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New developments in probing and targeting protein acylation in malaria, leishmaniasis and African sleeping sickness

Published online by Cambridge University Press:  08 March 2017

MARKUS RITZEFELD
Affiliation:
Department of Chemistry, Imperial College London, London SW7 2AZ, UK
MEGAN H. WRIGHT
Affiliation:
School of Chemistry, University of Leeds, Leeds LS2 9JT, UK
EDWARD W. TATE*
Affiliation:
Department of Chemistry, Imperial College London, London SW7 2AZ, UK
*
*Corresponding author: Department of Chemistry, Imperial College London, London SW7 2AZ, UK. E-mail: e.tate@imperial.ac.uk

Summary

Infections by protozoan parasites, such as Plasmodium falciparum or Leishmania donovani, have a significant health, social and economic impact and threaten billions of people living in tropical and sub-tropical regions of developing countries worldwide. The increasing range of parasite strains resistant to frontline therapeutics makes the identification of novel drug targets and the development of corresponding inhibitors vital. Post-translational modifications (PTMs) are important modulators of biology and inhibition of protein lipidation has emerged as a promising therapeutic strategy for treatment of parasitic diseases. In this review we summarize the latest insights into protein lipidation in protozoan parasites. We discuss how recent chemical proteomic approaches have delivered the first global overviews of protein lipidation in these organisms, contributing to our understanding of the role of this PTM in critical metabolic and cellular functions. Additionally, we highlight the development of new small molecule inhibitors to target parasite acyl transferases.

Type
Special Issue Review
Copyright
Copyright © Cambridge University Press 2017 

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Footnotes

Authors contributed equally to this manuscript.

