The structure of microsomal cytochrome P450 2C5: A steroid and drug metabolizing enzyme

Endocrine Research

Volumn 28, Issue 4, 2002, Pages 435-441

  Johnson, Eric F ^a   Wester, Michael R ^a   Stout, C David ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOCHROME P450 2C; ISOENZYME; STEROID; STEROID 21 MONOOXYGENASE;

ADRENAL GLAND; CATALYSIS; CONFERENCE PAPER; DRUG METABOLISM; ENZYME ANALYSIS; ENZYME STRUCTURE; ENZYME SUBSTRATE; LIVER; MICROSOME; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; SOLVATION; STEROID METABOLISM; X RAY DIFFRACTION;

ANIMALS; CATALYSIS; CRYSTALLIZATION; CRYSTALLOGRAPHY; CRYSTALLOGRAPHY, X-RAY; CYTOCHROME P-450 ENZYME SYSTEM; HUMANS; MICROSOMES; PHARMACEUTICAL PREPARATIONS; PROTEIN FOLDING; PROTEIN STRUCTURE, SECONDARY; STEROID 21-HYDROXYLASE; STEROIDS;

EID: 0036936995     PISSN: 07435800     EISSN: None     Source Type: Journal    
DOI: 10.1081/ERC-120016820     Document Type: Conference Paper

References (18)

1. Williams, P.A.; Cosme, J.; Sridhar, V.; Johnson, E.E; McRee, D.E. The crystallographic structure of a mammalian microsomal cytochrome P450 monooxygenase: Structural adaptations for membrane binding and functional diversity. Mol. Cell. 2000, 5, 121-132.
2. Johnson, E.E; Finlayson, M.; Hujsak, C.M.; Pendurthi, U.R.; Tukey, R.H. Genetic contributions to the variation among rabbits of liver microsomal deoxycorticosterone synthesis. Arch. Biochem. Biophys. 1989, 273, 273-280.
3. Senciall, I.R.; Dey, A.C. Acidic steroid metabolites: Evidence for the excretion of C-21-carboxylic acid metabolites of progesterone in rabbit urine. J. Steroid. Biochem. 1976, 7, 125-129.
4. Schwab, G.E.; Johnson, E.F. Variation in hepatic microsomal cytochrome P-450 1 concentration among untreated rabbits alters the efficiency of estradiol hydroxylation. Arch. Biochem. Biophys. 1985, 237, 17-26.
5. 5 → 4 isomerase type activity. Proc. Natl. Acad. Sci. USA 1990, 87, 9756-9760.
6. Richardson, T.H.; Johnson, E.F. The Cytochrome P4502C Subfamily. In Cytochromes P450, Metabolic and Toxicological Aspects; Inonnides, C., Ed.; CRC Press, Inc.: Boca Raton, FL, USA, 1996.
7. Richardson, T.H.; Jung, E; Griffin, K.J.; Wester, M.; Raucy, J.L.; Kemper, B.; Bornheim, L.M.; Hassett, C.; Omiecinski, C.J.; Johnson, E.F. Universal approach to the expression of human and rabbit cytochrome P450s of the 2C subfamily in Escherichia coli. Arch. Biochem. Biophys. 1995, 323, 87-96.
8. Rendic, S. Summary of information on human CYP enzymes, human P450 metabolism data. Drug. Metab. Rev. 2002, 34, 83-448.
9. Fisslthaler, B.; Popp, R.; Kiss, L.; Potente, M.; Harder, D.R.; Fleming, I.; Busse, R. Cytochrome P450 2C is an EDHF synthase in coronary arteries. Nature 1999, 401, 493-497.
10. Peterson, J.A.; Graham-Lorence, S. Bacterial P450s, structural similarities and functional differences. In Cytochrome P450, Structure, Mechanism, and Biochemistry, 2nd Ed.; Ortiz de Montellano, P.R., Ed.; Plenum Press: New York, 1995; 151-180.
11. Von Wachenfeldt, C.; Johnson, E.F. Structures of eukaryotic cytochrome P450 enzymes. In Cytochrome P450, Structure, Mechanism, and Biochemistry, 2nd Ed.; Ortiz de Montellano, P.R., Ed.; Plenum Press: New York, 1995; 183-244.
12. Von Wachenfeldt, C.; Richardson, T.H.; Cosme, J.; Johnson, E.F. Microsomal P450 2C3 is expressed as a soluble dimer in Echerichia coli following modifications of its N-terminus. Arch. Biochem. Biophys. 1997, 339, 107-114.
13. Cosme, J.; Johnson, E.F. Engineering microsomal cytochrome P450 2C5 to be a soluble, monomeric enzyme. Mutations that alter aggregation, phospholipid dependence of catalysis, and membrane binding. J. Biol. Chem. 2000, 275, 2545-2553.
14. Wester, M.R.; Stout, C.D.; Johnson, E.F. Purification and crystallization of N-terminally truncated forms of microsomal cytochrome P450 2C5. Methods Enzymol, in press.
15. Shank-Retzlaff, M.L.; Raner, G.M.; Coon, M.J.; Sligar, S.G.; Membrane topology of cytochrome P450 2B4 in langmuir-blodgett monolayers. Arch. Biochem. Biophys. 1998, 359, 82-88.
16. Ohta, Y.; Kawato, S.; Tagashira, H.; Takemori, S.; Kominami, S. Dynamic structures of adrenocortical cytochrome P-450 in proteoliposomes and microsomes, protein rotation study. Biochemistry 1992, 31, 12680-12687.
17. Bayburt, T.H.; Sligar, S.G. Single-molecule height measurements on microsomal cytochrome P450 in nanometer-scale phospholipid bilayer disks. Proc. Natl. Acad. Sci. USA 2002, 99, 6725-6730.
18. Mancy, A.; Dijols, S.; Poli, S.; Guengerich, F.P.; Mansuy, D. Interaction of sulfaphenazole derivatives with human liver cytochromes P450 2C: Molecular origin of the specific inhibitory effects of sulfaphenazole on CYP 2C9 and consequences for the substrate binding site topology of CYP 2C9. Biochemistry 1996, 35, 16205-1621.