Structural Analysis of CYP2R1 in Complex with Vitamin D3

Journal of Molecular Biology

Volumn 380, Issue 1, 2008, Pages 95-106

  Strushkevich, Natallia ^a,c   Usanov, Sergey A ^c   Plotnikov, Alexander N ^a,b   Jones, Glenville ^d   Park, Hee Won ^a,b  

^a UNIVERSITY OF TORONTO   (Canada)

^b UNIVERSITY OF TORONTO   (Canada)

^c INSTITUTE OF BIOORGANIC CHEMISTRY   (Belarus)

^d QUEEN S UNIVERSITY   (Canada)

Author keywords

human cytochrome P450; membrane protein; vitamin D 25 hydroxylase; vitamin D3; X ray crystallography

Indexed keywords

COLECALCIFEROL; CYTOCHROME P450; CYTOCHROME P450 2R1; HEMOPROTEIN; SECOSTEROID;

ARTICLE; BINDING SITE; CRYSTAL STRUCTURE; ENZYME CONFORMATION; ENZYME SPECIFICITY; ENZYME STRUCTURE; HYDROPHOBICITY; MOLECULAR BIOLOGY; PRIORITY JOURNAL; PROTEIN PURIFICATION; RICKETS; STEROID BINDING; SURFACE PROPERTY;

EID: 44649195596     PISSN: 00222836     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.jmb.2008.03.065     Document Type: Article

References (73)

