Crystal structure of CYP24A1, a mitochondrial cytochrome P450 involved in Vitamin D metabolism

Journal of Molecular Biology

Volumn 396, Issue 2, 2010, Pages 441-451

  Annalora, Andrew J ^a   Goodin, David B ^a   Hong, Wen Xu ^a   Zhang, Qinghai ^a   Johnson, Eric F ^a   Stout, C David ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

Adrenodoxin; Cytochrome P450; Mitochondria; Monotopic membrane protein; Vitamin D metabolism

Indexed keywords

ADRENODOXIN; CALCITRIOL; CYTOCHROME P450; CYTOCHROME P450 24A1; HEME; MEMBRANE PROTEIN; SECOSTEROID; UNCLASSIFIED DRUG; VITAMIN D; STEROID MONOOXYGENASE; VITAMIN D 24 HYDROXYLASE; VITAMIN D 24-HYDROXYLASE;

ARTICLE; CONTROLLED STUDY; CRYSTAL STRUCTURE; ENZYME ACTIVE SITE; ENZYME SUBSTRATE; ENZYME SUBSTRATE COMPLEX; GENETIC CONSERVATION; HYDROPHOBICITY; MITOCHONDRIAL MEMBRANE; MITOCHONDRION; MOLECULAR DOCKING; MOLECULAR RECOGNITION; NONHUMAN; PREDICTION; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN BINDING; PROTEIN STRUCTURE; RAT; VALIDATION PROCESS; VITAMIN D METABOLISM; AMINO ACID SEQUENCE; ANIMAL; BINDING SITE; CHEMICAL STRUCTURE; CHEMISTRY; ENZYMOLOGY; METABOLISM; MOLECULAR GENETICS; PROTEIN CONFORMATION; SEQUENCE HOMOLOGY; X RAY CRYSTALLOGRAPHY;

RATTUS;

AMINO ACID SEQUENCE; ANIMALS; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; CYTOCHROME P-450 ENZYME SYSTEM; MITOCHONDRIA; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; PROTEIN BINDING; PROTEIN CONFORMATION; RATS; SECOSTEROIDS; SEQUENCE HOMOLOGY, AMINO ACID; STEROID HYDROXYLASES; VITAMIN D;

EID: 77449094112     PISSN: 00222836     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jmb.2009.11.057     Document Type: Article

References (74)

