Structural Basis for Binding and Selectivity of Antimalarial and Anticancer Ethylenediamine Inhibitors to Protein Farnesyltransferase

Chemistry and Biology

Volumn 16, Issue 2, 2009, Pages 181-192

  Hast, Michael A ^a   Fletcher, Steven ^b   Cummings, Christopher G ^b   Pusateri, Erin E ^b   Blaskovich, Michelle A ^c   Rivas, Kasey ^d   Gelb, Michael H ^d   Van Voorhis, Wesley C ^d   Sebti, Said M ^c   Hamilton, Andrew D ^b   Beese, Lorena S ^a  

^a DUKE UNIVERSITY MEDICAL CENTER   (United States)

^b YALE UNIVERSITY   (United States)

^c H LEE MOFFITT CANCER CENTER AND RESEARCH INSTITUTE   (United States)

^d UNIVERSITY OF WASHINGTON   (United States)

Author keywords

CHEMBIO; MICROBIO; PROTEINS

Indexed keywords

ANTIMALARIAL AGENT; ANTINEOPLASTIC AGENT; ENZYME INHIBITOR; ETHYLENEDIAMINE; ETHYLENEDIAMINE DERIVATIVE; FARNESYL TRANS TRANSFERASE; PROTOZOAL PROTEIN;

ANIMAL; ARTICLE; CHEMISTRY; DRUG ANTAGONISM; ENZYME SPECIFICITY; ENZYMOLOGY; HUMAN; METABOLISM; PLASMODIUM FALCIPARUM; PROTEIN BINDING; PROTEIN CONFORMATION; RAT; STRUCTURAL HOMOLOGY; STRUCTURE ACTIVITY RELATION; SYNTHESIS; TUMOR CELL LINE; X RAY CRYSTALLOGRAPHY;

ANIMALS; ANTIMALARIALS; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; CRYSTALLOGRAPHY, X-RAY; ENZYME INHIBITORS; ETHYLENEDIAMINES; FARNESYLTRANSTRANSFERASE; HUMANS; PLASMODIUM FALCIPARUM; PROTEIN BINDING; PROTEIN CONFORMATION; PROTOZOAN PROTEINS; RATS; STRUCTURAL HOMOLOGY, PROTEIN; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY;

MAMMALIA; PLASMODIUM FALCIPARUM; PROTOZOA;

EID: 60849087366     PISSN: 10745521     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.chembiol.2009.01.014     Document Type: Article

References (40)

