P450 active site modelling and mutagenesis

Last modified: Thu Sep 18 16:09:50 BST 2003

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• Fukuto, J.M., Brady, J.F., Burstyn, J.N., VanAtta, R.B., Valentine, J.S. and Cho, A.K. (1986) Direct formation of complexes between cytochrome P-450 and nitrosoarenes. Biochemistry 25, 2714-2719.
• Furuya, H., Shimizu, T., Hatano, M. and Fujii-Kuriyama, Y. (1989a) Mutations at the distal and proximal sites of cytochrome P-450d changed regio-specificity of acetanilide hydroxylations. Biochem. Biophys. Res. Commun. 160, 669-676.
• Furuya, H., Shimizu, T., Hirano, K., Hatano, M., Fujii-Kuriyama, Y., Raag, R. and Poulos, T.L. (1989b) Site-directed mutageneses of rat liver cytochrome P-450d: Catalytic activities toward benzphetamine and 7-ethoxycoumarin. Biochemistry 28, 6848-6857.
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• Graham-Lorence, S., Truan, G., Peterson, J.A., Falck, J.R., Wei, S., Helvig, C. and Capdevila, J.H. (1997) An active site substitution, F87V, converts cytochrome P450 BM-3 into a regio- and stereoselective (14S,15R)-arachidonic acid epoxygenase. J. Biol. Chem. 272, 1127-1135.
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• Hasler, J.A., Harlow, G.R., Szklarz, G.D., John, G.H., Kedzie, K.M., Burnett, V.L., He, Y.A., Kaminsky, L.S. and Halpert, J.R. (1994) Site-directed mutagenesis of putative substrate recognition sites in cytochrome P450 2B11: importance of amino acid residues 114, 290, and 363 for substrate specificity. Mol. Pharmacol. 46, 338-345.
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• He, Y.A., He, Y.Q., Szklarz, G.D. and Halpert, J.R. (1997) Identification of three key residues in substrate recognition site 5 of human cytochrome P450 3A4 by cassette and site-directed mutagenesis. Biochemistry 36, 8831-8839.
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• Hiroya, K., Shimizu, T., Hatano, M. and Fujii-Kuriyama, Y. (1991) Remarkable changes in catalytic activity toward testosterone of engineered cytochrome P-450d by mutations at putative distal site. Chem. Lett., 973-976.
• Hiroya, K., Ishigooka, M., Shimizu, T. and Hatano, M. (1992) Role of Glu318 and Thr319 in the catalytic function of cytochrome P450d (P4501A2): Effects of mutations on the methanol hydroxylation. FASEB J. 6, 749-751.
• Hiroya, K., Murakami, Y., Shimizu, T., Hatano, M. and Ortiz de Montellano, P.R. (1994) Differential roles of Glu318 and Thr319 in cytochrome P450 1A2 catalysis supported by NADPH-cytochrome P450 reductase and tert-butyl hydroperoxide. Arch. Biochem. Biophys. 310, 397-401.
• Imai, Y. and Nakamura, M. (1991) Nitrogenous ligation at the sixth coordination position of the Thr-301 to Lys-mutated P450IIC2 heme iron. J. Biochem. (Tokyo) 110, 884-888.
• Ishigooka, M., Shimizu, T., Hiroya, K. and Hatano, M. (1992) Role of Glu318 at the putative distal site in the catalytic function of cytochrome P450d. Biochemistry 31, 1528-1531.
• Ishimura, Y., Shimada, H., Kimata, Y. and Hirose, T. (1995) Site-directed mutants of cytochrome P450cam: role of THR252 in the catalysis. J. Inorg. Biochem. 59, 425.
• Iwasaki, M., Lindberg, R.L., Juvonen, R.O. and Negishi, M. (1993) Site-directed mutagenesis of mouse steroid 7-hydroxylase (cytochrome P-450₇): Role of residue-209 in determining steroid-cytochrome P-450 interaction. Biochem. J. 291, 569-573.
