Crystal structure of inhibitor-bound P450BM-3 reveals open conformation of substrate access channel

Biochemistry

Volumn 47, Issue 12, 2008, Pages 3662-3670

  Haines, Donovan C ^b   Chen, Baozhi ^a   Tomchick, Diana R ^a   Bondlela, Muralidhar ^a   Hegde, Amita ^a   Machius, Mischa ^a   Peterson, Julian A ^a  

^a UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER   (United States)

^b UNIVERSITY OF TEXAS AT DALLAS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HEME DOMAIN; SUBSTRATE ACCESS CHANNEL;

AMINO ACIDS; CONFORMATIONS; CRYSTAL STRUCTURE; FATTY ACIDS; NITROGEN; PROTEINS;

ENZYME INHIBITION;

AMINO ACID; CYTOCHROME P450 BM3; ENZYME INHIBITOR; FATTY ACID; IMIDAZOLE DERIVATIVE; LAURIC ACID; N (12 IMIDAZOLYLDODECANOYL)LEUCINE; NITROGEN; UNCLASSIFIED DRUG;

ARTICLE; COMPLEX FORMATION; CONFORMATIONAL TRANSITION; CRYSTAL STRUCTURE; ENZYME BINDING; ENZYME SUBSTRATE; MOLECULAR INTERACTION; PRIORITY JOURNAL;

BACTERIAL PROTEINS; CRYSTALLIZATION; CRYSTALLOGRAPHY, X-RAY; CYTOCHROME P-450 ENZYME SYSTEM; ENZYME INHIBITORS; FATTY ACIDS; HEME; IMIDAZOLES; LEUCINE; MIXED FUNCTION OXYGENASES; MODELS, MOLECULAR; NADP; OXIDATION-REDUCTION; PROTEIN CONFORMATION;

EID: 41149151753     PISSN: 00062960     EISSN: None     Source Type: Journal    
DOI: 10.1021/bi7023964     Document Type: Article

References (54)