1. Basso A.D., Kirschmeier P., and Bishop W.R. Lipid posttranslational modifications. Farnesyl transferase inhibitors. J. Lipid Res. 47 (2006) 15-31
2. Bell I.M., Gallicchio S.N., Abrams M., Beese L.S., Beshore D.C., Bhimnathwala H., Bogusky M.J., Buser C.A., Culberson J.C., Davide J., et al. 3-Aminopyrrolidinone farnesyltransferase inhibitors: design of macrocyclic compounds with improved pharmacokinetics and excellent cell potency. J. Med. Chem. 45 (2002) 2388-2409
3. Bennett-Lovsey R.M., Herbert A.D., Sternberg M.J., and Kelley L.A. Exploring the extremes of sequence/structure space with ensemble fold recognition in the program Phyre. Proteins 70 (2008) 611-625
4. Carrico D., Ohkanda J., Kendrick H., Yokoyama K., Blaskovich M.A., Bucher C.J., Buckner F.S., Van Voorhis W.C., Chakrabarti D., Croft S.L., et al. In vitro and in vivo antimalarial activity of peptidomimetic protein farnesyltransferase inhibitors with improved membrane permeability. Bioorg. Med. Chem. 12 (2004) 6517-6526
5. Casey P.J., and Seabra M.C. Protein prenyltransferases. J. Biol. Chem. 271 (1996) 5289-5292
6. Casey P.J., and Seabra M.C. Protein prenyltransferases. J. Biol. Chem. 271 (1996) 5289-5292
7. Chen W.J., Moomaw J.F., Overton L., Kost T.A., and Casey P.J. High level expression of mammalian protein farnesyltransferase in a baculovirus system. The purified protein contains zinc. J. Biol. Chem. 268 (1993) 9675-9680
8. 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) W615-619
9. Delano W.L. The PyMOL molecular graphics system (2002), DeLano Scientific, San Carlos, CA
10. Dolence J.M., Cassidy P.B., Mathis J.R., and Poulter C.D. Yeast protein farnesyltransferase: steady-state kinetic studies of substrate binding. Biochemistry 34 (1995) 16687-16694
11. Eastman R.T., White J., Hucke O., Bauer K., Yokoyama K., Nallan L., Chakrabarti D., Verlinde C.L., Gelb M.H., Rathod P.K., et al. Resistance to a protein farnesyltransferase inhibitor in Plasmodium falciparum. J. Biol. Chem. 280 (2005) 13554-13559
12. Eastman R.T., Buckner F.S., Yokoyama K., Gelb M.H., and Van Voorhis W.C. Thematic review series: lipid posttranslational modifications. Fighting parasitic disease by blocking protein farnesylation. J. Lipid Res. 47 (2006) 233-240
13. Eastman R.T., White J., Hucke O., Yokoyama K., Verlinde C.L., Hast M.A., Beese L.S., Gelb M.H., Rathod P.K., and Van Voorhis W.C. Resistance mutations at the lipid substrate binding site of Plasmodium falciparum protein farnesyltransferase. Mol. Biochem. Parasitol. 152 (2007) 66-71
14. Emsley P., and Cowtan K. Coot: model-building tools for molecular graphics. Acta Crystallogr. D Biol. Crystallogr. 60 (2004) 2126-2132
15. Furfine E.S., Leban J.J., Landavazo A., Moomaw J.F., and Casey P.J. Protein farnesyltransferase: Kinetics of farnesyl pyrophosphate binding and product release. Biochemistry 34 (1995) 6857-6862
16. Glenn M.P., Chang S.Y., Hucke O., Verlinde C.L., Rivas K., Horney C., Yokoyama K., Buckner F.S., Pendyala P.R., Chakrabarti D., et al. Structurally simple farnesyltransferase inhibitors arrest the growth of malaria parasites. Angew. Chem. Int. Ed. Engl. 44 (2005) 4903-4906
17. Glenn M.P., Chang S.Y., Horney C., Rivas K., Yokoyama K., Pusateri E.E., Fletcher S., Cummings C.G., Buckner F.S., Pendyala P.R., et al. Structurally simple, potent, Plasmodium selective farnesyltransferase inhibitors that arrest the growth of malaria parasites. J. Med. Chem. 49 (2006) 5710-5727
18. Guex N., and Peitsch M.C. SWISS-MODEL and the Swiss-PdbViewer: an environment for comparative protein modeling. Electrophoresis 18 (1997) 2714-2723
19. Hast M.A., and Beese L.S. Structure of protein geranylgeranyltransferase-I from the human pathogen Candida albicans complexed with a lipid substrate. J. Biol. Chem. 283 (2008) 31933-31940
20. Hightower K.E., Huang C.-C., Casey P.J., and Fierke C.A. H-ras peptide and protein substrates bind protein farnesyltransferase as an ionized thiolate. Biochemistry 37 (1998) 15555-15562
21. Huang C., Hightower K.E., and Fierke C.A. Mechanistic studies of rat protein farnesyltransferase indicate an associative transition state. Biochemistry 39 (2000) 2593-2602
22. Konstantinopoulos P.A., Karamouzis M.V., and Papavassiliou A.G. Post-translational modifications and regulation of the RAS superfamily of GTPases as anticancer targets. Nat. Rev. Drug Discov. 6 (2007) 541-555
23. Lane K.T., and Beese L.S. Thematic review series: lipid posttranslational modifications. Structural biology of protein farnesyltransferase and geranylgeranyltransferase type I. J. Lipid Res. 47 (2006) 681-699
24. Long S.B., Casey P.J., and Beese L.S. Cocrystal structure of protein farnesyltransferase complexed with a farnesyl diphosphate substrate. Biochemistry 37 (1998) 9612-9618
25. Long S.B., Casey P.J., and Beese L.S. The basis for K-Ras4B binding specificity to protein farnesyltransferase revealed by 2 A resolution ternary complex structures. Structure 8 (2000) 209-222
26. Long S.B., Hancock P.J., Kral A.M., Hellinga H.W., and 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 (2001) 12948-12953
27. Long S.B., Casey P.J., and Beese L.S. Reaction path of protein farnesyltransferase at atomic resolution. Nature 419 (2002) 645-650
28. Murshudov G.N., Vagin A.A., and Dodson E.J. Refinement of macromolecular structures by the maximum-likelihood method. Acta Crystallogr. D Biol. Crystallogr. 53 (1997) 240-255
29. Otwinowski Z., and Minor W. Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 276 (1997) 307-326
30. Pickett J.S., Bowers K.E., Hartman H.L., Fu H.W., Embry A.C., Casey P.J., and Fierke C.A. Kinetic studies of protein farnesyltransferase mutants establish active substrate conformation. Biochemistry 42 (2003) 9741-9748
31. Reid T.S., and Beese L.S. Crystal structures of the anticancer clinical candidates R115777 (Tipifarnib) and BMS-214662 complexed with protein farnesyltransferase suggest a mechanism of FTI selectivity. Biochemistry 43 (2004) 6877-6884
32. Reid T.S., Long S.B., and Beese L.S. Crystallographic analysis reveals that anticancer clinical candidate L-778,123 inhibits protein farnesyltransferase and geranylgeranyltransferase-I by different binding modes. Biochemistry 43 (2004) 9000-9008
33. Reid T.S., Terry K.L., Casey P.J., and Beese L.S. Crystallographic analysis of CaaX prenyltransferases complexed with substrates defines rules of protein substrate selectivity. J. Mol. Biol. 343 (2004) 417-433
34. Storoni L.C., McCoy A.J., and Read R.J. Likelihood-enhanced fast rotation functions. Acta Crystallogr. D Biol. Crystallogr. 60 (2004) 432-438
35. Taylor J.S., Reid T.S., Terry K.L., Casey P.J., and Beese L.S. Structure of mammalian protein geranylgeranyltransferase type-I. EMBO J. 22 (2003) 5963-5974
36. Terry K.L., Casey P.J., and Beese L.S. Conversion of protein farnesyltransferase to a geranylgeranyltransferase. Biochemistry 45 (2006) 9746-9755
37. Thompson J.D., Higgins D.G., and Gibson T.J. CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res. 22 (1994) 4673-4680
38. Tschantz W.R., Furfine E.S., and Casey P.J. Substrate binding is required for release of product from mammalian protein farnesyltransferase. J. Biol. Chem. 272 (1997) 9989-9993
39. Van Voorhis W.C., Rivas K.L., Bendale P., Nallan L., Horney C., Barrett L.K., Bauer K.D., Smart B.P., Ankala S., Hucke O., et al. Efficacy, pharmacokinetics, and metabolism of tetrahydroquinoline inhibitors of Plasmodium falciparum protein farnesyltransferase. Antimicrob. Agents Chemother. 51 (2007) 3659-3671
40. Zhang F.L., and Casey P.J. Influence of metal ions on substrate binding and catalytic activity of mammalian protein geranylgeranyltransferase type-I. Biochem. J. 320 (1996) 925-932