• Iwasaki, M., Darden, T.A., Pedersen, L.G. and Negishi, M. (1995) Altering the regiospecificity of androstenedione hydroxylase activity in P450s 2a-4/5 by a mutation of the residue at position 481. Biochemistry 34, 5054-5059.
• Jones, J.P., Shou, M. and Korzekwa, K.R. (1995) Stereospecific activation of the procarcinogen benzo[a]pyrene: a probe for the active sites of the cytochrome P450 superfamily. Biochemistry 34, 6956-6961.
• Jung, F., Griffin, K.J., Song, W., Richardson, T.H., Yang, M. and Johnson, E.F. (1998) Identification of amino acid substitutions that confer a high affinity for sulfaphenazole binding and a high catalytic efficiency for warfarin metabolism to P450 2C19. Biochemistry 37, 16270-16279.
• Juvonen, R.O., Iwasaki, M., Sueyoshi, T. and Negishi, M. (1993) Structural alteration of mouse P450coh by mutation of glycine-207 to proline: Spin equilibrium, enzyme kinetics, and heat sensitivity. Biochem. J. 294, 31-34.
• Kobayashi, Y., Fang, X., Szklarz, G.D. and Halpert, J.R. (1998) Probing the active site of cytochrome P450 2B1: Metabolism of 7-alkoxycoumarins by the wild type and five site-directed mutants. Biochemistry 37, 6679-6688.
• Koerts, J., Rietjens, I.M., Boersma, M.G. and Vervoort, J. (1995) ¹H NMR T₁ relaxation rate study on substrate orientation of fluoromethylanilines in the active sites of microsomal and purified cytochromes P450 1A1 and 2B1. FEBS Lett. 368, 279-284.
• Koley, A.P., Robinson, R.C. and Friedman, F.K. (1996) Cytochrome P450 conformation and substrate interactions as probed by CO binding kinetics. Biochimie 78, 706-713.
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• Krainev, A.G., Shimizu, T., Hiroya, K. and Hatano, M. (1992) Effects of mutations at Lys250, Arg251 and Lys253 of cytochrome P450 1A2 on the catalytic activities and the bindings of bifunctional axial ligands. Arch. Biochem. Biophys. 298, 198-203.
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• Lee-Robichaud, P., Akhtar, M.E. and Akhtar, M. (1998) An analysis of the role of active site protic residues of cytochrome P-450s: Mechanistic and mutational studies on 17-hydroxylase-17,20-lyase (P-450₁₇ also CYP17). Biochem. J. 330, 967-974.
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• Liu, J., He, Y.A. and Halpert, J.R. (1996) Role of residue 480 in substrate specificity of cytochrome P450 2B5 and 2B11. Arch. Biochem. Biophys. 327, 167-173.
• Luo, Z., He, Y.A. and Halpert, J.R. (1994) Role of residues 363 and 206 in conversion of cytochrome P450 2B1 from a steroid 16-hydroxylase to a 15-hydroxylase. Arch. Biochem. Biophys. 309, 52-57.
• Mancy, A., Broto, P., Dijols, S., Dansette, P.M. and Mansuy, D. (1995) The substrate binding site of human liver cytochrome P450 2C9: an approach using designed tienilic acid derivatives and molecular modeling. Biochemistry 34, 10365-10375.
• Mayuzumi, H., Sambongi, C., Hiroya, K., Shimizu, T., Tateishi, T. and Hatano, M. (1993) Effect of mutations of ionic amino acids of cytochrome P450 1A2 on catalytic activities toward 7-ethoxycoumarin and methanol. Biochemistry 32, 5622-5628.
• Nakano, R., Sato, H., Watanabe, A., Ito, O. and Shimizu, T. (1996) Conserved Glu³¹⁸ at the cytochrome P450 1A2 distal site is crucial in the nitric oxide complex stability. J. Biol. Chem. 271, 8570-8574.
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• Ortiz de Montellano, P.R. (1995) Arylhydrazines as probes of hemoprotein structure and function. Biochimie 77, 581-593.