1. Palmer, C. N., Axen, E., Hughes, V., and Wolf, C. R. (1998) The repressor protein, Bm3R1, mediates an adaptive response to toxic fatty acids in Bacillus megaterium. J. Biol. Chem. 273, 18109-18116.
2. Narhi, L. O., Kim, B. H., Stevenson, P. M., and Fulco, A. J. (1983) Partial characterization of a barbiturate-induced cytochrome P-450-dependent fatty acid monooxygenase from Bacillus megaterium. Biochem. Biophys. Res. Commun. 116, 851-858.
3. Wen, L. P., and Fulco, A. J. (1987) Cloning of the gene encoding a catalytically self-sufficient cytochrome P-450 fatty acid monooxygenase induced by barbiturates in Bacillus megaterium and its functional expression and regulation in heterologous (Escherichia coli) and homologous (Bacillus megaterium) hosts. J. Biol. Chem. 262, 6676-6682.
4. Narhi, L. O., and Fulco, A. J. (1986) Characterization of a catalytically self-sufficient 119,000-dalton cytochrome P-450 monooxygenase induced by barbiturates in Bacillus megaterium. J. Biol. Chem. 261, 7160-7169.
5. Narhi, L. O., and Fulco, A. J. (1987) Identification and characterization of two functional domains in cytochrome P-450BM-3, a catalytically self-sufficient monooxygenase induced by barbiturates in Bacillus megaterium. J. Biol. Chem. 262, 6683-6690.
6. Miura, Y., and Fulco, A. J. (1975) Omega-1, Omega-2 and Omega-3 hydroxylation of long-chain fatty acids, amides and alcohols by a soluble enzyme system from Bacillus megaterium. Biochim. Biophys. Acta 388, 305-317.
7. Capdevila, J. H., Wei, S., Helvig, C., Falck, J. R., Belosludtsev, Y., Truan, G., Graham-Lorence, S. E., and Peterson, J. A. (1996) The highly stereoselective oxidation of polyunsaturated fatty acids by cytochrome P450BM-3. J. Biol. Chem. 271, 22663-22671.
8. Sevrioukova, I. F., Li, H., Zhang, H., Peterson, J. A., and Poulos, T. L. (1999) Structure of a cytochrome P450-redox partner electron-transfer complex. Proc. Natl. Acad. Sci. U.S.A. 96, 1863-1868.
9. Li, H., and Poulos, T. L. (1997) The structure of the cytochrome p450BM-3 haem domain complexed with the fatty acid substrate, palmitoleic acid. Nat. Struct. Biol. 4, 140-146.
10. Yeom, H., Sligar, S. G., Li, H., Poulos, T. L., and Fulco, A. J. (1995) The role of Thr268 in oxygen activation of cytochrome P450BM-3. Biochemistry 34, 14733-14740.
11. Haines, D. C., Tomchick, D. R., Machius, M., and Peterson, J. A. (2001) Pivotal role of water in the mechanism of P450BM-3. Biochemistry 40, 13456-13465.
12. Ravichandran, K. G., Boddupalli, S. S., Hasemann, C. A., Peterson, J. A., and Deisenhofer, J. (1993) Crystal structure of hemoprotein domain of P450BM-3, a prototype for microsomal P450's. Science 261, 731-736.
13. Yun, C. H., Kim, K. H., Kim, D. H., Jung, H. C., and Pan, J. G. (2007) The bacterial P450 BM3: a prototype for a biocatalyst with human P450 activities. Trends Biotechnol. 25, 289-298.
14. Pflug, S., Richter, S. M., and Urlacher, V. B. (2007) Development of a fed-batch process for the production of the cytochrome P450 monooxygenase CYP102A1 from Bacillus megaterium in E. coli. J. Biotechnol. 129, 481-488.
15. Appel, D., Lutz-Wahl, S., Fischer, P., Schwaneberg, U., and Schmid, R. D. (2001) A P450 BM-3 mutant hydroxylates alkanes, cycloalkanes, arenes and heteroarenes. J. Biotechnol. 88, 167-171.
16. Otey, C. R., Landwehr, M., Endelman, J. B., Hiraga, K., Bloom, J. D., and Arnold, F. H. (2006) Structure-guided recombination creates an artificial family of cytochromes P450. PLoS Biol. 4, e112.
17. Meinhold, P., Peters, M. W., Chen, M. M., Takahashi, K., and Arnold, F. H. (2005) Direct conversion of ethane to ethanol by engineered cytochrome P450 BM3. ChemBioChem 6, 1765-1768.
18. Munzer, D. F., Meinhold, P., Peters, M. W., Feichtenhofer, S., Griengl, H., Arnold, F. H., Glieder, A., and de Raadt, A. (2005) Stereoselective hydroxylation of an achiral cyclopentanecarboxylic acid derivative using engineered P450s BM-3. Chem. Commun. (Cambridge), 2597-2599.