References

REFERENCES

Alonso, A. M., Coceres, V. M., De Napoli, M. G., Nieto Guil, A. F., Angel, S. O. and Corvi, M. M. (2012). Protein palmitoylation inhibition by 2-bromopalmitate alters gliding, host cell invasion and parasite morphology in Toxoplasma gondii . Molecular and Biochemical Parasitology 184, 3943.CrossRefGoogle ScholarPubMed
Baker, N., de Koning, H. P., Mäser, P. and Horn, D. (2013). Drug resistance in African trypanosomiasis: the melarsoprol and pentamidine story. Trends in Parasitology 29, 110118.Google Scholar
Beck, J. R., Fung, C., Straub, K. W., Coppens, I., Vashisht, A. A., Wohlschlegel, J. A. and Bradley, P. J. (2013). A Toxoplasma palmitoyl acyl transferase and the palmitoylated armadillo repeat protein TgARO govern apical rhoptry tethering and reveal a critical role for the rhoptries in host cell invasion but not egress. PLoS Pathogens 9, e1003162.Google Scholar
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 Tropical Diseases 6, e1625.CrossRefGoogle ScholarPubMed
Bologna, G., Yvon, C., Duvaud, S. and Veuthey, A.-L. (2004). N-Terminal myristoylation predictions by ensembles of neural networks. Proteomics 4, 16261632.CrossRefGoogle ScholarPubMed
Boutin, J. A. (1997). Myristoylation. Cellular Signalling 9, 1535.Google Scholar
Bowyer, P. W., Gunaratne, R. S., Grainger, M., Withers-Martinez, C., Wickramsinghe, S. R., Tate, E. W., Leatherbarrow, R. J., Brown, K. A., Holder, A. A. and Smith, D. F. (2007). Molecules incorporating a benzothiazole core scaffold inhibit the N-myristoyltransferase of Plasmodium falciparum . The Biochemical Journal 408, 173180.CrossRefGoogle ScholarPubMed
Bowyer, P. W., Tate, E. W., Leatherbarrow, R. J., Holder, A. A., Smith, D. F. and Brown, K. A. (2008). N-myristoyltransferase: a prospective drug target for protozoan parasites. ChemMedChem 3, 402408.Google Scholar
Brand, S., Cleghorn, L. A. T., 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. J., Read, K. D., Wyatt, P. G. and Gilbert, I. H. (2012). Discovery of a novel class of orally active trypanocidal N-myristoyltransferase inhibitors. Journal of Medicinal Chemistry 55, 140152.Google Scholar
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. C., van Aalten, D., Frearson, J. A., Brenk, R., Fairlamb, A. H., Ferguson, M. A. J., 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. Journal of Medicinal Chemistry 57, 98559869.Google Scholar
Brannigan, J. A., Roberts, S. M., Bell, A. S., Hutton, J. A., Hodgkinson, M. R., Tate, E. W., Leatherbarrow, R. J., Smith, D. F. and Wilkinson, A. J. (2014). Diverse modes of binding in structures of Leishmania major N-myristoyltransferase with selective inhibitors. IUCrJ 1, 250260.CrossRefGoogle ScholarPubMed
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. Angewandte Chemie International Edition 54, 59485951.Google Scholar
Caballero, M. C., Alonso, A. M., Deng, B., Attias, M., de Souza, W. and Corvi, M. M. (2016). Identification of new palmitoylated proteins in Toxoplasma gondii . Biochimica Et Biophysica Acta 1864, 400408.CrossRefGoogle ScholarPubMed
Child, M. A., Hall, C. I., Beck, J. R., Ofori, L. O., Albrow, V. E., Garland, M., Bowyer, P. W., Bradley, P. J., Powers, J. C., Boothroyd, J. C., Weerapana, E. and Bogyo, M. (2013). Small-molecule inhibition of a depalmitoylase enhances Toxoplasma host-cell invasion. Nature Chemical Biology 9, 651656.Google Scholar
Coleman, R. A., Rao, P., Fogelsong, R. J. and Bardes, E. S. (1992). 2-Bromopalmitoyl-CoA and 2-bromopalmitate: promiscuous inhibitors of membrane-bound enzymes. Biochimica Et Biophysica Acta 1125, 203209.Google Scholar
Davda, D., El Azzouny, M. A., Tom, C. T. M. B., Hernandez, J. L., Majmudar, J. D., Kennedy, R. T. and Martin, B. R. (2013). Profiling targets of the irreversible palmitoylation inhibitor 2-bromopalmitate. ACS Chemical Biology 8, 19121917.Google Scholar
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. Proceedings of the National Academy of Sciences 91, 97359739.Google Scholar
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. Journal of Cell Science 122, 867874.Google Scholar
Emmer, B. T., Nakayasu, E. S., Souther, C., Choi, H., Sobreira, T. J. P., 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, 455463.Google Scholar
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. The Journal of Biological Chemistry 260, 1454714555.Google Scholar
Flegr, J., Prandota, J., Sovičková, M. and Israili, Z. H. (2014). Toxoplasmosis – a global threat. correlation of latent toxoplasmosis with specific disease burden in a set of 88 countries. PLoS ONE 9, 122.CrossRefGoogle Scholar