1. Bernhardt R. Cytochromes P450 as versatile biocatalysts. J. Biotechnol. 2006, 124:128-145.
2. Sigel A., Sigel H., Sigel R. Metal Ions in Life Sciences, Vol. 3: The Ubiquitous Roles of Cytochrome P450 Proteins 2007, John Wiley and Sons, Ltd., Hoboken, NJ. A. Sigel, H. Sigel, R. Sigel (Eds.).
3. Nelson D.R. Metazoan cytochrome P450 evolution. Comp. Biochem. Physiol., Part C: Pharmacol., Toxicol. Endocrinol 1998, 121:15-22.
4. Guengerich F.P. Mechanisms of cytochrome P450 substrate oxidation: MiniReview. J. Biochem. Mol. Toxicol. 2007, 21:163-168.
5. Grinberg A.V., Hannemann F., Schiffler B., Müller J., Heinemann U., Bernhardt R. Adrenodoxin: structure, stability, and electron transfer properties. Proteins 2000, 40:590-612.
6. Pikuleva I.A., Tesh K., Waterman M.R., Kim Y. The tertiary structure of full-length bovine adrenodoxin suggests functional dimers. Arch. Biochem. Biophys. 2000, 373:44-55.
7. Behlke J., Ristau O., Müller E.C., Hannemann F., Bernhardt R. Self-association of adrenodoxin studied by using analytical ultracentrifugation. Biophys. Chem. 2007, 125:159-165.
8. Prosser D.E., Jones G. Enzymes involved in the activation and inactivation of vitamin D. Trends Biochem. Sci. 2004, 12:664-673.
9. Sakaki T., Kagawa N., Yamamoto K., Inouye K. Metabolism of vitamin D3 by cytochromes P450. Front. Biosci. 2005, 10:119-134.
10. Masuda S., Jones G. Promise of vitamin D analogues in the treatment of hyperproliferative conditions. Mol. Cancer Ther. 2006, 4:797-808.
11. Deeb K.K., Trump D.L., Johnson C.S. Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nat. Rev., Cancer 2007, 7:684-700.
12. Omdahl J.L., Morris H.A., May B.K. Hydroxylase enzymes of the vitamin D pathway: expression, function, and regulation. Annu. Rev. Nutr. 2002, 22:139-166.
13. Dusso A.S., Brown A.J., Slatopolsky E. Vitamin D. Am. J. Physiol. Renal Physiol. 2005, 289:8-28.
14. Holick M.F. The vitamin D deficiency pandemic and consequences for nonskeletal health: mechanisms of action. Mol. Aspects Med. 2008, 29:361-368.
15. Welsh J. Vitamin D and breast cancer: insights from animal models. Am. J. Clin. Nutr. 2004, 80:1721S-1724S.
16. Lou Y.R., Qiao S., Talonpoika R., Syvala H., Tuohimaa P. The role of vitamin D3 metabolism in prostate cancer. J. Steroid Biochem. Mol. Biol. 2004, 92:317-325.
17. Parise R.A., Egorin M.J., Kanterewicz B., Taimi M., Petkovich M., Lew A.M., et al. CYP24, the enzyme that catabolizes the antiproliferative agent vitamin D, is increased in lung cancer. Int. J. Cancer 2006, 119:1819-1828.
18. Pendás-Franco N., Aguilera O., Pereira F., González-Sancho J.M., Muñoz A. Vitamin D and Wnt/beta-catenin pathway in colon cancer: role and regulation of DICKKOPF genes. Anticancer Res. 2008, 28:2613-2623.
19. DeLuca H.F. Evolution of our understanding of vitamin D. Nutr. Rev. 2008, 66:S73-S87.
20. Sakaki T., Sawada N., Komai K., Shiozawa S., Yamada Y., Yamamoto K., et al. Dual metabolic pathway of 25-hydroxyvitamin D3 catalyzed by human CYP24. Eur. J. Biochem. 2000, 267:6158-6165.
21. Uskokovic M.R., Norman A.W., Manchand P.S., Studzinski G.P., Campbell M.J., Koeffler H.P., et al. Highly active analogs of 1alpha,25-dihydroxyvitamin D(3) that resist metabolism through C-24 oxidation and C-3 epimerization pathways. Steroids 2001, 66:463-471.
22. Schuster I., Egger H., Herzig G., Reddy G.S., Schmid J.A., Schüssler M., Vorisek G. Selective inhibitors of vitamin D metabolism-new concepts and perspectives. Anticancer Res. 2006, 26:2653-2668.
