Global profiling and inhibition of protein lipidation in vector and host stages of the sleeping sickness parasite trypanosoma brucei

ACS Infectious Diseases

Volumn 2, Issue 6, 2016, Pages 427-441

  Wright, Megan H ^a,c   Paape, Daniel ^b,d   Price, Helen P ^b,e   Smith, Deborah F ^b   Tate, Edward W ^a  

^a IMPERIAL COLLEGE LONDON   (United Kingdom)

^b UNIVERSITY OF YORK   (United Kingdom)

^c TECHNICAL UNIVERSITY OF MUNICH   (Germany)

^d UNIVERSITY OF GLASGOW   (United Kingdom)

^e KEELE UNIVERSITY   (United Kingdom)

Author keywords

chemical proteomics; click chemistry; human African trypanosomiasis; N myristoylation; protein lipidation; target validation

Indexed keywords

ALKYNE; CALPAIN; GUANOSINE TRIPHOSPHATASE; MYRISTIC ACID DERIVATIVE; PALMITIC ACID; PHOSPHATASE; PROTEIN N MYRISTOYLTRANSFERASE; PROTEIN N MYRISTOYLTRANSFERASE INHIBITOR;

ACYLATION; AFRICAN TRYPANOSOMIASIS; ARTICLE; HOST; INSECT; LIFE CYCLE STAGE; NONHUMAN; PARASITE CULTIVATION; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN MODIFICATION; PROTEOMICS; TRYPANOSOMA BRUCEI;

EID: 85006216638     PISSN: None     EISSN: 23738227     Source Type: Journal    
DOI: 10.1021/acsinfecdis.6b00034     Document Type: Article

References (75)

