Molecular basis for a functionally unique cytochrome P450IIB1 variant.
作者： K.M. Kedzie , C.A. Balfour , G.Y. Escobar , S.W. Grimm , Y.A. He
DOI: 10.1016/S0021-9258(18)54602-0
关键词:
摘要: Abstract Liver microsomes from phenobarbital-treated rats of four inbred strains expressing distinct allelic variants cytochrome P450IIB1 were analyzed. The Wistar Munich (WM) strain exhibited 5- to 10-fold lower androstenedione 16 beta-hydroxylase activity (a specific marker) than the Lewis, Kyoto, and Furth strains. in WM liver was refractory inactivation by N-(2-p-nitrophenethyl)chlorofluoroacetamide, a selective inactivator other three Purified P450IIB1-WM insensitive 5-fold beta-hydroxylase, testosterone 16-hydroxylase, 7-ethoxycoumarin deethylase activities but same benzphetamine demethylase slightly higher alpha-hydroxylase purified outbred Sprague-Dawley rats, which appears correspond form Lewis rats. stereoselectivity 16-hydroxylation catalyzed (16 beta-OH:16 alpha-OH = 1.4) is thus that 12-15) preparations described. A cDNA encoding cloned sequenced, revealing single amino acid substitution (Gly-478----Ala) compared with published sequence (Fujii-Kuriyama, Y., Mizukami, Kawajiri, K., Sogawa, Muramatsu, M. (1982) Proc. Natl. Acad. Sci. U. S. A. 79, 2793-2797). Heterologous expression confirmed striking difference metabolite profiles, strongly implicating involvement Ala-478 defining distinctive catalytic properties P450IIB1-WM.
elsevier.com
sci-hub.st 参考文章(51)
David J. Waxman, Interactions of hepatic cytochromes P-450 with steroid hormones. Regioselectivity and stereospecificity of steroid metabolism and hormonal regulation of rat P-450 enzyme expression. Biochemical Pharmacology. ,vol. 37, pp. 71- 84 ,(1988) , 10.1016/0006-2952(88)90756-3
J C Stevens, J Halpert, Selective inactivation of four rat liver microsomal androstenedione hydroxylases by chloramphenicol analogs Molecular Pharmacology. ,vol. 33, pp. 103- 110 ,(1988)
T Aoyama, K Korzekwa, K Nagata, M Adesnik, A Reiss, D P Lapenson, J Gillette, H V Gelboin, D J Waxman, F J Gonzalez, Sequence requirements for cytochrome P-450IIB1 catalytic activity. Alteration of the stereospecificity and regioselectivity of steroid hydroxylation by a simultaneous change of two hydrophobic amino acid residues to phenylalanine. Journal of Biological Chemistry. ,vol. 264, pp. 21327- 21333 ,(1989) , 10.1016/S0021-9258(19)30083-3
Tsuneo Omura, Ryo Sato, The Carbon Monoxide-binding Pigment of Liver Microsomes Journal of Biological Chemistry. ,vol. 239, pp. 2379- 2385 ,(1964) , 10.1016/S0021-9258(20)82245-5
T Kronbach, E F Johnson, An inhibitory monoclonal antibody binds in close proximity to a determinant for substrate binding in cytochrome P450IIC5. Journal of Biological Chemistry. ,vol. 266, pp. 6215- 6220 ,(1991) , 10.1016/S0021-9258(18)38106-7
J R Halpert, N E Miller, L D Gorsky, On the mechanism of the inactivation of the major phenobarbital-inducible isozyme of rat liver cytochrome P-450 by chloramphenicol. Journal of Biological Chemistry. ,vol. 260, pp. 8397- 8403 ,(1985) , 10.1016/S0021-9258(17)39487-5
D J Waxman, A Ko, C Walsh, Regioselectivity and stereoselectivity of androgen hydroxylations catalyzed by cytochrome P-450 isozymes purified from phenobarbital-induced rat liver. Journal of Biological Chemistry. ,vol. 258, pp. 11937- 11947 ,(1983) , 10.1016/S0021-9258(17)44323-7
E Matsunaga, T Zeugin, U M Zanger, T Aoyama, U A Meyer, F J Gonzalez, Sequence requirements for cytochrome P-450IID1 catalytic activity. A single amino acid change (Ile380 Phe) specifically decreases Vmax of the enzyme for bufuralol but not debrisoquine hydroxylation. Journal of Biological Chemistry. ,vol. 265, pp. 17197- 17201 ,(1990) , 10.1016/S0021-9258(17)44888-5
A. Lewis Farr, Oliver H. Lowry, Rose J. Randall, Nira J. Rosebrough, Protein Measurement with the Folin Phenol Reagent Journal of Biological Chemistry. ,vol. 193, pp. 265- 275 ,(1951)
T. Nash, The colorimetric estimation of formaldehyde by means of the Hantzsch reaction Biochemical Journal. ,vol. 55, pp. 416- 421 ,(1953) , 10.1042/BJ0550416