Evaluation of isoprenoid conformation in solution and in the active site of protein-farnesyl transferase using carbon-13 labeling in conjunction with solution- and solid-state NMR

Journal of the American Chemical Society

Volumn 122, Issue 30, 2000, Pages 7153-

  Zahn, Todd J ^a   Eilers, Markus ^c   Guo, Zhengmao ^a   Ksebati, Mohamad B ^a   Simon, Matthew ^b   Scholten, Jeffrey D ^b   Smith, Steven O ^c   Gibbs, Richard A ^a  

^a WAYNE STATE UNIVERSITY   (United States)

^b PFIZER INC   (United States)

^c STONY BROOK UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CARBON 13; FARNESOL; FARNESYL TRANS TRANSFERASE; GERANYLGERANIOL; ISOPRENOID; ORGANIC SOLVENT; WATER;

AQUEOUS SOLUTION; ARTICLE; CHEMICAL ANALYSIS; CHEMICAL LABELING; CHEMICAL STRUCTURE; COMPLEX FORMATION; CONFORMATIONAL TRANSITION; ENZYME ACTIVE SITE; MOLECULAR DYNAMICS; NUCLEAR MAGNETIC RESONANCE; SOLID STATE;

EID: 0343517159     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja000860f     Document Type: Article

References (89)