1. Simarro, P. P., Diarra, A., Ruiz Postigo, J. A., Franco, J. R., and Jannin, J. G. (2011) The human African trypanosomiasis control and surveillance programme of the World Health Organization 2000-2009: the way forward PLoS Neglected Trop. Dis. 5 (2) e1007 10.1371/journal.pntd.0001007
2. Simarro, P. P., Cecchi, G., Franco, J. R., Paone, M., Diarra, A., Ruiz-Postigo, J. A., Fevre, E. M., Mattioli, R. C., and Jannin, J. G. (2012) Estimating and mapping the population at risk of sleeping sickness PLoS Neglected Trop. Dis. 6 (10) e1859 10.1371/journal.pntd.0001859
3. Cecchi, G. and Mattioli, R. C. (2009) Global Geospatial Datasets for African Trypanosomiasis Management: A Review, pp 1-39, FAO, Rome, Italy.
4. Nagle, A. S., Khare, S., Kumar, A. B., Supek, F., Buchynskyy, A., Mathison, C. J., Chennamaneni, N. K., Pendem, N., Buckner, F. S., Gelb, M. H., and Molteni, V. (2014) Recent developments in drug discovery for leishmaniasis and human African trypanosomiasis Chem. Rev. 114 (22) 11305-11347 10.1021/cr500365f
5. Lee, S. H., Stephens, J. L., and Englund, P. T. (2007) A fatty-acid synthesis mechanism specialized for parasitism Nat. Rev. Microbiol. 5 (4) 287-297 10.1038/nrmicro1617
6. Wright, M. H., Heal, W. P., Mann, D. J., and Tate, E. W. (2010) Protein myristoylation in health and disease J. Chem. Biol. 3 (1) 19-35 10.1007/s12154-009-0032-8
7. Frearson, J. A., Brand, S., McElroy, S. P., Cleghorn, L. A., Smid, O., Stojanovski, L., Price, H. P., Guther, M. L., Torrie, L. S., Robinson, D. A., Hallyburton, I., Mpamhanga, C. P., Brannigan, J. A., Wilkinson, A. J., Hodgkinson, M., Hui, R., Qiu, W., Raimi, O. G., van Aalten, D. M., Brenk, R., Gilbert, I. H., Read, K. D., Fairlamb, A. H., Ferguson, M. A., Smith, D. F., and Wyatt, P. G. (2010) N-myristoyltransferase inhibitors as new leads to treat sleeping sickness Nature 464 (7289) 728-732 10.1038/nature08893
8. Georgopapadakou, N. H. (2002) Antifungals targeted to protein modification: focus on protein N-myristoyltransferase Expert Opin. Invest. Drugs 11 (8) 1117-1125 10.1517/13543784.11.8.1117
9. Brannigan, J. A., Smith, B. A., Yu, Z., Brzozowski, A. M., Hodgkinson, M. R., Maroof, A., Price, H. P., Meier, F., Leatherbarrow, R. J., Tate, E. W., Smith, D. F., and Wilkinson, A. J. (2010) N-Myristoyltransferase from Leishmania donovani: structural and functional characterisation of a potential drug target for visceral leishmaniasis J. Mol. Biol. 396 (4) 985-999 10.1016/j.jmb.2009.12.032
10. Tate, E. W., Bell, A. S., Rackham, M. D., and Wright, M. H. (2014) N-Myristoyltransferase as a potential drug target in malaria and leishmaniasis Parasitology 141 (1) 37-49 10.1017/S0031182013000450
11. Wright, M. H., Clough, B., Rackham, M. D., Rangachari, K., Brannigan, J. A., Grainger, M., Moss, D. K., Bottrill, A. R., Heal, W. P., Broncel, M., Serwa, R. A., Brady, D., Mann, D. J., Leatherbarrow, R. J., Tewari, R., Wilkinson, A. J., Holder, A. A., and Tate, E. W. (2014) Validation of N-myristoyltransferase as an antimalarial drug target using an integrated chemical biology approach Nat. Chem. 6 (2) 112-121 10.1038/nchem.1830
12. Galvin, B. D., Li, Z., Villemaine, E., Poole, C. B., Chapman, M. S., Pollastri, M. P., Wyatt, P. G., and Carlow, C. K. (2014) A target repurposing approach identifies N-myristoyltransferase as a new candidate drug target in filarial nematodes PLoS Neglected Trop. Dis. 8 (9) e3145 10.1371/journal.pntd.0003145