• Paulsen, M.D., Filipovic, D., Sligar, S.G. and Ornstein, R.L. (1993) Controlling the regiospecificity and coupling of cytochrome P450cam: T185F mutant increases coupling and abolishes 3-hydroxynorcamphor product. Protein Science 2, 357-365.
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• Ramarao, M. and Kemper, B. (1995) Substitution at residue 473 confers progesterone 21-hydroxylase activity to cytochrome P450 2C2. Mol. Pharmacol. 48, 417-424.
• Richardson, T.H. and Johnson, E.F. (1994) Alterations of the regiospecificity of progesterone metabolism by the mutagenesis of two key amino acid residues in rabbit cytochrome P450 2C3v. J. Biol. Chem. 269, 23937-23943.
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• Shimizu, T., Sadeque, A.J.M., Hatano, M. and Fujii-Kuriyama, Y. (1989) Bindings of axial ligands to cytochrome P-450d mutants: A difference absorption spectral study. Biochim. Biophys. Acta 995, 116-121.
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• 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.
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• Stevens, J.C., Domanski, T.L., Harlow, G.R., White, R.B., Orton, E. and Halpert, J.R. (1999) Use of the steroid derivative RPR 106541 in combination with site-directed mutagenesis for enhanced cytochrome P-450 3A4 structure/function analysis. J. Pharmacol. Exp. Ther. 290, 594-602.
• Straub, P., Ramarao, M.K. and Kemper, B. (1993) Preference for aromatic substitutions at tryptophan-120, which is highly conserved and a potential mediator of electron transfer in cytochrome P450 2C2. Biochem. Biophys. Res. Commun. 197, 433-439.
• Strobel, S.M. and Halpert, J.R. (1997) Reassessment of cytochrome P450 2B2: Catalytic specificity and identification of four active site residues. Biochemistry 36, 11697-11706.
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• Szklarz, G.D., Ornstein, R.L. and Halpert, J.R. (1994) Application of 3-dimensional homology modeling of cytochrome P450 2B1 for interpretation of site-directed mutagenesis results. J. Biomol. Struct. Dyn. 12, 61-78.
• Szklarz, G.D., He, Y.-A. and Halpert, J.R. (1995) Site-directed mutagenesis as a tool for molecular modeling of cytochrome P450 2B1. Biochemistry 34, 14312-14322.
• Szklarz, G.D., He, Y.Q., Kedzie, K.M., Halpert, J.R. and Burnett, V.L. (1996) Elucidation of amino acid residues critical for unique activities of rabbit cytochrome P450 2B5 using hybrid enzymes and reciprocal site-directed mutagenesis with rabbit cytochrome P450 2B4. Arch. Biochem. Biophys. 327, 308-318
• Tsao, C.-C., Wester, M.R., Ghanayem, B., Coulter, S.J., Chanas, B., Johnson, E.F. and Goldstein, J.A. (2001) Identification of human CYP2C19 residues that confer S-mephenytoin 4'-hydroxylation activity to CYP2C9. Biochemistry 40, 1937-1944.
• Tuck, S.F., Hiroya, K., Shimizu, T., Hatano, M. and Ortiz de Montellano, P.R. (1993) The cytochrome P450 1A2 (CYP1A2) active site: Topology and pertubations caused by Glu-318 and Thr-319 mutations. Biochemistry 32, 2548-2553.
• Vanden Bossche, H., Koymans, L.M. and Moereels, H. (1995) P450 inhibitors of use in medical treatment: focus on mechanisms of action. Pharmac. Therapeutics 67, 79-100.
• Vatsis, K.P., Peng, H.-M. and Coon, M.J. (2002) Replacement of active-site cysteine-436 by serine converts cytochrome P450 2B4 into an NADPH oxidase with negligible monooxygenase activity. J. Inorg. Biochem. 91, 542-553.
• Vaz, A.D.N., Pernecky, S.J., Raner, G. and Coon, M.J. (1996) 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, 4644-4648.
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