1. Gibbs, R. A. In Comprehensive Biological Catalysis; Sinnott, M. L., Ed.; Academic Press: London, 1998; Vol. 1, pp 31-118.
2. van Tamelen, E. E. Acc. Chem. Res. 1968, 1, 111-120.
3. (a) Ruzicka, L. Experientia 1953, 9, 357-396.
4. (b) Arigoni, D. Pure Appl. Chem. 1975, 41, 219-245.
5. Cane, D. E. Chem. Rev. 1990, 90, 1089-1103.
6. Abe, I.; Rohmer, M.; Prestwich, G. D. Chem. Rev. 1993, 93, 2189-2206.
7. The initial prominent medical interest in the mevalonate pathway was derived chiefly from its primary product in mammalian cells, cholesterol, and the central role that cholesterol metabolism plays in cardiovascular disease: Goldstein, J. L.; Brown, M. S. Nature 1990, 343, 425-430.
8. Cox, A. D.; Der, C. J. Biochim. Biophys. Acta 1997, 1333, F51-F71.
9. Leonard, D. M. J. Med. Chem. 1997, 40, 2971-2990.
10. Certain FTase inhibitors have exhibited great promise in animal models for many neoplasias and are currently being evaluated in clinical trials: Oliff, A. Biochim. Biophys. Acta 1999, 1423, C19-C30.
11. Casey, P. J.: Seabra, M. C. J. Biol. Chem. 1996, 271, 5289-5292.
12. Zhang, F. L.; Casey, P. J. Annu. Rev. Biochem. 1996, 65, 241-269.
13. Gibbs, R. A.; Krishnan, U.; Dolence, J. M.; Poulter, C. D. J. Org. Chem. 1995, 60, 7821-7829.
14. Mu, Y. Q.; Gibbs, R. A.; Eubanks, L.; Poulter, C. D. J. Org. Chem. 1996, 61, 8010-8015.
15. Gibbs, B. S.; Zahn, T. J.; Mu, Y. Q.; Sebolt-Leopold, J.; Gibbs, R. A. J. Med. Chem. 1999, 42, 3800-3808.
16. 16
17. (a) McNamara, D. J.; Debrusin, E.; Leonard, D. M.; Shuler, K. R.; Kaltenbronn, J. S.; Quin, J., III; Bur, S.; Thomas, C. E.; Doherty, A. M.; Scholten, J. D.; Zimmerman, K. K.; Gibbs, B. S.; Gowan, R. C.; Latash, M. P.; Leopold, W. R.; Przybranowski, S. A.; Sebolt-Leopold, J. S. J. Med. Chem. 1997, 40, 3319-3322.
18. (b) Aoyama, T.; Satoh, T.; Yonemoto, M.; Shibata, J.; Nonoshita, K.; Arai, S.; Kawakami, K.; Iwasawa, Y.; Sano, H.; Tanaka, K.; Monden, Y.; Koder, T.; Arakawa, H.; Suzuki-Takahashi, I.; Kamei, T.; Tomimoto, K. J. Med. Chem. 1998, 41, 143-147.
19. The syntheses of 2-5 have been previously reported in a preliminary communication: Zahn, T. J.; Ksebati, M.; Gibbs, R. A. Tetrahedron Lett. 1998, 39, 3991-3994.
20. Broeker, J. L.; Hoffmann, R. W.; Houk, K. N. J. Am. Chem. Soc. 1991, 113, 5006-5017.
21. Gung, B. W.; Zhu, Z.; Fouch, R. A. J. Am. Chem. Soc. 1995, 117, 1783-1788.
22. Murgolo, N. J.; Patel, A.; Stivala, S. S.; Wong, T. K. Biochemistry 1989, 28, 253-260.
23. Facke, T.; Berger, S. J. Am. Chem. Soc. 1995, 117, 9547-9550.
24. Marshall, J. L. Carbon-Carbon and Carbon-Proton NMR Couplings: Applications to Organic Stereochemistry and Conformational Analysis; Verlag Chemie International: Deerfield Beach, FL, 1983.
25. Krivdin, L. B.; Della, E. W. Prog. Nucl. Magn. Reson. Spectrosc. 1991, 23, 301-610.
26. Menger, F. M.; Carnahan, D. W. J. Am. Chem. Soc. 1986, 108, 1297-1298.
27. Menger, F. M. Angew. Chem., Int. Ed. Engl. 1991, 30, 1086-1099.
28. Breslow, R.; Maresca, L. M. Tetrahedron Lett. 1978, 887-890.
29. Di Bernardo, S.; Fato, R.; Casadio, R., Fariselli, P.; Lenaz, G. FEBS Lett. 1998, 426, 77-80.
30. Melkonian, K. A.; Ostermeyer, A. G.; Chen, J. Z.; Roth, M. G.; Brown, D. A. J. Biol. Chem. 1999, 274, 3910-3917.
31. Moffett, S.; Brown, D. A.; Linder, M. E. J. Biol. Chem. 2000, 275, 2191-2198.