13. Thinon, E., Serwa, R. A., Broncel, M., Brannigan, J. A., Brassat, U., Wright, M. H., Heal, W. P., Wilkinson, A. J., Mann, D. J., and Tate, E. W. (2014) Global profiling of co- and post-translationally N-myristoylated proteomes in human cells Nat. Commun. 5, 4919 10.1038/ncomms5919
14. Brand, S., Cleghorn, L. A., McElroy, S. P., Robinson, D. A., Smith, V. C., Hallyburton, I., Harrison, J. R., Norcross, N. R., Spinks, D., Bayliss, T., Norval, S., Stojanovski, L., Torrie, L. S., Frearson, J. A., Brenk, R., Fairlamb, A. H., Ferguson, M. A., Read, K. D., Wyatt, P. G., and Gilbert, I. H. (2012) Discovery of a novel class of orally active trypanocidal N-myristoyltransferase inhibitors J. Med. Chem. 55 (1) 140-152 10.1021/jm201091t
15. Brand, S., Norcross, N. R., Thompson, S., Harrison, J. R., Smith, V. C., Robinson, D. A., Torrie, L. S., McElroy, S. P., Hallyburton, I., Norval, S., Scullion, P., Stojanovski, L., Simeons, F. R., van Aalten, D., Frearson, J. A., Brenk, R., Fairlamb, A. H., Ferguson, M. A., Wyatt, P. G., Gilbert, I. H., and Read, K. D. (2014) Lead optimization of a pyrazole sulfonamide series of Trypanosoma brucei N-myristoyltransferase inhibitors: identification and evaluation of CNS penetrant compounds as potential treatments for stage 2 human African trypanosomiasis J. Med. Chem. 57 (23) 9855-9869 10.1021/jm500809c
16. Spinks, D., Smith, V., Thompson, S., Robinson, D. A., Luksch, T., Smith, A., Torrie, L. S., McElroy, S., Stojanovski, L., Norval, S., Collie, I. T., Hallyburton, I., Rao, B., Brand, S., Brenk, R., Frearson, J. A., Read, K. D., Wyatt, P. G., and Gilbert, I. H. (2015) Development of Small-Molecule Trypanosoma brucei N-Myristoyltransferase Inhibitors: Discovery and Optimisation of a Novel Binding Mode ChemMedChem 10 (11) 1821-1836 10.1002/cmdc.201500301
17. Bell, A. S., Mills, J. E., Williams, G. P., Brannigan, J. A., Wilkinson, A. J., Parkinson, T., Leatherbarrow, R. J., Tate, E. W., Holder, A. A., and Smith, D. F. (2012) Selective Inhibitors of Protozoan Protein N-myristoyltransferases as Starting Points for Tropical Disease Medicinal Chemistry Programs PLoS Neglected Trop. Dis. 6 (4) e1625 10.1371/journal.pntd.0001625
18. Hutton, J. A., Goncalves, V., Brannigan, J. A., Paape, D., Wright, M. H., Waugh, T. M., Roberts, S. M., Bell, A. S., Wilkinson, A. J., Smith, D. F., Leatherbarrow, R. J., and Tate, E. W. (2014) Structure-Based Design of Potent and Selective Leishmania N-Myristoyltransferase Inhibitors J. Med. Chem. 57 (20) 8664-8670 10.1021/jm5011397
19. Rackham, M. D., Brannigan, J. A., Moss, D. K., Yu, Z., Wilkinson, A. J., Holder, A. A., Tate, E. W., and Leatherbarrow, R. J. (2013) Discovery of novel and ligand-efficient inhibitors of Plasmodium falciparum and Plasmodium vivax N-myristoyltransferase J. Med. Chem. 56 (1) 371-375 10.1021/jm301474t
20. Olaleye, T. O., Brannigan, J. A., Roberts, S. M., Leatherbarrow, R. J., Wilkinson, A. J., and Tate, E. W. (2014) Peptidomimetic inhibitors of N-myristoyltransferase from human malaria and leishmaniasis parasites Org. Biomol. Chem. 12 (41) 8132-8137 10.1039/C4OB01669F
21. Rackham, M. D., Brannigan, J. A., Rangachari, K., Meister, S., Wilkinson, A. J., Holder, A. A., Leatherbarrow, R. J., and Tate, E. W. (2014) Design and synthesis of high affinity inhibitors of Plasmodium falciparum and Plasmodium vivax N-myristoyltransferases directed by ligand efficiency dependent lipophilicity (LELP) J. Med. Chem. 57 (6) 2773-2788 10.1021/jm500066b