Foe, I. T., Child, M. A., Majmudar, J. D., Krishnamurthy, S., van der Linden, W. A., Ward, G. E., Martin, B. R. and Bogyo, M. (2015). Global analysis of palmitoylated proteins in Toxoplasma gondii . Cell Host & Microbe 18, 501511.Google Scholar
Forrester, M. T., Hess, D. T., Thompson, J. W., Hultman, R., Moseley, M. A., Stamler, J. S. and Casey, P. J. (2011). Site-specific analysis of protein S-acylation by resin-assisted capture. Journal of Lipid Research 52, 393398.Google Scholar
Frearson, J. A., Brand, S., McElroy, S. P., Cleghorn, L. A. T., Smid, O., Stojanovski, L., Price, H. P., Guther, M. L. S., 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. F., Brenk, R., Gilbert, I. H., Read, K. D., Fairlamb, A. H., Ferguson, M. A. J., Smith, D. F. and Wyatt, P. G. (2010). N-myristoyltransferase inhibitors as new leads to treat sleeping sickness. Nature 464, 728732.Google Scholar
Frénal, K., Tay, C. L., Mueller, C., Bushell, E. S., Jia, Y., Graindorge, A., Billker, O., Rayner, J. C. and Soldati-Favre, D. (2013). Global analysis of apicomplexan protein S-Acyl transferases reveals an enzyme essential for invasion: repertoire of essential PATs in two apicomplexans. Traffic 14, 895911.Google Scholar
Galvin, B. D., Li, Z., Villemaine, E., Poole, C. B., Chapman, M. S., Pollastri, M. P., Wyatt, P. G. and Carlow, C. K. S. (2014). A target repurposing approach identifies N-myristoyltransferase as a new candidate drug target in filarial nematodes. PLoS Neglected Tropical Diseases 8, 113.CrossRefGoogle ScholarPubMed
Godsel, L. M. (1999). Flagellar protein localization mediated by a calcium-myristoyl/palmitoyl switch mechanism. The EMBO Journal 18, 20572065.CrossRefGoogle ScholarPubMed
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 in Parasitology 30, 350360.Google Scholar
Goncalves, V., Brannigan, J. A., Thinon, E., Olaleye, T. O., Serwa, R., Lanzarone, S., Wilkinson, A. J., Tate, E. W. and Leatherbarrow, R. J. (2012 a). A fluorescence-based assay for N-myristoyltransferase activity. Analytical Biochemistry 421, 342344.Google Scholar
Goncalves, V., Brannigan, J. A., Whalley, D., Ansell, K. H., Saxty, B., Holder, A. A., Wilkinson, A. J., Tate, E. W. and Leatherbarrow, R. J. (2012 b). Discovery of Plasmodium vivax N-myristoyltransferase inhibitors: screening, synthesis, and structural characterization of their binding mode. Journal of Medicinal Chemistry 55, 35783582.CrossRefGoogle ScholarPubMed
Graf, F. E., Ludin, P., Arquint, C., Schmidt, R. S., Schaub, N., Kunz Renggli, C., Munday, J. C., Krezdorn, J., Baker, N., Horn, D., Balmer, O., Caccone, A., de Koning, H. P. and Mäser, P. (2016). Comparative genomics of drug resistance in Trypanosoma brucei rhodesiense . Cellular and Molecular Life Sciences: CMLS 73, 33873400.Google Scholar
Gunaratne, R. S., Sajid, M., Ling, I. T., Tripathi, R., Pachebat, J. A. and Holder, A. A. (2000). Characterization of N-myristoyltransferase from Plasmodium falciparum . Biochemical Journal 348, 459463.Google Scholar
Guttery, D. S., Poulin, B., Ramaprasad, A., Wall, R. J., Ferguson, D. J. P., Brady, D., Patzewitz, E.-M., Whipple, S., Straschil, U., Wright, M. H., Mohamed, A. M. A. H., 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, 128140.Google Scholar
Hajjaran, H., Kazemi-Rad, E., Mohebali, M., Oshaghi, M. A., Khadem-Erfan, M. B., Hajaliloo, E., Reisi Nafchi, H. and Raoofian, R. (2016). Expression analysis of activated protein kinase C gene (LACK1) in antimony sensitive and resistant Leishmania tropica clinical isolates using real-time RT-PCR. International Journal of Dermatology 55, 10201026.Google Scholar
Heal, W. P., Wickramasinghe, S. R., Leatherbarrow, R. J. and Tate, E. W. (2008). N-myristoyl transferase-mediated protein labelling in vivo . Organic & Biomolecular Chemistry 6, 23082315.CrossRefGoogle ScholarPubMed
Herrera, L. J., Brand, S., Santos, A., Nohara, L. L., Harrison, J., Norcross, N. R., Thompson, S., Smith, V., Lema, C., Varela-Ramirez, A., Gilbert, I. H., Almeida, I. C. and Maldonado, R. A. (2016). Validation of N-myristoyltransferase as potential chemotherapeutic target in mammal-dwelling stages of Trypanosoma cruzi . PLoS Neglected Tropical Diseases 10, 120.Google Scholar
Hopp, C. S., Balaban, A. E., Bushell, E. S. C., Billker, O., Rayner, J. C. and Sinnis, P. (2016). Palmitoyl transferases have critical roles in the development of mosquito and liver stages of Plasmodium: palmitoyl transferases and mosquito stages of Plasmodium . Cellular Microbiology 18, 16251641.CrossRefGoogle ScholarPubMed
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. Journal of Medicinal Chemistry 57, 86648670.Google Scholar
Jones, J. L., Parise, M. E. and Fiore, A. E. (2014). Neglected parasitic infections in the United States: toxoplasmosis. The American Journal of Tropical Medicine and Hygiene 90, 794799.Google Scholar
