Homology modeling and substrate binding study of human CYP2C9 enzyme

Proteins: Structure, Function and Genetics

Volumn 37, Issue 2, 1999, Pages 176-190

  Payne, Vilia Ann ^a   Chang, Yan Tyng ^a   Loew, Gilda H ^a  

^a MOLECULAR RESEARCH INSTITUTE   (United States)

Author keywords

Alignment; Hydroxylation; Naproxen; P450; Phenytoin; Progesterone; Xenobiotic

Indexed keywords

CYTOCHROME P450; NAPROXEN; PHENYTOIN; PROGESTERONE;

ARTICLE; BINDING SITE; DRUG METABOLISM; DRUG PROTEIN BINDING; ENZYME SPECIFICITY; ENZYME SUBSTRATE COMPLEX; HUMAN; HYDROXYLATION; MOLECULAR DYNAMICS; MOLECULAR INTERACTION; MOLECULAR MODEL; PRIORITY JOURNAL; THREE DIMENSIONAL IMAGING;

NON-PROGRAMMATIC;

AMINO ACID SEQUENCE; ARYL HYDROCARBON HYDROXYLASES; BINDING SITES; CYTOCHROME P-450 ENZYME SYSTEM; HUMANS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; NAPROXEN; PHENYTOIN; PROGESTERONE; PROTEIN CONFORMATION; SEQUENCE HOMOLOGY, AMINO ACID; STEROID 16-ALPHA-HYDROXYLASE; STEROID HYDROXYLASES;

EID: 0032742735     PISSN: 08873585     EISSN: None     Source Type: Journal    
DOI: 10.1002/(SICI)1097-0134(19991101)37:2<176::AID-PROT4>3.0.CO;2-8     Document Type: Article

References (80)