22. Rackham, M. D., Yu, Z., Brannigan, J. A., Heal, W. P., Paape, D., Barker, K. V., Wilkinson, A. J., Smith, D. F., Leatherbarrow, R. J., and Tate, E. W. (2015) Discovery of high affinity inhibitors of Leishmania donovani N-myristoyltransferase MedChemComm 6 (10) 1761-1766 10.1039/C5MD00241A
23. Yu, Z., Brannigan, J. A., Rangachari, K., Heal, W. P., Wilkinson, A. J., Holder, A. A., Leatherbarrow, R. J., and Tate, E. W. (2015) Discovery of pyridyl-based inhibitors of Plasmodium falciparum N-myristoyltransferase MedChemComm 6 (10) 1767-1772 10.1039/C5MD00242G
24. Price, H. P., Guther, M. L., Ferguson, M. A., and Smith, D. F. (2010) Myristoyl-CoA:protein N-myristoyltransferase depletion in trypanosomes causes avirulence and endocytic defects Mol. Biochem. Parasitol. 169 (1) 55-58 10.1016/j.molbiopara.2009.09.006
25. Price, H. P., Menon, M. R., Panethymitaki, C., Goulding, D., McKean, P. G., and Smith, D. F. (2003) Myristoyl-CoA:protein N-myristoyltransferase, an essential enzyme and potential drug target in kinetoplastid parasites J. Biol. Chem. 278 (9) 7206-7214 10.1074/jbc.M211391200
26. Price, H. P., Goulding, D., and Smith, D. F. (2005) ARL1 has an essential role in Trypanosoma brucei Biochem. Soc. Trans. 33 (4) 643-645 10.1042/BST0330643
27. Price, H. P., Stark, M., and Smith, D. F. (2007) Trypanosoma brucei ARF1 plays a central role in endocytosis and golgi-lysosome trafficking Mol. Biol. Cell 18 (3) 864-873 10.1091/mbc.E06-08-0736
28. Price, H. P., Panethymitaki, C., Goulding, D., and Smith, D. F. (2005) Functional analysis of TbARL1, an N-myristoylated Golgi protein essential for viability in bloodstream trypanosomes J. Cell Sci. 118 (4) 831-841 10.1242/jcs.01624
29. Mills, E., Price, H. P., Johner, A., Emerson, J. E., and Smith, D. F. (2007) Kinetoplastid PPEF phosphatases: dual acylated proteins expressed in the endomembrane system of Leishmania Mol. Biochem. Parasitol. 152 (1) 22-34 10.1016/j.molbiopara.2006.11.008
30. Price, H. P., Hodgkinson, M. R., Wright, M. H., Tate, E. W., Smith, B. A., Carrington, M., Stark, M., and Smith, D. F. (2012) A role for the vesicle-associated tubulin binding protein ARL6 (BBS3) in flagellum extension in Trypanosoma brucei Biochim. Biophys. Acta, Mol. Cell Res. 1823 (7) 1178-1191 10.1016/j.bbamcr.2012.05.007
31. Hertz-Fowler, C., Ersfeld, K., and Gull, K. (2001) CAP5.5, a life-cycle-regulated, cytoskeleton-associated protein is a member of a novel family of calpain-related proteins in Trypanosoma brucei Mol. Biochem. Parasitol. 116 (1) 25-34 10.1016/S0166-6851(01)00296-1
32. Emmer, B. T., Souther, C., Toriello, K. M., Olson, C. L., Epting, C. L., and Engman, D. M. (2009) Identification of a palmitoyl acyltransferase required for protein sorting to the flagellar membrane J. Cell Sci. 122 (6) 867-874 10.1242/jcs.041764
33. Godsel, L. M. and Engman, D. M. (1999) Flagellar protein localization mediated by a calcium-myristoyl/palmitoyl switch mechanism EMBO J. 18 (8) 2057-2065 10.1093/emboj/18.8.2057
34. Proto, W. R., Castanys-Munoz, E., Black, A., Tetley, L., Moss, C. X., Juliano, L., Coombs, G. H., and Mottram, J. C. (2011) Trypanosoma brucei metacaspase 4 is a pseudopeptidase and a virulence factor J. Biol. Chem. 286 (46) 39914-39925 10.1074/jbc.M111.292334
35. Tate, E. W., Kalesh, K. A., Lanyon-Hogg, T., Storck, E. M., and Thinon, E. (2015) Global profiling of protein lipidation using chemical proteomic technologies Curr. Opin. Chem. Biol. 24, 48-57 10.1016/j.cbpa.2014.10.016
36. Peng, T., Thinon, E., and Hang, H. C. (2016) Proteomic analysis of fatty-acylated proteins Curr. Opin. Chem. Biol. 30, 77-86 10.1016/j.cbpa.2015.11.008
