Reaction path of protein farnesyltransferase at atomic resolution

Nature

Volumn 419, Issue 6907, 2002, Pages 645-650

  Long, Stephen B ^a   Casey, Patrick J ^a   Beese, Lorena S ^a  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CATALYSIS; LIPIDS; TUMORS;

CLINICAL TRIALS;

ENZYMES;

PHENYL GROUP; PROTEIN FARNESYLTRANSFERASE; PROTEIN FARNESYLTRANSFERASE INHIBITOR; RAB PROTEIN;

PROTEIN;

ARTICLE; ENZYME BINDING; ENZYME MECHANISM; ENZYME SPECIFICITY; NONHUMAN; PRIORITY JOURNAL; PROTEIN STRUCTURE;

ALKYL AND ARYL TRANSFERASES; ANIMALS; CATALYSIS; CELL LINE; CRYSTALLOGRAPHY, X-RAY; MODELS, MOLECULAR; PROTEIN CONFORMATION; PROTEIN ISOPRENYLATION; RATS; RECOMBINANT PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY;

EID: 0037057707     PISSN: 00280836     EISSN: None     Source Type: Journal    
DOI: 10.1038/nature00986     Document Type: Article

References (30)

1. Casey, P. J. & Seabra, M. C. Protein prenyltransferases. J. Biol. Chem. 271, 5289-5292 (1996).
2. Adjei, A. A. Blocking oncogenic Ras signalling for cancer therapy. J. Natl Cancer Inst. 93, 1062-1074 (2001).
3. Johnston, S. R. D. Farnesyl transferase inhibitors: a novel targeted therapy for cancer. Lancet Oncol. 2, 18-26 (2001).
4. Karp, J. E. et al. Current status of clinical trials of farnesyltransferase inhibitors. Curr. Opin. Oncol. 13, 470-476 (2001).
5. Huang, C., Hightower, K. E. & Fierke, C. A. Mechanistic studies of rat protein farnesyltransferase indicate an associative transition state. Biochemistry 39, 2593-2602 (2000).
6. Park, H.-W., Boduluri, S. R., Moomaw, J. F., Casey, P. J. & Beese, L. S. Crystal structure of protein farnesyltransferase at 2.25 Å resolution. Science 275, 1800-1804 (1997).
7. Long, S., Casey, P. J. & Beese, L. S. Co-crystal structure of protein farnesyltransferase with a farnesyl diphosphate substrate. Biochemistry 37, 9612-9618 (1998).
8. Strickland, C. L. et al. Crystal structure of farnesyl transferase complexed with a CaaX peptide and farnesyl diphosphate analogue. Biochemistry 37, 16601-16611 (1998).
9. Long, S. B., Casey, P. J. & Beese, L. S. The basis for K-Ras4B binding specificity to protein farnesyltransferase revealed by 2 Å resolution ternary complex structures. Struct. Fold. Des. 8, 209-222 (2000).
10. Furfine, E. S., Leban, J. J., Landavazo, A., Moomaw, J. F. & Casey, P. J. Protein farnesyltransferase: Kinetics of farnesyl pytophosphate binding and product release. Biochemistry 34, 6857-6862 (1995).
11. Dolence, J. M., Rozema, D. B. & Poulter, C. D. Yeast protein farnesyltransferase. Site-directed mutagenesis of conserved residues in the beta-subunit. Biochemistry 36, 9246-9252 (1997).
12. Kral, A. M. et al. Mutational analysis of conserved residues of the beta-subunit of human farnesylprotein transferase. J. Biol. Chem. 272, 27319-27323 (1997).
13. Wu, Z. et al. Farnesyl protein transferase: identification of K164α and Y300β as catalytic residues by mutagenesis and kinetic studies. Biochemistry 38, 11239-11249 (1999).
14. Reiss, Y., Brown, M. S. & Goldstein, J. L. Divalent cation and prenyl pyrophosphate specificities of the protein farnesyltransferase from rat brain, a zinc metalloenzyme. J. Biol. Chem. 267, 6403-6408 (1992).
15. Mathis, J. R. & Poulter, C. D. Yeast protein farnesyltransferase: a pre-steady-state kinetic analysis. Biochemistry 36, 6367-6376 (1997).
16. Yokoyama, K., Zimmerman, K., Scholten, J. & Gelb, M. H. Differential prenyl pyrophosphate binding to mammalian protein geranylgeranyltransferase-I and protein farnesyltransferase and its consequence on the specificity of protein prenylation. J. Biol. Chem. 272, 3944-3952 (1997).
17. Tschantz, W. R., Furfine, E. S. & Casey, P. J. Substrate binding is required for release of product from mammalian protein farnesyltransferase. J. Biol. Chem. 272, 9989-9993 (1997).
18. Stradley, S. J., Rizo, J. & Gierasch, L. M. Conformation of a heptapeptide substrate bound to protein farnesyltransferase. Biochemistry 32, 12586-12590 (1993).
19. Koblan, K. S. et al. NMR studies of novel inhibitors bound to farnesyl-protein transferase. Prot. Sci. 4, 681-688 (1995).
20. Cate, J. H., Yusupov, M. M., Yusupova, G. Z., Earnest, T. N. & Noller, H. F. X-ray crystal structures of 70S ribosome functional complexes. Science 285, 2095-2104 (1999).
21. Farnsworth, C. C., Seabra, M. C., Ericsson, L. H., Gelb, M. H. & Glomset, J. A. Rab geranylgeranyl transferase catalyzes the geranylgeranylation of adjacent cysteines in the small GTPases Rab1A, Rab3A, and Rab5A. Proc. Natl Acad. Sci. USA 91, 11963-11967 (1994).
22. Novick, P. & Zerial, M. The diversity of Rab proteins in vesicle transport. Curr. Opin. Cell Biol. 9, 496-504 (1997).
23. Thoma, N. H., Niculae, A., Goody, R. S. & Alexandrov, K. Double prenylation by RabGGTase can proceed without dissociation of the mono-prenylated intermediate. J. Biol. Chem. 276, 48631-48636 (2001).
24. Zhang, H., Seabra, M. C. & Deisenhofer, J. Crystal structure of Rab geranylgeranyltransferase at 2.0 Å resolution. Struct. Fold. Des. 8, 241-251 (2000).
25. Desnoyers, L. & Seabra, M. C. Single prenyl-binding site on protein prenyl transferases. Proc. Natl Acad. Sci. USA 95, 12266-12270 (1998).
26. Thoma, N. H. et al. Allosteric regulation of substrate binding and product release in geranylgeranyltransferase type II. Biochemistry 40, 268-274 (2001).
27. Ashby, M. N. CaaX converting enzymes. Curr. Opin. Lipidol. 9, 99-102 (1998).
28. Long, S. B., Hancock, P. J., Kral, A. M., Hellinga, H. W. & Beese, L. S. The crystal structure of human protein farnesyltransferase reveals the basis for inhibition by CaaX tetrapeptides and their mimetics. Proc. Natl Acad. Sci. USA 98, 12948-12953 (2001).
29. Bell, I. M. G. et al. 3-Aminopyrrolidinone farnesyltransferase inhibitors: design of macrocyclic compounds with improved pharmacokinetics and excellent cell potency. J. Med. Chem. 45, 2388-2409 (2002).
30. Strickland, C. L. et al. Tricyclic farnesyl protein transferase inhibitors: crystallographic and calorimetric studies of structure-activity relationships. J. Med. Chem. 42, 2125-2135 (1999).