{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T03:09:19Z","timestamp":1793761759722,"version":"4.6.1"},"reference-count":111,"publisher":"Cambridge University Press (CUP)","issue":"1","license":[{"start":{"date-parts":[[2013,4,24]],"date-time":"2013-04-24T00:00:00Z","timestamp":1366761600000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":["journals.cambridge.org"],"crossmark-restriction":true},"short-container-title":["Parasitology"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:title>SUMMARY<\/jats:title><jats:p>Infections caused by protozoan parasites are among the most widespread and intractable transmissible diseases affecting the developing world, with malaria and leishmaniasis being the most costly in terms of morbidity and mortality. Although new drugs are urgently required against both diseases in the face of ever-rising resistance to frontline therapies, very few candidates passing through development pipelines possess a known and novel mode of action. Set in the context of drugs currently in use and under development, we present the evidence for<jats:italic>N<\/jats:italic>-myristoyltransferase (NMT), an enzyme that<jats:italic>N<\/jats:italic>-terminally lipidates a wide range of specific target proteins through post-translational modification, as a potential drug target in malaria and the leishmaniases. We discuss the limitations of current knowledge regarding the downstream targets of this enzyme in protozoa, and our recent progress towards potent cell-active NMT inhibitors against the most clinically-relevant species of parasite. Finally, we outline the next steps required in terms of both tools to understand<jats:italic>N<\/jats:italic>-myristoylation in protozoan parasites, and the generation of potential development candidates based on the output of our recently-reported high-throughput screens.<\/jats:p>","DOI":"10.1017\/s0031182013000450","type":"journal-article","created":{"date-parts":[[2013,4,24]],"date-time":"2013-04-24T08:13:37Z","timestamp":1366791217000},"page":"37-49","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":70,"title":["<i>N-<\/i>Myristoyltransferase as a potential drug target in malaria and leishmaniasis"],"prefix":"10.1017","volume":"141","author":[{"given":"EDWARD W.","family":"TATE","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ANDREW S.","family":"BELL","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MARK D.","family":"RACKHAM","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MEGAN H.","family":"WRIGHT","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"56","published-online":{"date-parts":[[2013,4,24]]},"reference":[{"key":"S0031182013000450_ref105","doi-asserted-by":"publisher","DOI":"10.1038\/nsb0398-213"},{"key":"S0031182013000450_ref103","doi-asserted-by":"publisher","DOI":"10.1038\/nature02779"},{"key":"S0031182013000450_ref95","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.02673"},{"key":"S0031182013000450_ref28","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.11.8.1117"},{"key":"S0031182013000450_ref93","doi-asserted-by":"publisher","DOI":"10.1039\/c2md00277a"},{"key":"S0031182013000450_ref63","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201001026"},{"key":"S0031182013000450_ref109","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3003326"},{"key":"S0031182013000450_ref89","doi-asserted-by":"publisher","DOI":"10.1111\/j.1462-5822.2010.01507.x"},{"key":"S0031182013000450_ref88","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0806926106"},{"key":"S0031182013000450_ref87","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2009.06639.x"},{"key":"S0031182013000450_ref65","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20051886"},{"key":"S0031182013000450_ref82","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0033845"},{"key":"S0031182013000450_ref94","doi-asserted-by":"publisher","DOI":"10.1007\/BF03256811"},{"key":"S0031182013000450_ref80","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio834"},{"key":"S0031182013000450_ref79","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90104-X"},{"key":"S0031182013000450_ref68","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0802982105"},{"key":"S0031182013000450_ref77","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2008.09.008"},{"key":"S0031182013000450_ref74","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0b013e32832f14c1"},{"key":"S0031182013000450_ref67","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.10.016"},{"key":"S0031182013000450_ref60","doi-asserted-by":"publisher","DOI":"10.1358\/dof.2003.028.02.715958"},{"key":"S0031182013000450_ref57","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2958.2004.04313.x"},{"key":"S0031182013000450_ref56","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2006.11.008"},{"key":"S0031182013000450_ref16","doi-asserted-by":"crossref","first-page":"2065","DOI":"10.1242\/jcs.113.11.2065","article-title":"LdARL-3A, a Leishmania promastigote-specific ADP-ribosylation factor-like protein, is essential for flagellum integrity","volume":"113","author":"Cuvillier","year":"2000","journal-title":"Journal of Cell