19. Seng, W. T., Arnold, F. H., and Schwaneberg, U. (2004) Laboratory evolution of cytochrome p450 BM-3 monooxygenase for organic cosolvents. Biotechnol. Bioeng. 85, 351-358.
20. Peters, M. W., Meinhold, P., Glieder, A., and Arnold, F. H. (2003) Regio- and enantioselective alkane hydroxylation with engineered cytochromes P450 BM-3. J. Am. Chem. Soc. 125, 13442-13450.
21. Fairhead, M., Giannini, S., Gillam, E. M., and Gilardi, G. (2005) Functional characterisation of an engineered multidomain human P450 2E1 by molecular Lego. J. Biol. Inorg. Chem. 10, 842-853.
22. Sieber, V., Martinez, C. A., and Arnold, F. H. (2001) Libraries of hybrid proteins from distantly related sequences. Nat. Biotechnol. 19, 456-460.
23. Dodhia, V. R., Fantuzzi, A., and Gilardi, G. (2006) Engineering human cytochrome P450 enzymes into catalytically self-sufficient chimeras using molecular Lego. J. Biol. Inorg. Chem. 11, 903-916.
24. Remmer, H., Schenkman, J., Estabrook, R. W., Sasame, H., Gillette, J., Narasimhulu, S., Cooper, D. Y., and Rosenthal, O. (1966) Drug interaction with hepatic microsomal cytochrome. Mol. Pharmacol. 2, 187-190.
25. Peterson, J. A., Ullrich, V., and Hildebrandt, A. G. (1971) Methyrapone interaction with Pseudomonas putida cytochrome P-405. Arch. Biochem. Biophys. 145, 531-542.
26. Noble, M. A., Quaroni, L., Chumanov, G. D., Turner, K. L., Chapman, S. K., Hanzlik, R. P., and Munro, A. W. (1998) Imidazolyl carboxylic acids as mechanistic probes of flavocytochrome P-450 BM3. Biochemistry 37, 15799-15807.
27. Jovanovic, T., and McDermott, A. E. (2005) Observation of ligand binding to cytochrome P450 BM-3 by means of solid-state NMR spectroscopy. J. Am. Chem. Soc. 127, 13816-13821.
28. Ravindranathan, K. P., Gallicchio, E., McDermott, A. E., and Levy, R. M. (2007) Conformational dynamics of substrate in the active site of cytochrome P450 BM-3/NPG complex: insights from NMR order parameters. J. Am. Chem. Soc. 129, 474-475.
29. Hegde, A., Haines, D. C., Bondlela, M., Chen, B., Schaffer, N., Tomchick, D. R., Machius, M., Nguyen, H., Chowdhary, P. K., Stewart, L., Lopez, C., and Peterson, J. A. (2007) Interactions of substrates at the surface of p450s can greatly enhance substrate potency. Biochemistry 46, 14010-14017.
30. Sevrioukova, I., Truan, G., and Peterson, J. A. (1996) The flavoprotein domain of P450BM-3: expression, purification, and properties of the flavin adenine dinucleotide- and flavin mononucleotide-binding subdomains. Biochemistry 35, 7528-7535.
31. Boddupalli, S. S., Hasemann, C. A., Ravichandran, K. G., Lu, J. Y., Goldsmith, E. J., Deisenhofer, J., and Peterson, J. A. (1992) Crystallization and preliminary x-ray diffraction analysis of P450terp and the hemoprotein domain of P450BM-3, enzymes belonging to two distinct classes of the cytochrome P450 superfamily. Proc. Natl. Acad. Sci. U.S.A. 89, 5567-5571.
32. Omura, T., and Sato, R. (1964) The Carbon Monoxide-Binding Pigment of Liver Microsomes. I. Evidence for Its Hemoprotein Nature. J. Biol. Chem. 239, 2370-2378.
33. Lu, P., Alterman, M. A., Chaurasia, C. S., Bambal, R. B., and Hanzlik, R. P. (1997) Heme-coordinating analogs of lauric acid as inhibitors of fatty acid omega-hydroxylation. Arch. Biochem. Biophys. 337, 1-7.
34. Alterman, M. A., Chaurasia, C. S., Lu, P., Hardwick, J. P., and Hanzlik, R. P. (1995) Fatty acid discrimination and omega-hydroxylation by cytochrome P450 4A1 and a cytochrome P4504A1/NADPH-P450 reductase fusion protein. Arch. Biochem. Biophys. 320, 289-296.
35. Devadas, B., Freeman, S. K., Zupec, M. E., Lu, H. F., Nagarajan, S. R., Kishore, N. S., Lodge, J. K., Kuneman, D. W., McWherter, C. A., Vinjamoori, D. V., Getman, D. P., Gordon, J. I., and Sikorski, J. A. (1997) Design and synthesis of novel imidazole-substituted dipeptide amides as potent and selective inhibitors of Candida albicans myristoylCoA:protein N-myristoyltransferase and identification of related tripeptide inhibitors with mechanism-based antifungal activity. J. Med. Chem. 40, 2609-2625.