37. Wright, M. H., Paape, D., Storck, E. M., Serwa, R. A., Smith, D. F., and Tate, E. W. (2015) Global analysis of protein N-myristoylation and exploration of N-myristoyltransferase as a drug target in the neglected human pathogen Leishmania donovani Chem. Biol. 22 (3) 342-354 10.1016/j.chembiol.2015.01.003
38. Serwa, R. A., Abaitua, F., Krause, E., Tate, E. W., and O'Hare, P. (2015) Systems Analysis of Protein Fatty Acylation in Herpes Simplex Virus-Infected Cells Using Chemical Proteomics Chem. Biol. 22 (8) 1008-1017 10.1016/j.chembiol.2015.06.024
39. Broncel, M., Serwa, R. A., Ciepla, P., Krause, E., Dallman, M. J., Magee, A. I., and Tate, E. W. (2015) Multifunctional reagents for quantitative proteome-wide analysis of protein modification in human cells and dynamic profiling of protein lipidation during vertebrate development Angew. Chem., Int. Ed. 54 (20) 5948-5951 10.1002/anie.201500342
40. Heal, W. P., Wright, M. H., Thinon, E., and Tate, E. W. (2012) Multifunctional protein labeling via enzymatic N-terminal tagging and elaboration by click chemistry Nat. Protoc. 7 (1) 105-117 10.1038/nprot.2011.425
41. Treumann, A., Zitzmann, N., Hulsmeier, A., Prescott, A. R., Almond, A., Sheehan, J., and Ferguson, M. A. (1997) Structural characterisation of two forms of procyclic acidic repetitive protein expressed by procyclic forms of Trypanosoma brucei J. Mol. Biol. 269 (4) 529-547 10.1006/jmbi.1997.1066
42. Vassella, E., Butikofer, P., Engstler, M., Jelk, J., and Roditi, I. (2003) Procyclin null mutants of Trypanosoma brucei express free glycosylphosphatidylinositols on their surface Mol. Biol. Cell 14 (4) 1308-1318 10.1091/mbc.E02-10-0694
43. Butikofer, P., Ruepp, S., Boschung, M., and Roditi, I. (1997) 'GPEET' procyclin is the major surface protein of procyclic culture forms of Trypanosoma brucei brucei strain 427 Biochem. J. 326 (2) 415-423 10.1042/bj3260415
44. Allen, C. L., Goulding, D., and Field, M. C. (2003) Clathrin-mediated endocytosis is essential in Trypanosoma brucei EMBO J. 22 (19) 4991-5002 10.1093/emboj/cdg481
45. Doering, T. L., Lu, T., Werbovetz, K. A., Gokel, G. W., Hart, G. W., Gordon, J. I., and Englund, P. T. (1994) Toxicity of myristic acid analogs toward African trypanosomes Proc. Natl. Acad. Sci. U.S.A. 91 (21) 9735-9739 10.1073/pnas.91.21.9735
46. Ferguson, M. A., Low, M. G., and Cross, G. A. (1985) Glycosyl-sn-1,2-dimyristylphosphatidylinositol is covalently linked to Trypanosoma brucei variant surface glycoprotein J. Biol. Chem. 260 (27) 14547-14555
47. Cox, J. and Mann, M. (2008) MaxQuant enables high peptide identification rates, individualized p.p.b.-range mass accuracies and proteome-wide protein quantification Nat. Biotechnol. 26 (12) 1367-1372 10.1038/nbt.1511
48. Aslett, M., Aurrecoechea, C., Berriman, M., Brestelli, J., Brunk, B. P., Carrington, M., Depledge, D. P., Fischer, S., Gajria, B., Gao, X., Gardner, M. J., Gingle, A., Grant, G., Harb, O. S., Heiges, M., Hertz-Fowler, C., Houston, R., Innamorato, F., Iodice, J., Kissinger, J. C., Kraemer, E., Li, W., Logan, F. J., Miller, J. A., Mitra, S., Myler, P. J., Nayak, V., Pennington, C., Phan, I., Pinney, D. F., Ramasamy, G., Rogers, M. B., Roos, D. S., Ross, C., Sivam, D., Smith, D. F., Srinivasamoorthy, G., Stoeckert, C. J., Jr., Subramanian, S., Thibodeau, R., Tivey, A., Treatman, C., Velarde, G., and Wang, H. (2010) TriTrypDB: a functional genomic resource for the Trypanosomatidae Nucleic Acids Res. 38 (database issue) D457-D462 10.1093/nar/gkp851
