, H., Hardwick, J.P., Gonzalez, F.J., Shimada, N., Ohmori, S., Kitada, M., Asaoka, K., Kataoka, H., Yamamoto, S. and Satoh, T.: Species difference in enantioselectivity for the oxidation of propranolol by cytochrome P450 2D enzymes. Chemico-Biol. Interact., 127: 73-90 (2000).
7. Tsuzuki, D., Takemi, C., Yamamoto, S., Tamagake, K., Imaoka, S., Funae, Y., Kataoka, H., Shinoda, S. and Narimatsu, S.: Functional evaluation of cytochrome P450 2D6 with Gly42Arg substitution expressed in Saccharomyces cerevisiae. Pharmacogenetics, 11: 709-718 (2001).
8. Sakaki, T., Ariyoshi-Shibata, M., Yabusaki, Y. and Ohkawa, H.: Organella-targeted expression of rat liver cytochrome P450c27 in yeast. Genetically engineered alteration of mitochondrial P450 into a microsomal form creates a novel functional electron transport chain. J. Biol. Chem., 267: 16497-16502 (1992).
9. Wan, J., Imaoka, S., Chow, T., Hiroi, T., Yabusaki, Y. and Funae, Y.: Expression of four rat CYP2D isoforms in Saccharomyces cerevisiae and their catalytic specificity. Arch. Biochem. Biophys., 348: 383-390 (1997).
10. Omura, T. and Sato, R.: The carbon monoxide-binding pigment of liver microsomes. I. Evidence for its hemoprotein nature. J. Biol. Chem., 239: 2370-2378 (1964).
11. Guengerich, F. P., Wang, P. and Davidson, N. K.: Estimation of isozymes of microsomal cytochrome P-450 in rats, rabbits, and humans using immunochemical staining coupled with sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Biochemistry, 21: 1698-7106 (1982).
12. Phillips, A. H. and Langdon, R. G.: Hepatic triphosphopyridine nucleotide-cytochrome c reductase: isolation, characterization, and kinetic studies. J. Biol. Chem., 237: 2652-2660 (1962).
13. Lowry, O. H., Rosebrough, N. J., Farr, A. L. and Randall, R. J.: Protein measurement with the Folin phenol reagent. J. Biol. Chem., 193: 265-275 (1951).
14. Yamaoka, K., Tanigawara, Y., Nakagawa, T. and Uno, T.: A pharmacokinetic analysis program (MULTI) for microcomputer. J. Pharmacobiodyn., 4: 897-885 (1981).
15. Yamazaki, S., Sato, K., Suhara, K., Sakaguchi, M., Mihara, K. and Omura, T.: Importance of the proline-rich region following signal-anchor sequence in the formation of correct conformation of microsomal cytochrome P-450s. J. Biochem., 114: 652-657 (1993).
16. Wiiliams, P. A., Cosme, J., Sridhar, V., Johnson, E. F. and McRee, D. E.: Mammalian microsomal cytochrome P450 monooxygenase: structural adaptations for membrane binding and functional diversity. Mol. Cell, 5: 121-131 (2000).
17. Winn, P. J., Ludemann, S. K., Gauges, R., Lounnas, V. and Wade, R. C.: Comparison of the dynamics of substrate access channels in three cytochrome P450s reveals different opening mechanisms and a novel functional role for a buried arginine. Proc. Natl. Acad. Sci. USA, 99: 5361-5366 (2002).