1. Rendic S, Di Carlo FJ. Human cytochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers, and inhibitors. Drug Metab Rev 1997;29:413-580.
2. Nelson DR, Koymans L, Kamataki T, et al. P450 superfamily: update on new sequences, gene mapping, accession numbers and nomenclature. Pharmacogenetics 1996;6:1-42.
3. Pelkonen O, Breimer DD. Role of environmental factors in the pharmacokinetics of drugs: considerations with respect to animal models, P-450 enzymes, and probe drugs. In: Welling, PG, Balant LP, Editors. Handbook of experimental pharmacology: pharmacokinetics of drugs. New York: Springer-Verlag; 1994. p 289-332.
4. Smith DA, Jones BC. Speculations on the substrate structure-activity relationship (SSAR) of cytochrome P450 enzymes. Biochem Pharmacol 1992;44:2089-2098.
5. Rettie AE, Korzekwa KR, Kunze KL, et al. Hydroxylation of warfarin by human cDNA-expressed cytochrome P-450: a role for P-4502C9 in the etiology of (S)-warfarin-drug interactions. Chem Res Toxicol 1992;5:54-59.
6. Miners JO, Coulter S, Tukey RH, Veronese ME, Birkett DJ. Cytochromes P450, 1A2, and 2C9 are responsible for the human hepatic O-demethylation of R-and S-naproxen. Biochem Pharmacol 1996;51:1003-1008.
7. Bajpai M, Roskos LK, Shen DD, Levy RH. Roles of cytochrome P4502C9 and cytochrome P4502C19 in the stereoselective metabolism of phenytoin to its major metabolite. Drug Metab Dispos 1996;24:1401-1403.
8. Lasker JM, Wester MR, Aramsombatdee E, Raucy JL. Characterization of CYP2C19 and CYP2C9 from human liver: respective roles in microsomal tolbutamide, S-mephenytoin, and omeprazole hydroxylations. Arch Biochem Biophys 1998;353:16-28.
9. Yamazaki H, Shimada T. Progesterone and testosterone hydroxylation by cytochromes P450 2C19, 2C9, and 3A4 in human liver microsomes. Arch Biochem Biophys 1996;346:161-169.
10. Yun CH, Shimada T, Guengerich FP. Roles of human liver cytochrome P4502C and 3A enzymes in the 3-hydroxylation of benzo(a)pyrene. Cancer Res 1992;52:1868-1874.
11. Gautier JC, Lecoeur S, Cosme J, et al. Contribution of human cytochrome P450 to benzo[a]pyrene and benzo[a]pyrene-7,8-dihydrodiol metabolism, as predicted from heterologous expression in yeast. Pharmacogenetics 1996;6:489-499.
12. Rahman A, Korzekwa KR, Grogan J, Gonzalez FJ, Harris JW. Selective biotransformation of taxol to 6 alpha-hydroxytaxol by human cytochrome P450 2C8. Cancer Res 1994;54:5543-5546.
13. Kaminsky LS, de Morais SM, Faletto MB, Dunbar DA, Goldstein JA. Correlation of human cytochrome P4502C substrate specificities with primary structure: warfarin as a probe. Mol Pharmacol 1993;43:234-239.
14. Klekotka PA, Richardson TH, Johnson EF, Halpert JR. Inactivation of Escherichia coli-expressed rabbit cytochrome P-450 2C enzymes by 17 beta-substituted steroids. J Pharmacol Exp Ther 1995;274:1450-1455.
15. Miners JO, Rees DL, Valente L, Veronese ME, Birkett DJ. Human hepatic cytochrome P450 2C9 catalyzes the rate-limiting pathway of torsemide metabolism. J Pharmacol Exp Ther 1995;272:1076-1081.
16. Jean P, Lopez-Garcia P, Dansette P, Mansuy D, Goldstein JL. Oxidation of tienilic acid by human yeast-expressed cytochromes P-450 2C8, 2C9, 2C18 and 2C19: evidence that this drug is a mechanism-based inhibitor specific for cytochrome P-450 2C9. Eur J Biochem 1996;241:797-804.
17. Jones BC, Hawksworth G, Horne VA, et al. Putative active site template model for cytochrome P4502C9 (tolbutamide hydroxylase). Drug Metab Dispos 1996;24:260-266.
18. Mancy A, Dijols S, Poli S, Guengerich 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;35:16205-16212.
19. Miners JO, Birkett DJ. Use of tolbutamide as a substrate probe for human hepatic cytochrome P450 2C9. Methods Enzymol 1996;272: 139-145.
20. Jung F, Richardson TH, Raucy JL, Johnson EF. Diazepam metabolism by cDNA-expressed human 2C P450s: identification of P4502C18 and P4502C19 as low K(M) diazepam N-demethylases. Drug Metab Dispos 1997;25:133-139.
21. Monsarrat B, Royer I, Wright M, Cresteil T. Biotransformation of taxoids by human cytochromes P450: structure-activity relationship. Bull Cancer 1997;84:125-133.
22. Sarich T, Kalhorn T, Magee S, et al. The effect of omeprazole pretreatment on acetaminophen metabolism in rapid and slow metabolizers of S-mephenytoin. Clin Pharmacol Ther 1997;62: 21-28.
23. Mancy A, Broto P, Dijols S, Dansette PM, Mansuy D. The substrate binding site of human liver cytochrome P450 2C9: an approach using designed tienilic acid derivatives and molecular modeling. Biochemistry 1995;34:10365-10375.