1. Bouillon R., Okamura W.H., and Norman A.W. Structure-function relationships in the vitamin D endocrine system. Endocr. Rev. 16 (1995) 200-257
2. Jones G., Strugnell S.A., and DeLuca H.F. Current understanding of the molecular actions of vitamin D. Physiol. Rev. 78 (1998) 1193-1231
3. Deeb K.K., Trump D.L., and Johnson C.S. Vitamin D signalling pathways in cancer: potential for anticancer therapeutics. Nature Rev. Cancer 7 (2007) 684-700
4. Haddad J.G., Matsuoka L.Y., Hollis B.W., Hu Y.Z., and Wortsman J. Human plasma transport of vitamin D after its endogenous synthesis. J. Clin. Invest. 91 (1993) 2552-2555
5. Fu G.K., Lin D., Zhang M.Y., Bikle D.D., Shackleton C.H., Miller W.L., and Portale A.A. Cloning of human 25-hydroxyvitamin D-1 alpha-hydroxylase and mutations causing vitamin D-dependent rickets type 1. Mol. Endocrinol. 11 (1997) 1961-1970
6. St-Arnaud R., Messerlian S., Moir J.M., Omdahl J.L., and Glorieux F.H. The 25-hydroxyvitamin D 1-alpha-hydroxylase gene maps to the pseudovitamin D-deficiency rickets (PDDR) disease locus. J. Bone. Miner. Res. 12 (1997) 1552-1559
7. 3 whose mutation causes vitamin D-dependent rickets type 1. J. Biol. Chem. 280 (2005) 30511-30516
8. Wikvall K. Cytochrome P450 enzymes in the bioactivation of vitamin D to its hormonal form (review). Int. J. Mol. Med. 7 (2001) 201-209
9. Lin C.J., Dardis A., Wijesuriya S.D., Abdullah M.A., Casella S.J., and Miller W.L. Lack of mutations in CYP2D6 and CYP27 in patients with apparent deficiency of vitamin D 25-hydroxylase. Mol. Genet. Metab. 80 (2003) 469-472
10. Ohyama Y., and Yamasaki T. Eight cytochrome P450s catalyze vitamin D metabolism. Front. Biosci. 9 (2004) 3007-3018
11. Prosser D.E., and Jones G. Enzymes involved in the activation and inactivation of vitamin D. Trends. Biochem. Sci. 29 (2004) 664-673
12. Shinkyo R., Sakaki T., Kamakura M., Ohta M., and Inouye K. Metabolism of vitamin D by human microsomal CYP2R1. Biochem. Biophys. Res. Commun. 324 (2004) 451-457
13. Guo Y.D., Strugnell S., Back D.W., and Jones G. Transfected human liver cytochrome P-450 hydroxylates vitamin D analogs at different side-chain positions. Proc. Natl Acad. Sci. USA 90 (1993) 8668-8672
14. Cheng J.B., Motola D.L., Mangelsdorf D.J., and Russell D.W. De-orphanization of cytochrome P450 2R1: a microsomal vitamin D 25-hydroxilase. J. Biol. Chem. 278 (2003) 38084-38093
15. Cheng J.B., Levine M.A., Bell N.H., Mangelsdorf D.J., and Russell D.W. Genetic evidence that the human CYP2R1 enzyme is a key vitamin D 25-hydroxylase. Proc. Natl Acad. Sci. USA 101 (2004) 7711-7715
16. Choudhary D., Jansson I., Stoilov I., Sarfarazi M., and Schenkman J.B. Expression patterns of mouse and human CYP orthologs (families 1-4) during development and in different adult tissues. Arch. Biochem. Biophys. 436 (2005) 50-61
17. 3 and their biologic activity. J. Nutr. 99 (1969) 157-167
18. Bieche I., Narjoz C., Asselah T., Vacher S., Marcellin P., Lidereau R., et al. Reverse transcriptase-PCR quantification of mRNA levels from cytochrome (CYP)1, CYP2 and CYP3 families in 22 different human tissues. Pharmacogenet. Genomics 17 (2007) 731-742
19. Compston J.E. Hepatic osteodystrophy: vitamin D metabolism in patients with liver disease. Gut 27 (1986) 1073-1090
20. Johnson E.F., and Stout C.D. Structural diversity of human xenobiotic-metabolizing cytochrome P450 monooxygenases. Biochem. Biophys. Res. Commun. 338 (2005) 331-336
21. 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. 70 (2006) 120-128
22. Prosser D.E., Guo Y., Jia Z., and Jones G. Structural motif-based homology modeling of CYP27A1 and site-directed mutational analyses affecting vitamin D hydroxylation. Biophys. J. 90 (2006) 3389-3409
23. Annalora A.J., Bobrovnikov-Marjon E., Serda R., Pastuszyn A., Graham S.E., Marcus C.B., and 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. 460 (2007) 262-273
24. Masuda S., Prosser D.E., Guo Y.D., Kaufmann M., and Jones G. Generation of a homology model for the human cytochrome P450, CYP24A1, and the testing of putative substrate binding residues by site-directed mutagenesis and enzyme activity studies. Arch. Biochem. Biophys. 460 (2007) 177-191
25. 5 with cytochromes P4503A4 and P45017A: relevance of heme transfer reactions. Biochemistry 40 (2001) 5018-5031