Science"},{"key":"S0031182013000450_ref100","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2011.12.004"},{"key":"S0031182013000450_ref55","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.08.024"},{"key":"S0031182013000450_ref69","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M211391200"},{"key":"S0031182013000450_ref54","doi-asserted-by":"publisher","DOI":"10.1126\/science.1211936"},{"key":"S0031182013000450_ref52","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2002.5426"},{"key":"S0031182013000450_ref50","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200701191"},{"key":"S0031182013000450_ref14","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1015762108"},{"key":"S0031182013000450_ref41","doi-asserted-by":"publisher","DOI":"10.1126\/science.1184785"},{"key":"S0031182013000450_ref40","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.06.005"},{"key":"S0031182013000450_ref37","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(01)00296-1"},{"key":"S0031182013000450_ref35","doi-asserted-by":"publisher","DOI":"10.1021\/ar200063v"},{"key":"S0031182013000450_ref33","doi-asserted-by":"publisher","DOI":"10.1038\/nature09099"},{"key":"S0031182013000450_ref108","doi-asserted-by":"publisher","DOI":"10.1007\/s12154-009-0032-8"},{"key":"S0031182013000450_ref31","doi-asserted-by":"publisher","DOI":"10.1016\/j.ab.2011.10.013"},{"key":"S0031182013000450_ref71","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e06-08-0736"},{"key":"S0031182013000450_ref30","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(00)81754-7"},{"key":"S0031182013000450_ref96","doi-asserted-by":"publisher","DOI":"10.1126\/science.1129720"},{"key":"S0031182013000450_ref26","doi-asserted-by":"publisher","DOI":"10.1038\/nature09107"},{"key":"S0031182013000450_ref46","doi-asserted-by":"crossref","first-page":"2996","DOI":"10.1016\/S0021-9258(17)42038-2","article-title":"Comparison of myristoyl-CoA:protein N-myristoyltransferases from three pathogenic fungi: Cryptococcus neoformans, Histoplasma capsulatum, and Candida albicans","volume":"269","author":"Lodge","year":"1994","journal-title":"Journal of Biological Chemistry"},{"key":"S0031182013000450_ref73","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2012.05.007"},{"key":"S0031182013000450_ref24","doi-asserted-by":"publisher","DOI":"10.1038\/nature08893"},{"key":"S0031182013000450_ref22","doi-asserted-by":"publisher","DOI":"10.1021\/bi0101401"},{"key":"S0031182013000450_ref8","doi-asserted-by":"publisher","DOI":"10.1002\/pmic.200300783"},{"key":"S0031182013000450_ref20","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808859"},{"key":"S0031182013000450_ref18","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1118370109"},{"key":"S0031182013000450_ref25","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2010.09.002"},{"key":"S0031182013000450_ref17","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.275.15.11017"},{"key":"S0031182013000450_ref44","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2008.11.015"},{"key":"S0031182013000450_ref107","first-page":"739","article-title":"Chemotherapeutically active nitro-compounds 0.4. 5-nitroimidazoles 0.3","volume":"28\u20131","author":"Winkelmann","year":"1978","journal-title":"Arzneimittel-Forschung\/Drug Research"},{"key":"S0031182013000450_ref43","doi-asserted-by":"publisher","DOI":"10.1007\/s00436-012-2886-x"},{"key":"S0031182013000450_ref45","doi-asserted-by":"publisher","DOI":"10.3390\/molecules15031378"},{"key":"S0031182013000450_ref47","doi-asserted-by":"publisher","DOI":"10.1001\/jama.1946.02870160015006"},{"key":"S0031182013000450_ref84","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2006.05.026"},{"key":"S0031182013000450_ref10","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20070692"},{"key":"S0031182013000450_ref85","doi-asserted-by":"publisher","DOI":"10.1126\/science.1193225"},{"key":"S0031182013000450_ref21","doi-asserted-by":"publisher","DOI":"10.1021\/bi0107997"},{"key":"S0031182013000450_ref66","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60484-X"},{"key":"S0031182013000450_ref39","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2006.01.009"},{"key":"S0031182013000450_ref48","doi-asserted-by":"publisher","DOI":"10.1126\/science.1185410"},{"key":"S0031182013000450_ref58","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)60034-8"},{"key":"S0031182013000450_ref110","doi-asserted-by":"publisher","DOI":"10.1021\/jm301160h"},{"key":"S0031182013000450_ref9","doi-asserted-by":"publisher","DOI":"10.1021\/cr200258w"},{"key":"S0031182013000450_ref36","doi-asserted-by":"publisher","DOI":"10.1039\/B917894E"},{"key":"S0031182013000450_ref101","doi-asserted-by":"publisher","DOI":"10.1038\/nature01510"},{"key":"S0031182013000450_ref106","unstructured":"WHO (2011). World Malaria Report 2011. World Health Organization, Geneva, Switzerland."