23. Hourai S., Rodrigues L.C., Antony P., Reina-San-Martin B., Ciesielski F., Magnier B.C., et al. Structure-based design of a superagonist ligand for the vitamin D nuclear receptor. Chem. Biol. 2008, 15:383-392.
24. Annalora A.J., Bobrovnikova-Marjon E., Serda R., Lansing L., Chiu M.L., Pastuszyn A., et al. Rat cytochrome P450C24 (CYP24A1) and the role of F249 in substrate binding and catalytic activity. Arch. Biochem. Biophys. 2004, 425:133-146.
25. Omdahl J.L., Swamy N., Serda R., Annalora A.J., Berne M., Ray R. Affinity labeling of rat cytochrome P450C24 (CYP24) and identification of Ser57 as an active site residue. J. Steroid Biochem. Mol. Biol. 2004, 89-90:159-162.
26. Annalora A.J., Bobrovnikov-Marjon E., Serda R., Pastuszyn A., Graham S.E., Marcus C.B., Omdahl J.L. Hybrid homology modeling and mutational analysis of cytochrome P450C24A1 (CYP24A1) of the vitamin D pathway: insights into substrate specificity and membrane bound structure-function. Arch. Biochem. Biophys. 2007, 460:262-273.
27. McCoy A.J., Grosse-Kunstleve R.W., Adams P.D., Winn M.D., Storoni L.C., Read R.J. Phaser crystallographic software. J. Appl. Crystallogr. 2007, 40:658-674.
28. Emsley P., Cowtan K. Coot: model-building tools for molecular graphics. Acta Crystallogr., Sect. D: Biol. Crystallogr. 2004, 60:2126-2132.
29. McRee D.E. XtalView/Xfit-a versatile program for manipulating atomic coordinates and electron density. J. Struct. Biol. 1999, 125:156-165.
30. The CCP4 suite: programs for protein crystallography. Acta Crystallogr., Sect. D: Biol. Crystallogr. 1994, 50:760-763. Collaborative Computational Project, Number 4.
31. Zhang Q., Ma X., Ward A., Hong W., Jaakola V., Stevens R.C. Designing facial amphiphiles for the stabilization of integral membrane proteins. Angew. Chem., Int. Ed. 2007, 46:7023-7025.
32. Soltis S.M., Cohen A.E., Deacon A., Eriksson T., González A., McPhillips S., et al. New paradigm for macromolecular crystallography experiments at SSRL: automated crystal screening and remote data collection. Acta Crystallogr., Sect. D: Biol. Crystallogr. 2008, 64:1210-1221.
33. Brunger A.T., Adams P.D., Clore G.M., DeLano W.L., Gros P., Grosse-Kunstleve R.W., et al. Crystallography & NMR system: a new software suite for macromolecular structure determination. Acta Crystallogr., Sect. D: Biol. Crystallogr. 1998, 54:905-921.
34. Yano J.K., Wester M.R., Schoch G.A., Griffin K.J., Stout C.D., Johnson E.F. The structure of human microsomal cytochrome P450 3A4 determined by X-ray crystallography to 2.05-Å resolution. J. Biol. Chem. 2004, 279:38091-38094.
35. Williams P.A., Cosme J., Vinkovic D.M., Ward A., Angove H.C., Day P.J., et al. Crystal structures of human cytochrome P450 3A4 bound to metyrapone and progesterone. Science 2004, 305:683-686.
36. Cojocaru V., Winn P.J., Wade R.C. The ins and outs of cytochrome P450s. Biochim. Biophys. Acta 2007, 1770:390-401.
37. Mast N., White M.A., Bjorkhem I., Johnson E.F., Stout C.D., Pikuleva I.A. Crystal structures of substrate-bound and substrate-free cytochrome P450 46A1, the principal cholesterol hydroxylase in the brain. Proc. Natl Acad. Sci. USA 2008, 105:9546-9551.
38. Strushkevich N., Usanov S.A., Plotnikov A.N., Jones G., Park H.W. Structural analysis of CYP2R1 in complex with vitamin D3. J. Mol. Biol. 2008, 380:95-106.
39. Claros M.G., von Heijne G. TopPred II: an improved software for membrane protein structure predictions. CABIOS, Comput. Appl. Biosci. 1994, 10:685-686.
40. Néron, B., Ménager, H., Maufrais, C., Joly, N., Tufféry, P., Letondal, C. & Maupetit, J. (2008). Mobyle: a new full web bioinformatics framework. Institut Pasteur (Logiciels et Banques de Données) and RPSB (Ressource Parisienne en Bioinformatique Structurale) http://mobyle.pasteur.fr/cgi-bin/MobylePortal/portal.py.