26. Schoch G.A., Yano J.K., Wester M.R., Griffin K.J., Stout C.D., and Johnson E.F. Structure of human microsomal cytochrome P450 2C8. Evidence for a peripheral fatty acid binding site. J. Biol. Chem. 279 (2004) 9497-9503
27. Williams P.A., Cosme J., Ward A., Angove H.C., Matak Vinkovic D., and Jhoti H. Crystal structure of human cytochrome P450 2C9 with bound warfarin. Nature 424 (2003) 464-468
28. Williams 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 (2000) 121-131
29. Poulos T.L. Cytochrome P450 flexibility. Proc. Natl Acad. Sci. USA 100 (2003) 13121-13122
30. Poulos T.L., Finzel B.C., Gunsalus I.C., Wagner G.C., and Kraut J. The 2.6-Å crystal structure of Pseudomonas putida cytochrome P-450. J. Biol. Chem. 260 (1985) 16122-16130
31. Imai M., Shimada H., Watanabe Y., Matsushima-Hibiya Y., Makino R., Koga H., et al. Uncoupling of the cytochrome P-450cam monooxygenase reaction by a single mutation, threonine-252 to alanine or valine: possible role of the hydroxy amino acid in oxygen activation. Proc. Natl Acad. Sci. USA 86 (1989) 7823-7827
32. Cojocaru V., Winn P.J., and Wade R.C. The ins and outs of cytochrome P450s. Biochim. Biophys. Acta 1770 (2007) 390-401
33. Kleywegt G.J., and Jones T.A. Detection, delineation, measurement and display of cavities in macromolecular structures. Acta. Crystallogr. D 50 (1994) 178-185
34. 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. 267 (1992) 83-90
35. Wester M.R., Johnson E.F., Marques-Soares C., Dansette P.M., Mansuy D., and Stout C.D. Structure of a substrate complex of mammalian cytochrome P450 2C5 at 2.3 Å resolution: evidence for multiple substrate binding modes. Biochemistry 42 (2003) 6370-6379
36. Pikuleva I.A., Puchkaev A., and Bjorkhem I. Putative helix F contributes to regioselectivity of hydroxylation in mitochondrial cytochrome P450 27A1. Biochemistry 40 (2001) 7621-7629
37. Annalora A., 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. 425 (2004) 133-146
38. Rochel N., Wurtz J.M., Mitschler A., Klaholz B., and Moras D. The crystal structure of the nuclear receptor for vitamin D bound to its natural ligand. Mol. Cell 5 (2000) 173-179
39. Podust L.M., Yermalitskaya L.V., Lepesheva G.I., Podust V.N., Dalmasso E.A., and Waterman M.R. Estriol bound and ligand-free structures of sterol 14α-demethylase. Structure 12 (2004) 1937-1945
40. Lepesheva G.I., Zaitseva N.G., Nes W.D., Zhou W., Arase M., Liu J., et al. CYP51 from Trypanosoma cruzi: a phyla-specific residue in the B′ helix defines substrate preferences of sterol 14alpha-demethylase. J. Biol. Chem. 281 (2006) 3577-3585
41. Wester M.R., Yano J.K., Schoch G.A., Yang C., Griffin K.J., Stout C.D., and Johnson E.F. The structure of human cytochrome P450 2C9 complexed with flurbiprofen at 2.0-Å resolution. J. Biol. Chem. 279 (2004) 35630-35637
42. Hlavica P., Schulze J., and Lewis D.F. Functional interaction of cytochrome P450 with its redox partners: a critical assessment and update of the topology of predicted contact regions. J. Inorg. Biochem. 96 (2003) 279-297
43. 5 in catalysis by cytochrome P450 2B4. Biochem. Biophys. Res. Commun. 338 (2005) 499-506
44. Jones G., Byford V., West S., Masuda S., Ibrahim G., Kaufmann M., et al. Hepatic activation and inactivation of clinically-relevant vitamin D analogs and prodrugs. Anticancer Res. 26 (2006) 2589-2595
45. Oku K., Watanabe H., Kubota M., Fukuda S., Kurimoto M., Tsujisaka Y., et al. NMR and quantum chemical study on the OH...π and CH...O interactions between trehalose and unsaturated fatty acids: implication for the mechanism of antioxidant function of trehalose. J. Am. Chem. Soc. 125 (2003) 12739-12748
46. Norman A.W., Ishizuka S., and Okamura W.H. Ligands for the vitamin D endocrine system: different shapes function as agonists and antagonists for genomic and rapid response receptors or as a ligand for the plasma vitamin D binding protein. J. Steroid Biochem. Mol. Biol. 76 (2001) 49-59
47. Tocchini-Valentini G., Rochel N., Wurtz J.M., Mitschler A., and Moras D. Crystal structures of the vitamin D receptor complexed to superagonist 20-epi ligands. Proc. Natl Acad. Sci. USA 98 (2001) 5491-5496
48. 3 hormone analogues and a LXXLL-containing coactivator peptide. Biochemistry 43 (2004) 4101-4110
49. Rochel N., Hourai S., Perez-Garcia X., Rumbo A., Mourino A., and Moras D. Crystal structure of the vitamin D nuclear receptor ligand binding domain in complex with a locked side-chain analog of calcitriol. Arch. Biochem. Biophys. 460 (2007) 172-176