24. Poli-Scaife S, Attias R, Dansette PM, Mansuy D. The substrate binding site of human liver cytochrome P450 2C9: an NMR study. Biochemistry 1997;36:12672-12682.
25. Veronese ME, Doecke CJ, Mackenzie PI, et al. Site-directed mutation studies of human liver cytochrome P-450 isoenzymes in the CYP2C subfamily. Biochem J 1993;289:533-538.
26. de Morais SM, Wilkinson GR, Blaisdell J, Nakamura K, Meyer UA, Goldstein JA. The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans. J Biol Chem 1994;269:15419-15422.
27. Richardson TH, Johnson EF. Alterations of the regiospecificity of progesterone metabolism by the mutagenesis of two key amino acid residues in rabbit cytochrome P450 2C3v. J Biol Chem 1994;269:23937-23943.
28. Straub P, Lloyd M, Johnson EF, Kemper B. Differential effects of mutations in substrate recognition site 1 of cytochrome P450 2C2 on lauric acid and progesterone hydroxylation. Biochemistry 1994;33:8029-8034.
29. Daniel HI, Edeki TI. Genetic polymorphism of S-mephenytoin 4'-hydroxylation. Psychopharmacol Bull 1996;32:219-230.
30. Sullivan-Klose TH, Ghanayem BI, Bell DA, et al. The role of the CYP2C9-Leu359 allelic variant in the tolbutamide polymorphism. Pharmacogenetics 1996;6:341-349.
31. Bhasker CR, Miners JO, Coulter S, Birkett DJ. Allelic and functional variability of cytochrome P4502C9. Pharmacogenetics 1997;7:51-58.
32. Chang TK, Yu L, Goldstein JA, Waxman DJ. Identification of the polymorphically expressed CYP2C19 and the wild-type CYP2C9-ILE359 allele as low-Km catalysts of cyclophosphamide and ifosfamide activation. Pharmacogenetics 1997;7:211-221.
33. Inoue K, Yamazaki H, Imiya K, Akasaka S, Guengerich FP, Shimada T. Relationship between CYP2C9 and 2C19 genotypes and tolbutamide methyl hydroxylation and S-mephenytoin 4′-hydroxylation activities in livers of Japanese and Caucasian populations. Pharmacogenetics 1997;7:103-113.
34. Jung F, Griffin KJ, Song W, Richardson TH, Yang M, Johnson EF. 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 1998;37: 16270-16279.
35. Yamazaki H, Inoue K, Chiba K, et al. Comparative studies on the catalytic roles of cytochrome P450 2C9 and its Cys-and Leu-variants in the oxidation of warfarin, flurbiprofen, and diclofenac by human liver microsomes. Biochem Pharmacol 1998;56:243-251.
36. Poulos TL, Finzel BC, Howard AJ. Crystal structure of substrate-free Pseudomonas putida cytochrome P-450. Biochemistry 1986; 25:5314-5322.
37. Hasemann CA, Ravichandran KG, Peterson JA, Deisenhofer J. Crystal structure and refinement of cytochrome P450terp at 2.3 Å resolution. J Mol Biol 1994;236:1169-1185.
38. Ravichandran KG, Boddupalli SS, Hasemann CA, Peterson JA, Deisenhofer J. Crystal structure of hemoprotein domain of P450BM-3, a prototype for microsomal P450's. Science 1993;261: 731-736.
39. Li H, Poulos TL. Modeling protein-substrate interactions in the heme domain of cytochrome P450BM-3. Acta Crystallogr D 1995; 51:21-32.
40. Cupp-Vickery JR, Poulos TL. Structure of cytochrome P450eryF involved in erythromycin biosynthesis. Nat Struct Biol 1995;2:144-153.
41. Smith AT, Du P, Loew GH. Homology modeling of horseradish peroxidase. NATO ASI Ser Ser C 1995;457:75-93.
42. Chang YT, Loew GH. Construction and evaluation of a three-dimensional structure of cytochrome P450choP enzyme (CYP105C1). Protein Eng 1996;9:755-766.
43. Chang YT, Stiffelman OB, Loew GH. Computer modeling of 3D structures of cytochrome P450s. Biochimie 1996;78:771-779.
44. Chang YT, Stiffelman OB, Vakser IA, Loew GH, Bridges A, Waskell L. Construction of a 3D model of cytochrome P450 2B4. Protein Eng 1997;10:119-129.
45. Chang YT, Loew GH. Homology modeling and substrate binding study of human CYP4A11 enzyme. Proteins 1999;34:403-415.
46. Tracy TS, Marra C, Wrighton SA, Gonzalez FJ, Korzekwa KR. Involvement of multiple cytochrome P450 isoforms in naproxen O-demethylation. Eur J Clin Pharmacol 1997;52:293-298.
47. Kubow S. Inhibition of phenytoin bioactivation and teratogenicity by dietary n-3 fatty acids in mice. Lipids 1992;27:721-728.
48. Sellers EM, Holloway MR. Drug kinetics and alcohol ingestion. Clin Pharmacokinet 1978;3:440-452.
49. Levy RH. Phenytoin: Biopharmacology. Adv Neurol 1980;27:315-321.
50. Kronbach T, Kemper B, Johnson EF. A hypervariable region of P450IIC5 confers progesterone 21-hydroxylase activity to P450IIC1. Biochemistry 1991;30:6097-6102.
51. Waxman DJ, Lapenson DP, Aoyama T, Gelboin HV, Gonzalez FJ, Korzekwa K. Steroid hormone hydroxylase specificities of eleven cDNA-expressed human cytochrome P450s. Arch Biochem Biophys 1991;290:160-166.