32. Keep, N. H.; Barnes, M.; Barsukov, I.; Badii, R.; Lian, L. Y.; Segal, A. W.; Moody, P. C. E.; Roberts, G. C. K. Structure 1997, 5, 623-633.
33. Gosser, Y. Q.; Nomanbhoy, T. K.; Aghazadeh, B.; Manor, D.; Combs, C.; Cerione, R. A.; Rosen, M. K. Nature 1997, 387, 814-819.
34. Loew, A.; Ho, Y.-K.; Blundell, T.; Bax, B. Structure 1998, 6, 1007-1019.
35. Blokzijl, W.; Engberts, J. B. F. N. Angew. Chem., Int. Ed. Engl. 1993, 32, 1545-1579.
36. Smith, S. O.; Aschheim, K.; Groesbeek, M. Q. Rev. Biophys. 1996, 29, 395-449.
37. Levitt, M. H.; Raleigh, D. P.; Creuzet, F.; Griffin, R. G. J. Chem. Phys. 1990, 92, 6347-6364.
38. Peersen, O. B.; Groesbeek, M.; Aimoto, S.; Smith, S. O. J. Am. Chem. Soc. 1995, 117, 7228-7237.
39. McDermott, A. E.; Creuzet, F.; Gebhard, R.; van der Hoef, K.; Levitt, M. H.; Herzfeld, J.; Lugtenberg, J.; Griffin, R. G. Biochemistry 1994, 33, 6129-6136.
40. Verdegem, P. J. E.; Helmle, M.; Lugtenburg, J.; de Groot, H. J. M. J. Am. Chem. Soc. 1997, 119, 169-174.
41. For a very recent example of the application of solid-state NMR techniques to the determination of the conformation of the isoprenoid paclitaxel bound to the protein tubulin, see: Li, Y.; Poliks, B.; Cegelski, L.; Poliks, M.; Gryczynski, Z.; Piszczek, G.; Jagtap, P. G.; Studelska, D. R.; Kingston, D. G. I.; Schaefer, J.; Bane, S. Biochemistry 2000, 39, 281-291.
42. (a) Gibbs, R. A.; Krishnan, U. Tetrahedron Lett. 1994, 35, 2509-2512.
43. (b) Shao, Y.; Eummer, J. T.; Gibbs, R. A. Org. Lett. 1999, 1, 627-630.
44. Mu, Y. Q.; Gibbs, R. A. Tetrahedron Lett. 1995, 36, 5669-5672.
45. 4
46. Christensen, D. J.; Poulter, C. D. Bioorg. Med. Chem. 1994, 2, 631-638.
47. (a) Eis, K.; Schmalz, H.-G. Synthesis 1997, 202-206.
48. (b) Huang, Q.; Huang, K.; Scott, A. I. Tetrahedron Lett. 1998, 39, 2033-2036.
49. Biller, S. A.; Abt. J. W.; Pudzianowski, A. T.; Rich, L. C.; Slusarchyk, D. A.; Ciosek, C. P., Jr. Bioorg. Med. Chem. Lett. 1993, 3, 595-600.
50. Urano, S.; Otani, I.; Matsuo, M. Heterocycles 1985, 23, 2793-2796.
51. Sum, F. W.; Weiler, L. Can. J. Chem. 1979, 57, 1431-1441.
52. Comins, D. L.; Dehghani, A. Tetrahedron Lett. 1992, 33, 6299-6302.
53. (a) Courtin, J. M. L.; t'Lam, G. K.; Peters, A. J. M.; Lugtenburg, J. Recl. Trav. Chim. Pays-Bas 1985, 104, 281-288.
54. (b) Groesbeek, M.; Lugtenburg, J. Photochem. Photobiol. 1992, 56, 903-908.
55. Davisson, V. J.; Woodside, A. B.; Neal, T. R.; Stremler, K. E.; Muehlbacher, M.; Poulter, C. D. J. Org. Chem. 1986, 51, 4768-4779.
56. 13C NMR spectrum of 5 in mFTase buffer or as its sodium salt were unsucessful.
57. (b) It has recently been reported that the cmc for FPP is 12 mM, and the cmc for GGPP is 0.45 mM: Bragg, B., Ph.D. Dissertation, University of Utah, 1999.
58. Long, S. B.; Casey, P. J.; Beese, L. S. Biochemistry 1998, 37, 9612-9618.
59. (a) Yokoyama, K.; Zimmerman, K.; Scholten, J.; Gelb, M. H. J. Biol. Chem. 1997, 272, 3944-3952.
60. (b) Scholten, J. D.; Zimmerman, K. K.; Oxender, M. G.; Leonard, D. M.; Sebolt-Leopold, J.; Gowan, R.; Hupe, D. J.; J. Biol. Chem. 1997, 272, 18077-18081.
61. (a) Menger, F. M.; Dulany, M. A.; Carnahan, D. W.; Lee, L. H. J. Am. Chem. Soc. 1987, 109, 6899-6900.
62. (b) Menger, F. M.; D'Angelo, L. L. J. Am. Chem. Soc. 1988, 110, 8241-8242.