36. Otwinowski, Z., and Minor, W. (1997) Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276, 307-326.
37. Jones, T. A., Zou, J. Y., and Cowan, S. W. (1991) Improved methods for building protein models in electron density maps and the location of errors in these models. Acta Crystallogr., Sect. A: Found. Crystallogr. 47, 110-119.
38. Brugner, A. T., Adams, P. D., Clore, G. M., DeLano, W. L., Gros, P., Grosse-Kunstleve, R. W., Jiang, J. S., Kuszewski, J., Nilges, M., Pannu, N. S., Read, R. J., Rice, L. M., Simonson, T., and Warren, G. L. (1998) Crystallography & NMR system: A new software suite for macromolecular structure determination. Acta Crystallogr., Sect. D: Biol.Crystallogr. 54, 905-921.
39. Murshudov, G. N., Vagin, A. A., and Dodson, E. J. (1997) Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr., Sect. D: Biol. Crystallogr. 53, 240-255.
40. DeLano, W. L. (2002) The PyMOL Molecular Graphics System, DeLano Scientific Co., Palo Alto, CA.
41. Boddupalli, S. S., Estabrook, R. W., and Peterson, J. A. (1990) Fatty acid monooxygenation by cytochrome P-450BM-3. J. Biol. Chem. 265, 4233-4239.
42. Zhao, Y., White, M. A., Muralidhara, B. K., Sun, L., Halpert, J. R., and Stout, C. D. (2006) Structure of microsomal cytochrome P450 2B4 complexed with the antifungal drug bifonazole: insight into P450 conformational plasticity and membrane interaction. J. Biol. Chem. 281, 5973-5981.
43. Scott, E. E., White, M. A., He, Y. A., Johnson, E. F., Stout, C. D., and Halpert, J. R. (2004) Structure of mammalian cytochrome P450 2B4 complexed with 4-(4-chlorophenyl)imidazole at 1.9-Å resolution: insight into the range of P450 conformations and the coordination of redox partner binding. J. Biol. Chem. 279, 27294-27301.
44. Verras, A., Alian, A., and de Montellano, P. R. (2006) Cytochrome P450 active site plasticity: attenuation of imidazole binding in cytochrome P450. (cam) by an L244A mutation. Protein Eng., Des. Sel. 19, 491-496.
45. Yano, J. K., Koo, L. S., Schuller, D. J., Li, H., Ortiz de Montellano, P. R., and Poulos, T. L. (2000) Crystal structure of a thermophilic cytochrome P450 from the archaeon Sulfolobus solfataricus. J. Biol. Chem. 275, 31086-31092.
46. Poulos, T. L., and Howard, A. J. (1987) Crystal structures of metyrapone- and phenylimidazole-inhibited complexes of cytochrome P-450cam. Biochemistry 26, 8165-8174.
47. Lovell, S. C., Davis, I. W., Arendall, W. B., III, de Bakker, P. I., Word, J. M., Prisant, M. G., Richardson, J. S., and Richardson, D. C. (2003) Structure validation by Calpha geometry: phi,psi and Cbeta deviation. Proteins 50, 437-450.
48. Murataliev, M. B., and Feyereisen, R. (1996) Functional interactions in cytochrome P450BM3. Fatty acid substrate binding alters electron-transfer properties of the flavoprotein domain. Biochemistry 35, 15029-15037.
49. Modi, S., Primrose, W. U., Boyle, J. M., Gibson, C. F., Lian, L. Y., and Roberts, G. C. K. (1995) NMR studies of substrate binding to cytochrome P450 BM3: comparisons to cytochrome P450 cam. Biochemistry 34, 8982-8988.
50. Modi, S., Sutcliffe, M. J., Primrose, W. U., Lian, L. Y., and Roberts, G. C. K. (1996) The catalytic mechanism of cytochrome P450 BM3 involves a 6 Å movement of the bound substrate on reduction. Nat. Struct. Biol. 3, 414-417.
51. Haines, D. C. (2006) A role for the strained phenylalanine ring rotation induced by substrate binding to cytochrome CYP102A1. Protein Pept. Lett. 13, 977-980.
52. Rock, D. A., Perkins, B. N., Wahlstrom, J., and Jones, J. P. (2003) A method for determining two substrates binding in the same active site of cytochrome P450BM3: an explanation of high energy omega product formation. Arch. Biochem. Biophys. 416, 9-16.
53. Parang, K., and Cole, P. A. (2002) Designing bisubstrate analog inhibitors for protein kinases. Pharmacol. Ther. 93, 145-157.
54. Page, M. I., and Jencks, W. P. (1971) Entropic contributions to rate accelerations in enzymic and intramolecular reactions and the chelate effect. Proc. Natl. Acad. Sci. U.S.A. 68, 1678-1683.