52. Katagiri M, Kagawa N, Waterman MR. The role of cytochrome b5 in the biosynthesis of androgens by human P450c17. Arch Biochem Biophys 1995;317:343-347.
53. Richardson TH, Jung F, Griffin KJ, et al. A 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.
54. He YQ, Harlow GR, Szklarz GD, Halpert JR. Structural determinants of progesterone hydroxylation by cytochrome P450 2B5: The role of nonsubstrate recognition site residues. Arch Biochem Biophys 1998;350:333-339.
55. 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.
56. Hasemann CA, Kurumbail RG, Boddupalli SS, Peterson JA, Deisenhofer J. Structure and function of cytochromes P450: A comparative analysis of three crystal structures. Structure 1995;3: 41-62.
57. Chang YT, Loew GH, Rettie AE, Baillie TA, Sheffels PR, Ortiz de Montellano PR. Binding of flexible ligands to proteins: valproic acid and its interaction with cytochrome P450cam. Int J Quantum Chem QBS 1993;20:161-180.
58. Harris D, Loew G. Prediction of regiospecific hydroxylation of camphor analogs by cytochrome P450cam. J Am Chem Soc 117:2738-2746. 1995;
59. Insight II 97.0. Molecular Simulations Inc., San Diego, CA; 1997.
60. Prosa II 3.0. Center of Applied Molecular Engineering, Salzburg, Austria; 1994.
61. Holm L, Sander C. Database algorithm for generating protein backbone and side-chain coordinates from a Cα trace: application to model building and detection of coordinate errors. J Mol Biol 1991;218:183-194.
62. Dunbrack RL Jr, Karplus M. Conformational analysis of the backbone-dependent rotamer preferences of protein sidechains. Nat Struct Biol 1994;1:334-340.
63. Bower MJ, Cohen FE, Dunbrack RL, Jr. Prediction of protein side-chain rotamers from a backbone-dependent rotamer library: a new homology modeling tool. J Mol Biol 1997;267:1268-1282.
64. Zhao D, Gilfoyle DJ, Smith AT, Loew GH. Refinement of 3D models of horseradish peroxidase isoenzyme C: predictions of 2D NMR assignments and substrate binding sites. Proteins 1996;26: 204-216.
65. Pearlman DA, Case DA, Caldwell JW, et al. AMBER 4.1. 1995.
66. Laskowski RA, MacArthur MW, Moss DS, Thornton JM. Pro-check: a program to check the stereochemical quality of protein structures. J Appl Cryst 26:283-291. 1993;
67. Cambridge Structural Database, Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge. CB2 1EZ, UK.
68. UNITY. TRIPOS Inc.; 1997.
69. Frisch MJ, Trucks GW, Schlegel HB, Gaussian 94 (Revision A.1), Pittsburgh: Gaussian, Inc.; 1995.
70. Breneman CM, Wiberg KB. Determining atom-centered monopoles from molecular electrostatic potentials: the need for high sampling density in formamide conformational analysis. J Comp Chem 1990;11:361-373.
71. Veronese ME, Mackenzie PI, Doecke CJ, McManus ME, Miners JO, Birkett DJ. Tolbutamide and phenytoin hydroxylations by cDNA-expressed human liver cytochrome P4502C9. Biochem Biophys Res Commun 1991;175:1112-1118.
72. Schmider J, Greenblatt DJ, von Moltke LL, Harmatz JS, Duan SX, Karsov D, Shader RI. Characterization of six in vitro reactions mediated by human cytochrome P450: application to the testing of cytochrome P450-directed antibodies. Pharmacology 1996;52:125-134.
73. Munns AJ, De Voss JJ, Hooper WD, Dickinson RG, Gillam EM. Bioactivation of phenytoin by human cytochrome P450: characterization of the mechanism and targets of covalent adduct formation. Chem Res Toxicol 1997;10:1049-1058.
74. Lewis DF. The CYP2 family: models, mutants and interactions. Xenobiotica 1998;28:617-661.
75. Klose TS, Ibeanu GC, Ghanayem BI, et al. Identification of residues 286 and 289 as critical for conferring substrate specificity of human CYP2C9 for diclofenac and ibuprofen. Arch Biochem Biophys 1998;357:240-248.
76. Goldstein JA, Faletto MB, Romkes-Sparks M, et al. Evidence that CYP2C19 is the major (S)-mephenytoin 4'-hydroxylase in humans. Biochemistry 1994;33:1743-1752.
77. Yamazaki H, Inoue K, Shimada T. Roles of two allelic variants (Arg144Cys and Ile359Leu) of cytochrome P4502C9 in the oxidation of tolbutamide and warfarin by human liver microsomes. Xenobiotica 1998;28:103-115.
78. Crespi CL, Miller VP. The R144C change in the CYP2C9*2 allele alters interaction of the cytochrome P450 with NADPH:cytochrome P450 oxidoreductase. Pharmacogenetics 1997;7:203-210.
79. Miners JO, Birkett DJ. Cytochrome P4502C9: an enzyme of major importance in human drug metabolism. Br J Clin Pharmacol 1998;45:525-538.
80. Ibeanu GC, Ghanayem BI, Linko P, Li L, Pederson LG, Goldstein JA. Identification of residues 99, 220, and 221 of human cytochrome P450 2C19 as key determinants of omeprazole activity. J Biol Chem 1996;271:12496-12501.