41. Engelman D.M., Steitz T.A., Goldman A. Identifying nonpolar transbilayer helices in amino acid sequences of membrane proteins. Annu. Rev. Biophys. Biophys. Chem. 1986, 15:321-353.
42. Williams P.A., Cosme J., Sridhar V., Johnson E.F., McRee D.E. Mammalian microsomal cytochrome P450 monooxygenase: structural adaptations for membrane binding and functional diversity. Mol. Cell 2000, 5:121-131.
43. Kemper B. Structural basis for the role in protein folding of conserved proline-rich regions in cytochromes P450. Toxicol. Appl. Pharmacol. 2004, 199:305-315.
44. Ozalp C., Szczesna-Skorupa E., Kemper B. Identification of membrane-contacting loops of the catalytic domain of cytochrome P450 2C2 by tryptophan fluorescence scanning. Biochemistry 2006, 45:4629-4637.
45. Pikuleva I.A., Mast N., Liao W.L., Turko I.V. Studies of membrane topology of mitochondrial cholesterol hydroxylases CYPs 27A1 and 11A1. Lipids 2008, 43:1127-1132.
46. Lomize M.A., Lomize A.L., Pogozheva I.D., Mosberg H.I. OPM: orientations of proteins in membranes database. Bioinformatics 2006, 22:623-625. http://opm.phar.umich.edu/.
47. White S.H. Membrane protein insertion: the biology-physics nexus. J. Gen. Physiol. 2007, 129:363-369.
48. Masuda S., Prosser D.E., Guo Y.D., Kaufmann M., Jones G. Generation of a homology model for the human cytochrome P450, CYP24A1, and the testing of putative substrate binding residues by site. Arch. Biochem. Biophys. 2007, 460:177-191.
49. Gomaa M.S., Simons C., Brancale A.J. Homology model of 1alpha,25-dihydroxyvitamin D3 24-hydroxylase cytochrome P450C24A1 (CYP24A1): active site architecture and ligand binding. J. Steroid Biochem. Mol. Biol. 2007, 104:53-60.
50. Hamamoto H., Kusudo T., Urushino N., Masuno H., Yamamoto K., Yamada S., et al. Structure-function analysis of vitamin D 24-hydroxylase (CYP24A1) by site-directed mutagenesis: amino acid residues responsible for species-based difference of CYP24A1 between humans and rats. Mol. Pharmacol. 2006, 70:120-128.
51. Prosser D.E., Kaufmann M., O'Leary B., Byford V., Jones G. Single A326G mutation converts human CYP24A1 from 25-OH-D3-24-hydroxylase into-23-hydroxylase, generating 1alpha,25-(OH)2D3-26,23-lactone. Proc. Natl Acad. Sci. USA 2007, 104:12673-12678.
52. Urushino N., Yamamoto K., Kagawa N., Ikushiro S., Kamakura M., Yamada S., et al. Interaction between mitochondrial CYP27B1 and adrenodoxin: role of arginine 458 of mouse CYP27B1. Biochemistry 2006, 45:4405-4412.
53. Usanov S.A., Graham S.E., Lepesheva G.I., Azeva T.N., Strushkevich N.V., Gilep A.A., et al. Probing the interaction of bovine cytochrome P450scc (CYP11A1) with adrenodoxin: evaluating site-directed mutations by molecular modeling. Biochemistry 2002, 41:8310-8320.
54. Beilke D., Weiss R., Löhr F., Pristovsek P., Hannemann F., Bernhardt R., Rüterjans H. A new electron transport mechanism in mitochondrial steroid hydroxylase systems based on structural changes upon the reduction of adrenodoxin. Biochemistry 2002, 41:7969-7978.
55. Heinz A., Hannemann F., Müller J.J., Heinemann U., Bernhardt R. The interaction domain of the redox protein adrenodoxin is mandatory for binding of the electron acceptor CYP11A1, but is not required for binding of the electron donor adrenodoxin reductase. Biochem. Biophys. Res. Commun. 2005, 338:491-498.
56. Gotoh O. Substrate recognition sites in cytochrome P450 family 2 (CYP2) proteins inferred from comparative analyses of amino acid and coding nucleotide sequences. J. Biol. Chem. 1992, 267:83-90.