63. Note that the overall trans (extended) conformational preference seen in this study stands in sharp contrast to the significant proportion of gauche conformers calculated based on early structural studies on amorphous trans-1,4-polyisoprene: Mark, J. E. J. Am. Chem. Soc. 1966, 88, 4354-4359. Mark, J. E. J. Am. Chem. Soc. 1967, 89, 6829-6835. Flory, P. J. Statistical Mechanics of Chain Molecules; John Wiley & Sons: New York, 1969; p 192-198. However, the structures of crystalline trans-1,4- polyisoprene (Takahashi, Y.; Sato, T.; Tadokoro, H.; Tanaka, Y. J. Polym. Sci. 1973, 11, 233-248) and its inclusion complex with perhydrotriphenylene (Tonelli, A. E. Macromolecules 1990, 23, 3134-3137) indicate that in these environments this polymer does adopt an entirely trans, extended conformation. The relationship of these polymer studies to our solution studies is unclear, but we thank a reviewer for bringing them to our attention.
64. Note that the overall trans (extended) conformational preference seen in this study stands in sharp contrast to the significant proportion of gauche conformers calculated based on early structural studies on amorphous trans-1,4-polyisoprene: Mark, J. E. J. Am. Chem. Soc. 1966, 88, 4354- 4359. Mark, J. E. J. Am. Chem. Soc. 1967, 89, 6829-6835. Flory, P. J. Statistical Mechanics of Chain Molecules; John Wiley & Sons: New York, 1969; p 192-198. However, the structures of crystalline trans-1,4- polyisoprene (Takahashi, Y.; Sato, T.; Tadokoro, H.; Tanaka, Y. J. Polym. Sci. 1973, 11, 233-248) and its inclusion complex with perhydrotriphenylene (Tonelli, A. E. Macromolecules 1990, 23, 3134-3137) indicate that in these environments this polymer does adopt an entirely trans, extended conformation. The relationship of these polymer studies to our solution studies is unclear, but we thank a reviewer for bringing them to our attention.
65. Note that the overall trans (extended) conformational preference seen in this study stands in sharp contrast to the significant proportion of gauche conformers calculated based on early structural studies on amorphous trans-1,4-polyisoprene: Mark, J. E. J. Am. Chem. Soc. 1966, 88, 4354- 4359. Mark, J. E. J. Am. Chem. Soc. 1967, 89, 6829-6835. Flory, P. J. Statistical Mechanics of Chain Molecules; John Wiley & Sons: New York, 1969; p 192-198. However, the structures of crystalline trans-1,4- polyisoprene (Takahashi, Y.; Sato, T.; Tadokoro, H.; Tanaka, Y. J. Polym. Sci. 1973, 11, 233-248) and its inclusion complex with perhydrotriphenylene (Tonelli, A. E. Macromolecules 1990, 23, 3134-3137) indicate that in these environments this polymer does adopt an entirely trans, extended conformation. The relationship of these polymer studies to our solution studies is unclear, but we thank a reviewer for bringing them to our attention.
66. Note that the overall trans (extended) conformational preference seen in this study stands in sharp contrast to the significant proportion of gauche conformers calculated based on early structural studies on amorphous trans-1,4-polyisoprene: Mark, J. E. J. Am. Chem. Soc. 1966, 88, 4354- 4359. Mark, J. E. J. Am. Chem. Soc. 1967, 89, 6829-6835. Flory, P. J. Statistical Mechanics of Chain Molecules; John Wiley & Sons: New York, 1969; p 192-198. However, the structures of crystalline trans-1,4-polyisoprene (Takahashi, Y.; Sato, T.; Tadokoro, H.; Tanaka, Y. J. Polym. Sci. 1973, 11, 233-248) and its inclusion complex with perhydrotriphenylene (Tonelli, A. E. Macromolecules 1990, 23, 3134-3137) indicate that in these environments this polymer does adopt an entirely trans, extended conformation. The relationship of these polymer studies to our solution studies is unclear, but we thank a reviewer for bringing them to our attention.