},{"key":"S0031182013000450_ref78","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2006.04.008"},{"key":"S0031182013000450_ref86","doi-asserted-by":"crossref","first-page":"9732","DOI":"10.1016\/S0021-9258(18)92882-6","article-title":"Kinetic and structural evidence for a sequential ordered Bi Bi mechanism of catalysis by Saccharomyces cerevisiae myristoyl \u2013 CoA:protein N-myristoyltransferase","volume":"266","author":"Rudnick","year":"1991","journal-title":"Journal of Biological Chemistry"},{"key":"S0031182013000450_ref76","doi-asserted-by":"publisher","DOI":"10.1021\/jm301474t"},{"key":"S0031182013000450_ref15","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1120461109"},{"key":"S0031182013000450_ref83","doi-asserted-by":"publisher","DOI":"10.1021\/jm201095h"},{"key":"S0031182013000450_ref49","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jir842"},{"key":"S0031182013000450_ref29","doi-asserted-by":"publisher","DOI":"10.1093\/emboj\/18.8.2057"},{"key":"S0031182013000450_ref1","doi-asserted-by":"publisher","DOI":"10.1086\/324161"},{"key":"S0031182013000450_ref4","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2008.11.007"},{"key":"S0031182013000450_ref98","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.9.2708"},{"key":"S0031182013000450_ref90","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0001620"},{"key":"S0031182013000450_ref62","doi-asserted-by":"publisher","DOI":"10.1021\/jm030571c"},{"key":"S0031182013000450_ref38","doi-asserted-by":"publisher","DOI":"10.1016\/S1359-6446(04)03069-7"},{"key":"S0031182013000450_ref61","doi-asserted-by":"publisher","DOI":"10.1016\/j.protis.2009.05.003"},{"key":"S0031182013000450_ref70","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.01624"},{"key":"S0031182013000450_ref13","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0854.2012.01394.x"},{"key":"S0031182013000450_ref75","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111.292334"},{"key":"S0031182013000450_ref81","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2006.04.013"},{"key":"S0031182013000450_ref42","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.87"},{"key":"S0031182013000450_ref2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M509807200"},{"key":"S0031182013000450_ref5","doi-asserted-by":"publisher","DOI":"10.1038\/4202"},{"key":"S0031182013000450_ref91","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.05.014"},{"key":"S0031182013000450_ref92","doi-asserted-by":"publisher","DOI":"10.1128\/EC.1.2.241-248.2002"},{"key":"S0031182013000450_ref7","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307321200"},{"key":"S0031182013000450_ref97","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2010.09.006"},{"key":"S0031182013000450_ref11","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.200700301"},{"key":"S0031182013000450_ref12","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2009.12.032"},{"key":"S0031182013000450_ref99","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e04-06-0457"},{"key":"S0031182013000450_ref72","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2009.09.006"},{"key":"S0031182013000450_ref111","doi-asserted-by":"publisher","DOI":"10.1126\/science.290.5497.1761"},{"key":"S0031182013000450_ref64","doi-asserted-by":"publisher","DOI":"10.1038\/nature05572"},{"key":"S0031182013000450_ref59","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1242\/jcs.110.2.149","article-title":"Sequence and expression of Drosophila myristoyl-CoA: protein N-myristoyl transferase: evidence for proteolytic processing and membrane localisation","volume":"110","author":"Ntwasa","year":"1997","journal-title":"Journal of Cell Science"},{"key":"S0031182013000450_ref104","doi-asserted-by":"publisher","DOI":"10.1021\/cr078274t"},{"key":"S0031182013000450_ref3","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0001625"},{"key":"S0031182013000450_ref27","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-6851(02)00282-7"},{"key":"S0031182013000450_ref32","doi-asserted-by":"publisher","DOI":"10.1021\/jm300040p"},{"key":"S0031182013000450_ref34","doi-asserted-by":"publisher","DOI":"10.1042\/bj3480459"},{"key":"S0031182013000450_ref102","doi-asserted-by":"publisher","DOI":"10.1016\/j.parint.2006.12.005"},{"key":"S0031182013000450_ref19","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3117"},{"key":"S0031182013000450_ref23","doi-asserted-by":"publisher","DOI":"10.1038\/465297a"},{"key":"S0031182013000450_ref6","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(04)00449-0"},{"key":"S0031182013000450_ref51","doi-asserted-by":"publisher","DOI":"10.1016\/S0960-894X(01)00319-5"},{"key":"S0031182013000450_ref53","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2002.5425"}],"container-title":["Parasitology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0031182013000450","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T18:32:40Z","timestamp":1644863560000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0031182013000450\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4,24]]},"references-count":111,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2014,1]]}},"alternative-id":["S0031182013000450"],"URL":"https:\/\/doi.org\/10.1017\/s0031182013000450","relation":{},"ISSN":["0031-1820","1469-8161"],"issn-type":[{"value":"0031-1820","type":"print"},{"value":"1469-8161","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,4,24]]},"assertion":[{"value":"Copyright \u00a9 Cambridge University Press 2013\u00a0","name":"license","label":"License","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}}]}}