57. Pikuleva I.A., Cao C., Waterman M.R. An additional electrostatic interaction between adrenodoxin and P450c27 (CYP27A1) results in tighter binding than between adrenodoxin and p450scc (CYP11A1). J. Biol. Chem. 1999, 274:2045-2052.
58. Bracey M.H., Cravatt B.F., Stevens R.C. Structural commonalities among integral membrane enzymes. FEBS Lett. 2004, 567:159-165.
59. Fowler P.W., Balali-Mood K., Deol S., Coveney P.V., Sansom M.S. Monotopic enzymes and lipid bilayers: a comparative study. Biochemistry 2007, 46:3108-3115.
60. Zhao Y., White M.A., Muralidhara B.K., Sun L., Halpert J.R., Stout C.D. Structure of microsomal cytochrome P450 2B4 complexed with the antifungal drug bifonazole: insight into P450 conformational plasticity and membrane interaction. J. Biol. Chem. 2006, 281:5973-5981.
61. Li H., Poulos T.L. The structure of the cytochrome p450BM-3 haem domain complexed with the fatty acid substrate, palmitoleic acid. Nat. Struct. Biol. 1997, 4:140-146.
62. Haines D.C., Chen B., Tomchick D.R., Bondlela M., Hegde A., Machius M., Peterson J.A. Crystal structure of inhibitor-bound P450BM-3 reveals open conformation of substrate access channel. Biochemistry 2008, 47:3662-3670.
63. Jaud S., Tobias T.J., Falke J.J., White S.H. Self-induced docking site of a deeply embedded peripheral membrane protein. Biophys. J. 2007, 92:517-524.
64. Kisselev P., Wessel R., Pisch S., Bornscheuer U., Schmid R.D., Schwarz D. Branched phosphatidylcholines stimulate activity of cytochrome P450SCC (CYP11A1) in phospholipid vesicles by enhancing cholesterol binding, membrane incorporation, and protein exchange. J. Biol. Chem. 1998, 273:1380-1386.
65. Murtazina D.A., Andersson U., Hahn I.S., Bjorkhem I., Ansari G.A., Pikuleva I.A. Phospholipids modify substrate binding and enzyme activity of human cytochrome P450 27A1. J. Lipid Res. 2004, 45:2345-2353.
66. Johnson E.F. Deciphering substrate recognition by drug-metabolizing cytochromes P450. Drug Metab. Dispos. 2003, 31:1532-1540.
67. Kuznetsov V.Y., Poulos T.L., Sevrioukova I.F. Putidaredoxin-to-cytochrome P450cam electron transfer: differences between the two reductive steps required for catalysis. Biochemistry 2006, 45:11934-11944.
68. Heinz A., Hannemann F., Müller J.J., Heinemann U., Bernhardt R. The interaction domain of the redox protein adrenodoxin is mandatory for binding of the electron acceptor CYP11A1, but is not required for binding of the electron donor adrenodoxin reductase. Biochem. Biophys. Res. Commun. 2005, 338:491-498.
69. Wester M.R., Stout C.D., Johnson E.F. Purification and crystallization of N-terminally truncated forms of microsomal cytochrome P450 2C5. Methods Enzymol. 2002, 357:73-79.
70. Goodsell D.S., Olson A.J. Automated docking of substrates to proteins by simulated annealing. Proteins: Struct., Funct., Genet. 1990, 8:195-202.
71. Goodsell D.S., Morris G.M., Olson A.J. Automated docking of flexible ligands: applications of AutoDock. J. Mol. Recognit. 1996, 9:1-5.
72. Morris G.M., Goodsell D.S., Halliday R.S., Huey R., Hart W.E., Belew R.K., Olson A.J. Automated docking using Lamarckian genetic algorithm and an empirical binding free energy function. J. Comp. Chem. 1998, 19:1639-1662.
73. Larkin M.A., Blackshields G., Brown N.P., Chenna R., McGettigan P.A., McWilliam H., et al. ClustalW2 and ClustalX version 2. Bioinformatics 2007, 23:2947-2948.
74. DeLano, W. L. The PyMOL Molecular Graphics System. DeLano Scientific LLC, San Carlos, CA, USA. http://www.pymol.org.