{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T23:04:13Z","timestamp":1788822253584,"version":"build-2803163510"},"reference-count":63,"publisher":"American Chemical Society (ACS)","issue":"5","license":[{"start":{"date-parts":[[2020,3,4]],"date-time":"2020-03-04T00:00:00Z","timestamp":1583280000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2020,3,4]],"date-time":"2020-03-04T00:00:00Z","timestamp":1583280000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2020,3,4]],"date-time":"2020-03-04T00:00:00Z","timestamp":1583280000000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"funder":[{"DOI":"10.13039\/501100002425","name":"Governo Brasil","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002425","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010665","name":"H2020 Marie Sklodowska-Curie Actions","doi-asserted-by":"publisher","award":["675555"],"award-info":[{"award-number":["675555"]}],"id":[{"id":"10.13039\/100010665","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001718","name":"Netherlands Organization for International Cooperation in Higher Education","doi-asserted-by":"publisher","award":["053\/14"],"award-info":[{"award-number":["053\/14"]}],"id":[{"id":"10.13039\/501100001718","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda??o de Amparo ? Pesquisa do Estado de S?o Paulo","doi-asserted-by":"publisher","award":["2013\/17577-9"],"award-info":[{"award-number":["2013\/17577-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda??o de Amparo ? Pesquisa do Estado de S?o Paulo","doi-asserted-by":"publisher","award":["2014\/23330-9"],"award-info":[{"award-number":["2014\/23330-9"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda??o de Amparo ? Pesquisa do Estado de S?o Paulo","doi-asserted-by":"publisher","award":["2015\/26722-8"],"award-info":[{"award-number":["2015\/26722-8"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda??o de Amparo ? Pesquisa do Estado de S?o Paulo","doi-asserted-by":"publisher","award":["2017\/03966-4"],"award-info":[{"award-number":["2017\/03966-4"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,5,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Malaria is a tropical disease that kills about half a million people around the world annually. Enzymatic reactions within pyrimidine biosynthesis have been proven to be essential for Plasmodium proliferation. Here we report on the essentiality of the second enzymatic step of the pyrimidine biosynthesis pathway, catalyzed by aspartate transcarbamoylase (ATC). Crystallization experiments using a double mutant ofPlasmodium falciparum ATC (PfATC) revealed the importance of the mutated residues for enzyme catalysis. Subsequently, this mutant was employed in protein interference assays (PIAs), which resulted in inhibition of parasite proliferation when parasites transfected with the double mutant were cultivated in medium lacking an excess of nutrients, including aspartate. Addition of 5 or 10 mg\/L of aspartate to the minimal medium restored the parasites\u2019 normal growth rate. In vitro and whole-cell assays in the presence of the compound Torin 2 showed inhibition of specific activity and parasite growth, respectively. In silico analyses revealed the potential binding mode of Torin 2 to PfATC. Furthermore, a transgenic ATC-overexpressing cell line exhibited a 10-fold increased tolerance to Torin 2 compared with control cultures. Taken together, our results confirm the antimalarial activity of Torin 2, suggesting PfATC as a target of this drug and a promising target for the development of novel antimalarials.<\/jats:p>","DOI":"10.1021\/acsinfecdis.9b00411","type":"journal-article","created":{"date-parts":[[2020,3,4]],"date-time":"2020-03-04T11:55:21Z","timestamp":1583322921000},"page":"986-999","source":"Crossref","is-referenced-by-count":17,"title":["Molecular Target Validation of Aspartate Transcarbamoylase\nfrom\n                    <i>Plasmodium falciparum<\/i>\n                    by Torin\n2"],"prefix":"10.1021","volume":"6","author":[{"given":"Soraya S.","family":"Bosch","sequence":"first","affiliation":[{"name":"University of Sa\u0303o Paulo , , Avenida Professor Lineu Prestes 1374 , - ,","place":["Sa\u0303o Paulo, SP, Brazil, 05508-000"]},{"name":"University of Groningen , , Antonius Deusinglaan 1 , ,","place":["Groningen, The Netherlands, 9700 