Jones, M. L., Collins, M. O., Goulding, D., Choudhary, J. S. and Rayner, J. C. (2012). Analysis of protein palmitoylation reveals a pervasive role in Plasmodium development and pathogenesis. Cell Host & Microbe 12, 246258.CrossRefGoogle ScholarPubMed
Kemp, L. E., Rusch, M., Adibekian, A., Bullen, H. E., Graindorge, A., Freymond, C., Rottmann, M., Braun-Breton, C., Baumeister, S., Porfetye, A. T., Vetter, I. R., Hedberg, C. and Soldati-Favre, D. (2013). Characterization of a serine hydrolase targeted by acyl-protein thioesterase inhibitors in Toxoplasma gondii . The Journal of Biological Chemistry 288, 2700227018.Google Scholar
Keserü, G. M. and Makara, G. M. (2009). The influence of lead discovery strategies on the properties of drug candidates. Nature Reviews Drug Discovery 8, 203212.Google Scholar
Leber, W., Skippen, A., Fivelman, Q. L., Bowyer, P. W., Cockcroft, S. and Baker, D. A. (2009). A unique phosphatidylinositol 4-phosphate 5-kinase is activated by ADP-ribosylation factor in Plasmodium falciparum . International Journal for Parasitology 39, 645653.Google Scholar
Li, Y. F. and Radivojac, P. (2012). Computational approaches to protein inference in shotgun proteomics. BMC Bioinformatics 13 (Suppl. 16), S4.Google Scholar
Maurer-Stroh, S., Eisenhaber, B. and Eisenhaber, F. (2002). N-terminal N-myristoylation of proteins: prediction of substrate proteins from amino acid sequence. Journal of Molecular Biology 317, 541557.Google Scholar
Mbengue, A., Bhattacharjee, S., Pandharkar, T., Liu, H., Estiu, G., Stahelin, R. V., Rizk, S. S., Njimoh, D. L., Ryan, Y., Chotivanich, K., Nguon, C., Ghorbal, M., Lopez-Rubio, J.-J., Pfrender, M., Emrich, S., Mohandas, N., Dondorp, A. M., Wiest, O. and Haldar, K. (2015). A molecular mechanism of artemisinin resistance in Plasmodium falciparum malaria. Nature 520, 683687.Google Scholar
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 . Molecular and Biochemical Parasitology 152, 2234.CrossRefGoogle ScholarPubMed
Möskes, C., Burghaus, P. A., Wernli, B., Sauder, U., Dürrenberger, M. and Kappes, B. (2004). Export of Plasmodium falciparum calcium-dependent protein kinase 1 to the parasitophorous vacuole is dependent on three N-terminal membrane anchor motifs. Molecular Microbiology 54, 676691.Google Scholar
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. Organic & Biomolecular Chemistry 12, 81328137.CrossRefGoogle ScholarPubMed
Paape, D., Bell, A. S., Heal, W. P., Hutton, J. A., Leatherbarrow, R. J., Tate, E. W. and Smith, D. F. (2014). Using a non-image-based medium-throughput assay for screening compounds targeting N-myristoylation in intracellular Leishmania amastigotes. PLoS Neglected Tropical Diseases 8, 110.Google Scholar
Percher, A., Ramakrishnan, S., Thinon, E., Yuan, X., Yount, J. S. and Hang, H. C. (2016). Mass-tag labeling reveals site-specific and endogenous levels of protein S-fatty acylation. Proceedings of the National Academy of Sciences of the United States of America 113, 43024307.Google Scholar
Poulin, B., Patzewitz, E.-M., Brady, D., Silvie, O., Wright, M. H., Ferguson, D. J. P., Wall, R. J., Whipple, S., Guttery, D. S., Tate, E. W., Wickstead, B., Holder, A. A. and Tewari, R. (2013). Unique apicomplexan IMC sub-compartment proteins are early markers for apical polarity in the malaria parasite. Biology Open 2, 11601170.Google Scholar
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. The Journal of Biological Chemistry 278, 72067214.Google Scholar
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 . Biochimica Et Biophysica Acta 1823, 11781191.CrossRefGoogle ScholarPubMed
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. Journal of Biological Chemistry 286, 3991439925.Google Scholar
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. Journal of Medicinal Chemistry 56, 371375.Google Scholar
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). Journal of Medicinal Chemistry 57, 27732788.Google Scholar
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, 17611766.CrossRefGoogle ScholarPubMed
Rahlfs, S., Koncarevic, S., Iozef, R., Mailu, B. M., Savvides, S. N., Schirmer, R. H. and Becker, K. (2009). Myristoylated adenylate kinase-2 of Plasmodium falciparum forms a heterodimer with myristoyltransferase. Molecular and Biochemical Parasitology 163, 7784.CrossRefGoogle ScholarPubMed
Rees-Channer, R. R., Martin, S. R., Green, J. L., Bowyer, P. W., Grainger, M., Molloy, J. E. and Holder, A. A. (2006). Dual acylation of the 45 kDa gliding-associated protein (GAP45) in Plasmodium falciparum merozoites. Molecular and Biochemical Parasitology 149, 113116.Google Scholar