67. Note that the overall trans (extended) conformational preference seen in this study stands in sharp contrast to the significant proportion of gauche conformers calculated based on early structural studies on amorphous trans-1,4-polyisoprene: Mark, J. E. J. Am. Chem. Soc. 1966, 88, 4354- 4359. Mark, J. E. J. Am. Chem. Soc. 1967, 89, 6829-6835. Flory, P. J. Statistical Mechanics of Chain Molecules; John Wiley & Sons: New York, 1969; p 192-198. However, the structures of crystalline trans-1,4- polyisoprene (Takahashi, Y.; Sato, T.; Tadokoro, H.; Tanaka, Y. J. Polym. Sci. 1973, 11, 233-248) and its inclusion complex with perhydrotriphenylene (Tonelli, A. E. Macromolecules 1990, 23, 3134-3137) indicate that in these environments this polymer does adopt an entirely trans, extended conformation. The relationship of these polymer studies to our solution studies is unclear, but we thank a reviewer for bringing them to our attention.
68. Breslow, R. Acc. Chem. Res. 1991, 24, 159-164.
69. Engberts, J. B. F. N. Pure Appl. Chem. 1995, 67, 823-828.
70. Gajewski, J. J. Acc. Chem. Res 1997, 30, 219-225.
71. Jiang, X.-K. Acc. Chem. Res. 1988, 21, 362-367.
72. Jiang, X.-K.; Ji, G.-Z.; Tu, B.; Zhang, X.-Y.; Shi, J.-L.; Chen, X. J. Am. Chem. Soc. 1995, 117, 12679-12682.
73. (a) Vander Velde, D. G.; Georg, G. I.; Grunewald, G. L.; Gunn, C. W.; Mitscher, L. A. J. Am. Chem. Soc. 1993, 115, 11650-11651 and references therein.
74. (b) Snyder, J. P.; Nevins, N.; Cicero, D. O.; Jansen, J. J. Am. Chem. Soc. 2000. 122, 724-725 and references therein.
75. Wiley, R. A.; Rich, D. H. Med. Res. Rev. 1993, 3, 327-384.
76. Newcomb, L. F.; Haque, T. S.; Gellman, S. H. J. Am. Chem. Soc. 1995, 117, 6509-6519.
77. Gardner, R. R.; Christianson, L. A.; Gellman, S. H. J. Am. Chem. Soc. 1997, 119, 5041-5042.
78. Stradley, S. J.; Rizo, J.; Gierasch, L. M. Biochemistry 1993, 32, 12586-12590.
79. Koblan, K. S.; Culberson, J. C.; deSolms, S. J.; Giuliani, E. A.; Mosser, S. D.; Omer, C. A.; Pitzenberger, S. M.; Bogusky, M. J. Protein Sci. 1995, 4, 681-688.
80. Park, H. W.; Boduluri, S. R.; Moomaw, J. F.; Casey, P. J.; Beese, L. S. Science 1997, 275, 1800-1804.
81. Dunten, P.; Kammlott, U.; Crowther, R.; Weber, D.; Palermo, R.; Birktoft, J. Biochemistry 1998, 37, 7907-7912.
82. Strickland, C. L.; Windsor, W. T.; Syto, R.; Wang, L.; Bond, R.; Wu, Z.; Schwanz, J.; Le, H. V.; Beese, L. S.; Weber, P. C. Biochemistry 1998, 37, 16601-16611.
83. Long, S. B.; Casey, P. J.; Beese, L. S. Struct. Folding Des. 2000, 8, 209-222.
84. Cane, D. E. Acc. Chem. Res. 1985, 18, 220-226.
85. Lesburg, C. A.; Zhai, G.; Cane, D. E.; Christianson, D. W. Science 1997, 277, 1820-1824.
86. Cassidy, P. B.; Dolence, J. M.; Poulter, C. D. Methods Enzymol. 1995, 250, 30-43.
87. Alder, B. J.; Wainwright, T. E. J. Chem. Phys. 1957, 27, 1208-1218.
88. Metz, G.; Wu, X.; Smith, S. O. J. Magn. Reson. A 1994. 110, 219-227.
89. Bennett, A. E.; Rientstra, C. M.; Auger, M.; Lakshimi, K. V.; Griffin, R. G. J. Chem. Phys. 1995. 103, 6951-6958.