49. Cox, J., Hein, M. Y., Luber, C. A., Paron, I., Nagaraj, N., and Mann, M. (2014) Accurate Proteome-wide Label-free Quantification by Delayed Normalization and Maximal Peptide Ratio Extraction, Termed MaxLFQ Mol. Cell. Proteomics 13 (9) 2513-2526 10.1074/mcp.M113.031591
50. Maurer-Stroh, S., Eisenhaber, B., and Eisenhaber, F. (2002) N-terminal N-myristoylation of proteins: prediction of substrate proteins from amino acid sequence J. Mol. Biol. 317 (4) 541-557 10.1006/jmbi.2002.5426
51. Armah, D. A. and Mensa-Wilmot, K. (1999) S-Myristoylation of a glycosylphosphatidylinositol-specific phospholipase C in Trypanosoma brucei J. Biol. Chem. 274 (9) 5931-5938 10.1074/jbc.274.9.5931
52. Kimura, A., Kato, Y., and Hirano, H. (2012) N-myristoylation of the Rpt2 subunit regulates intracellular localization of the yeast 26S proteasome Biochemistry 51 (44) 8856-8866 10.1021/bi3007862
53. Struck, N. S., de Souza Dias, S., Langer, C., Marti, M., Pearce, J. A., Cowman, A. F., and Gilberger, T. W. (2005) Re-defining the Golgi complex in Plasmodium falciparum using the novel Golgi marker PfGRASP J. Cell Sci. 118 (23) 5603-5613 10.1242/jcs.02673
54. Butter, F., Bucerius, F., Michel, M., Cicova, Z., Mann, M., and Janzen, C. J. (2013) Comparative proteomics of two life cycle stages of stable isotope-labeled Trypanosoma brucei reveals novel components of the parasite's host adaptation machinery Mol. Cell. Proteomics 12 (1) 172-179 10.1074/mcp.M112.019224
55. Urbaniak, M. D., Guther, M. L., and Ferguson, M. A. (2012) Comparative SILAC proteomic analysis of Trypanosoma brucei bloodstream and procyclic lifecycle stages PLoS One 7 (5) e36619 10.1371/journal.pone.0036619
56. Saada, E. A., Kabututu, Z. P., Lopez, M., Shimogawa, M. M., Langousis, G., Oberholzer, M., Riestra, A., Jonsson, Z. O., Wohlschlegel, J. A., and Hill, K. L. (2014) Insect stage-specific receptor adenylate cyclases are localized to distinct subdomains of the Trypanosoma brucei flagellar membrane Eukaryotic Cell 13 (8) 1064-1076 10.1128/EC.00019-14
57. Liu, W., Apagyi, K., McLeavy, L., and Ersfeld, K. (2010) Expression and cellular localisation of calpain-like proteins in Trypanosoma brucei Mol. Biochem. Parasitol. 169 (1) 20-26 10.1016/j.molbiopara.2009.09.004
58. Urbaniak, M. D., Martin, D. M., and Ferguson, M. A. (2013) Global quantitative SILAC phosphoproteomics reveals differential phosphorylation is widespread between the procyclic and bloodstream form lifecycle stages of Trypanosoma brucei J. Proteome Res. 12 (5) 2233-2244 10.1021/pr400086y
59. Guttery, D. S., Poulin, B., Ramaprasad, A., Wall, R. J., Ferguson, D. J., Brady, D., Patzewitz, E. M., Whipple, S., Straschil, U., Wright, M. H., Mohamed, A. M., Radhakrishnan, A., Arold, S. T., Tate, E. W., Holder, A. A., Wickstead, B., Pain, A., and Tewari, R. (2014) Genome-wide functional analysis of Plasmodium protein phosphatases reveals key regulators of parasite development and differentiation Cell Host Microbe 16 (1) 128-140 10.1016/j.chom.2014.05.020
60. Dejung, M., Subota, I., Bucerius, F., Dindar, G., Freiwald, A., Engstler, M., Boshart, M., Butter, F., and Janzen, C. J. (2016) Quantitative Proteomics Uncovers Novel Factors Involved in Developmental Differentiation of Trypanosoma brucei PLoS Pathog. 12 (2) e1005439 10.1371/journal.ppat.1005439
61. Goldston, A. M., Sharma, A. I., Paul, K. S., and Engman, D. M. (2014) Acylation in trypanosomatids: an essential process and potential drug target Trends Parasitol. 30 (7) 350-360 10.1016/j.pt.2014.05.003