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 Engineering, Design & Selection: PEDS 21, 639644.CrossRefGoogle ScholarPubMed
Resh, M. D. (1999). Fatty acylation of proteins: new insights into membrane targeting of myristoylated and palmitoylated proteins. Biochimica et Biophysica Acta (BBA) – Molecular Cell Research 1451, 116.Google Scholar
Resh, M. D. (2006). Trafficking and signaling by fatty-acylated and prenylated proteins. Nature Chemical Biology 2, 584590.CrossRefGoogle ScholarPubMed
Resh, M. D. (2016). Fatty acylation of proteins: the long and the short of it. Progress in Lipid Research 63, 120131.Google Scholar
Roberts, A. J. and Fairlamb, A. H. (2016). The N-myristoylome of Trypanosoma cruzi . Scientific Reports 6, 31078.CrossRefGoogle ScholarPubMed
Roberts, A. J., Torrie, L. S., Wyllie, S. and Fairlamb, A. H. (2014). Biochemical and genetic characterization of Trypanosoma cruzi N-myristoyltransferase. The Biochemical Journal 459, 323332.Google Scholar
Roth, A. F., Wan, J., Bailey, A. O., Sun, B., Kuchar, J. A., Green, W. N., Phinney, B. S., Yates, J. R. and Davis, N. G. (2006). Global analysis of protein palmitoylation in yeast. Cell 125, 10031013.Google Scholar
Sádlová, J., Price, H. P., Smith, B. A., Votýpka, J., Volf, P. and Smith, D. F. (2010). The stage-regulated HASPB and SHERP proteins are essential for differentiation of the protozoan parasite Leishmania major in its sand fly vector, Phlebotomus papatasi . Cellular Microbiology 12, 17651779.Google Scholar
Sahin, A., Espiau, B., Tetaud, E., Cuvillier, A., Lartigue, L., Ambit, A., Robinson, D. R. and Merlin, G. (2008). The Leishmania ARL-1 and Golgi Traffic. PLOS ONE 3, e1620.Google Scholar
Santos, J. M., Duarte, N., Kehrer, J., Ramesar, J., Avramut, M. C., Koster, A. J., Dessens, J. T., Frischknecht, F., Chevalley-Maurel, S., Janse, C. J., Franke-Fayard, B. and Mair, G. R. (2016). Maternally supplied S-acyl-transferase is required for crystalloid organelle formation and transmission of the malaria parasite. Proceedings of the National Academy of Sciences 113, 71837188.Google Scholar
Sinha, S., Medhi, B. and Sehgal, R. (2014). Challenges of drug-resistant malaria. Parasite 21, 115.Google Scholar
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, 18211836.Google Scholar
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, 3749.Google Scholar
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. Current Opinion in Chemical Biology 24, 4857.Google Scholar
Tay, C. L., Jones, M. L., Hodson, N., Theron, M., Choudhary, J. S. and Rayner, J. C. (2016). Study of Plasmodium falciparum DHHC palmitoyl transferases identifies a role for PfDHHC9 in gametocytogenesis: study of Plasmodium falciparum DHHC palmitoyl transferases. Cellular Microbiology 18, 15961610.Google Scholar
World Health Organization (2015). World malaria report. World Health Organization, Geneva, Switzerland.Google Scholar
World Health Organization (2016 a). Leishmaniasis Fact Sheet No. 375. World Health Organization, Geneva, Switzerland.Google Scholar
World Health Organization (2016 b). Trypanosomiasis Fact Sheet No. 259. World Health Organization, Geneva, Switzerland.Google Scholar
Wilcox, C., Hu, J. S. and Olson, E. N. (1987). Acylation of proteins with myristic acid occurs cotranslationally. Science 238, 12751278.Google Scholar
Wright, M. H., Heal, W. P., Mann, D. J. and Tate, E. W. (2009). Protein myristoylation in health and disease. Journal of Chemical Biology 3, 1935.Google Scholar
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. Nature Chemistry 6, 112121.Google Scholar
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 . Chemistry & Biology 22, 342354.Google Scholar
Wright, M. H., Paape, D., Price, H. P., Smith, D. F. and Tate, E. W. (2016). Global profiling and inhibition of protein lipidation in vector and host stages of the sleeping sickness parasite Trypanosoma brucei . ACS Infectious Diseases 2, 427441.Google Scholar
Yu, Z., Brannigan, J. A., Moss, D. K., Brzozowski, A. M., Wilkinson, A. J., Holder, A. A., Tate, E. W. and Leatherbarrow, R. J. (2012). Design and synthesis of inhibitors of Plasmodium falciparum N-myristoyltransferase, a promising target for antimalarial drug discovery. Journal of Medicinal Chemistry 55, 88798890.Google Scholar
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, 17671772.Google Scholar
Zheng, B., DeRan, M., Li, X., Liao, X., Fukata, M. and Wu, X. (2013). 2-bromopalmitate analogues as activity-based probes to explore palmitoyl acyltransferases. Journal of the American Chemical Society 135, 70827085.CrossRefGoogle ScholarPubMed
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