50. Verboven C., Rabijns A., De Maeyer M., Van Baelen H., Bouillon R., and De Ranter C. A structural basis for the unique binding features of the human vitamin D-binding protein. Nature Struct. Biol. 9 (2002) 131-136
51. Ozbek S., Engel J., and Stetefeld J. Storage function of cartilage oligomeric matrix protein: the crystal structure of the coiled-coil domain in complex with vitamin D(3). EMBO J. 21 (2002) 5960-5968
52. Couthon F., Clottes E., and Vial C. Refolding of SDS- and thermally denatured MM-creatine kinase using cyclodextrins. Biochem. Biophys. Res. Commun. 227 (1996) 854-860
53. Neufeld E.B., Cooney A.M., Pitha J., Dawidowicz E.A., Dwyer N.K., Pentchev P.G., and Blanchette-Mackie E.J. Intracellular trafficking of cholesterol monitored with a cyclodextrin. J. Biol. Chem. 271 (1996) 21604-21613
54. Rozema D., and Gellman S.H. Artificial chaperone-assisted refolding of carbonic anhydrase B. J. Biol. Chem. 271 (1996) 3478-3487
55. Challa R., Ahuja A., Ali J., and Khar R.K. Cyclodextrins in drug delivery: an updated review. AAPS Pharm. Sci. Tech. 6 (2005) E329-E357
56. Piel G., Piette M., Barillaro V., Castagne D., Evrard B., and Delattre L. Study of the relationship between lipid binding properties of cyclodextrins and their effect on the integrity of liposomes. Int. J. Pharm. 338 (2007) 35-42
57. Signorell G.A., Kaufmann T.C., Kukulski W., Engel A., and Remigy H.W. Controlled 2D crystallization of membrane proteins using methyl-β-cyclodextrin. J. Struct. Biol. 157 (2007) 321-328
58. 3: unique hydroxylated metabolites formed during catalysis with cytochrome P450scc (CYP11A1). Proc. Natl Acad. Sci. USA 100 (2003) 14754-14759
59. Lepesheva G.I., Nes W.D., Zhou W., Hill G.C., and Waterman M.R. CYP51 from Trypanosoma brucei is obtusifoliol-specific. Biochemistry 43 (2004) 10789-10799
60. Mast N., and Pikuleva I.A. A simple and rapid method to measure cholesterol binding to P450s and other proteins. J. Lipid. Res. 46 (2005) 1561-1568
61. Deng H., Wu J., So S.P., and Ruan K.H. Identification of the residues in the helix F/G loop important to catalytic function of membrane-bound prostacyclin synthase. Biochemistry 42 (2003) 5609-5617
62. Headlam M.J., Wilce M.C., and Tuckey R.C. The F-G loop region of cytochrome P450scc (CYP11A1) interacts with the phospholipid membrane. Biochim. Biophys. Acta 1617 (2003) 96-108
63. Izumi S., Kaneko H., Yamazaki T., Hirata T., and Kominami S. Membrane topology of guinea pig cytochrome P450 17 α revealed by a combination of chemical modifications and mass spectrometry. Biochemistry 42 (2003) 14663-14669
64. Meharenna Y.T., Li H., Hawkes D.B., Pearson A.G., De Voss J., and Poulos T.L. Crystal structure of P450cin in a complex with its substrate, 1,8-cineole, a close structural homologue to D-camphor, the substrate for P450cam. Biochemistry 43 (2004) 9487-9494
65. Ouellet H., Podust L.M., and de Montellano P.R. Mycobacterium tuberculosis CYP130: crystal structure, biophysical characterization, and interactions with antifungal azole drugs. J. Biol. Chem. 283 (2008) 5069-5080
66. von Wachenfeldt C., Richardson T.H., Cosme J., and Johnson E.F. Microsomal P450 2C3 is expressed as a soluble dimer in Escherichia coli following modification of its N-terminus. Arch. Biochem. Biophys. 339 (1997) 107-114
67. Otwinovski Z. Processing of X-ray diffraction data collection in oscillation mode. Methods Enzymol. 276 (1997) 307-326
68. Vagin A., and Teplyakov A. MOLREP: an automated program for molecular replacement. J. Appl. Crystallogr. 30 (1997) 1022-1025
69. Murshudov G.N., Vagin A.A., and Dodson E.J. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D 53 (1997) 240-255
70. Jones T.A., Zou J.Y., Cowan S.W., and Kjeldgaard M. Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr. A 47 (1991) 110-119
71. Omura T., and Sato R. The carbon monoxide-binding pigment of liver Microsomes. I. Evidence for its hemoprotein nature. J. Biol. Chem. 239 (1964) 2370-2378
72. 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 41 (2002) 8310-8320
73. Davis I.W., Murray L.W., Richardson J.S., and Richardson D.C. MOLPROBITY: structure validation and all-atom contact analysis for nucleic acids and their complexes. Nucleic Acids Res. 32 (2004) W615-W619