62. Charron, G., Zhang, M. M., Yount, J. S., Wilson, J., Raghavan, A. S., Shamir, E., and Hang, H. C. (2009) Robust fluorescent detection of protein fatty-acylation with chemical reporters J. Am. Chem. Soc. 131 (13) 4967-4975 10.1021/ja810122f
63. Lee, S. H., Stephens, J. L., Paul, K. S., and Englund, P. T. (2006) Fatty acid synthesis by elongases in trypanosomes Cell 126 (4) 691-699 10.1016/j.cell.2006.06.045
64. Emmer, B. T., Nakayasu, E. S., Souther, C., Choi, H., Sobreira, T. J., Epting, C. L., Nesvizhskii, A. I., Almeida, I. C., and Engman, D. M. (2011) Global analysis of protein palmitoylation in African trypanosomes Eukaryotic Cell 10 (3) 455-463 10.1128/EC.00248-10
65. Tull, D., Vince, J. E., Callaghan, J. M., Naderer, T., Spurck, T., McFadden, G. I., Currie, G., Ferguson, K., Bacic, A., and McConville, M. J. (2004) SMP-1, a member of a new family of small myristoylated proteins in kinetoplastid parasites, is targeted to the flagellum membrane in Leishmania Mol. Biol. Cell 15 (11) 4775-4786 10.1091/mbc.E04-06-0457
66. Ren, J., Wen, L., Gao, X., Jin, C., Xue, Y., and Yao, X. (2008) CSS-Palm 2.0: an updated software for palmitoylation sites prediction Protein Eng., Des. Sel. 21 (11) 639-644 10.1093/protein/gzn039
67. Masterson, W. J., Raper, J., Doering, T. L., Hart, G. W., and Englund, P. T. (1990) Fatty acid remodeling: a novel reaction sequence in the biosynthesis of trypanosome glycosyl phosphatidylinositol membrane anchors Cell 62 (1) 73-80 10.1016/0092-8674(90)90241-6
68. Doering, T. L., Pessin, M. S., Hoff, E. F., Hart, G. W., Raben, D. M., and Englund, P. T. (1993) Trypanosome metabolism of myristate, the fatty acid required for the variant surface glycoprotein membrane anchor J. Biol. Chem. 268 (13) 9215-9222
69. Roberts, A. J., Torrie, L. S., Wyllie, S., and Fairlamb, A. H. (2014) Biochemical and genetic characterization of Trypanosoma cruzi N-myristoyltransferase Biochem. J. 459 (2) 323-332 10.1042/BJ20131033
70. Brand, S. and Wyatt, P. (2010) N-Myristoyl transferase inhibitors. WO2010026365 A1.
71. Bologna, G., Yvon, C., Duvaud, S., and Veuthey, A. L. (2004) N-Terminal myristoylation predictions by ensembles of neural networks Proteomics 4 (6) 1626-1632 10.1002/pmic.200300783
72. Alsford, S., Turner, D. J., Obado, S. O., Sanchez-Flores, A., Glover, L., Berriman, M., Hertz-Fowler, C., and Horn, D. (2011) High-throughput phenotyping using parallel sequencing of RNA interference targets in the African trypanosome Genome Res. 21 (6) 915-924 10.1101/gr.115089.110
73. Heal, W. P., Jovanovic, B., Bessin, S., Wright, M. H., Magee, A. I., and Tate, E. W. (2011) Bioorthogonal chemical tagging of protein cholesterylation in living cells Chem. Commun. (Cambridge, U. K.) 47 (14) 4081-4083 10.1039/c0cc04710d
74. Wirtz, E., Leal, S., Ochatt, C., and Cross, G. A. (1999) A tightly regulated inducible expression system for conditional gene knock-outs and dominant-negative genetics in Trypanosoma brucei Mol. Biochem. Parasitol. 99 (1) 89-101 10.1016/S0166-6851(99)00002-X
75. Vizcaino, J. A., Cote, R. G., Csordas, A., Dianes, J. A., Fabregat, A., Foster, J. M., Griss, J., Alpi, E., Birim, M., Contell, J., O'Kelly, G., Schoenegger, A., Ovelleiro, D., Perez-Riverol, Y., Reisinger, F., Rios, D., Wang, R., and Hermjakob, H. (2013) The PRoteomics IDEntifications (PRIDE) database and associated tools: status in 2013 Nucleic Acids Res. 41 (database issue) D1063-D1069 10.1093/nar/gks1262