AD"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergey","family":"Lunev","sequence":"additional","affiliation":[{"name":"University of Groningen , , Antonius Deusinglaan 1 , ,","place":["Groningen, The Netherlands, 9700 AD"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando A.","family":"Batista","sequence":"additional","affiliation":[{"name":"University of Groningen , , Antonius Deusinglaan 1 , ,","place":["Groningen, The Netherlands, 9700 AD"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marleen","family":"Linzke","sequence":"additional","affiliation":[{"name":"University of Sa\u0303o Paulo , , Avenida Professor Lineu Prestes 1374 , - ,","place":["Sa\u0303o Paulo, SP, Brazil, 05508-000"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6933-7590","authenticated-orcid":true,"given":"Thales","family":"Kronenberger","sequence":"additional","affiliation":[{"name":"University Hospital Tu\u0308bingen , , Otfried-Mu\u0308ller-Strasse 14 , ,","place":["Tu\u0308bingen, Germany, 72076"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9923-8873","authenticated-orcid":true,"given":"Alexander S. S.","family":"Do\u0308mling","sequence":"additional","affiliation":[{"name":"University of Groningen , , Antonius Deusinglaan 1 , ,","place":["Groningen, The Netherlands, 9700 AD"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9859-5177","authenticated-orcid":true,"given":"Matthew R.","family":"Groves","sequence":"additional","affiliation":[{"name":"University of Groningen , , Antonius Deusinglaan 1 , ,","place":["Groningen, The Netherlands, 9700 AD"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5987-1749","authenticated-orcid":true,"given":"Carsten","family":"Wrenger","sequence":"additional","affiliation":[{"name":"University of Sa\u0303o Paulo , , Avenida Professor Lineu Prestes 1374 , - ,","place":["Sa\u0303o Paulo, SP, Brazil, 05508-000"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,3,4]]},"reference":[{"key":"2026081806132088300_cit1","doi-asserted-by":"publisher","first-page":"31","DOI":"10.2174\/138945007779315524","article-title":"Targeting purine\nand pyrimidine metabolism in human apicomplexan parasites","volume":"8","author":"Hyde","year":"2007","journal-title":"Curr. Drug Targets"},{"key":"2026081806132088300_cit2","doi-asserted-by":"publisher","first-page":"987","DOI":"10.1016\/j.femsre.2005.03.004","article-title":"Purine\nand pyrimidine transport in pathogenic protozoa: from biology to therapy","volume":"29","author":"de Koning","year":"2005","journal-title":"FEMS Microbiol. Rev."},{"key":"2026081806132088300_cit3","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1016\/j.apjtm.2016.04.012","article-title":"Insights into the pyrimidine biosynthetic\npathway of human malaria parasite Plasmodium falciparum as chemotherapeutic\ntarget","volume":"9","author":"Krungkrai","year":"2016","journal-title":"Asian Pac. J. Trop. Med."},{"key":"2026081806132088300_cit4","doi-asserted-by":"crossref","first-page":"2103","DOI":"10.2174\/156802611796575948","article-title":"Purine and Pyrimidine Pathways as Targets in Plasmodium\nfalciparum","volume":"11","author":"Belen Cassera","year":"2011","journal-title":"Current Topics in Medicinal Chemistry"},{"key":"2026081806132088300_cit5","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1146\/annurev.micro.091208.073424","article-title":"Mitochondrial evolution\nand functions in malaria parasites","volume":"63","author":"Vaidya","year":"2009","journal-title":"Annu. Rev.\nMicrobiol."},{"key":"2026081806132088300_cit6","doi-asserted-by":"publisher","first-page":"929","DOI":"10.2174\/092986710790820660","article-title":"Inhibitors of the mitochondrial electron\ntransport chain and de novo pyrimidine biosynthesis as antimalarials:\nThe present status","volume":"17","author":"Rodrigues","year":"2010","journal-title":"Curr. Med. Chem."},{"key":"2026081806132088300_cit7","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/0166-6851(82)90035-4","article-title":"Enzymes of purine\nand pyrimidine metabolism from the human malaria parasite, Plasmodium\nfalciparum","volume":"5","author":"Reyes","year":"1982","journal-title":"Mol. Biochem. Parasitol."},{"key":"2026081806132088300_cit8","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1016\/j.molmed.2005.07.003","article-title":"Pyrimidine pathways\nin health and disease","volume":"11","author":"Loffler","year":"2005","journal-title":"Trends Mol. Med."},{"key":"2026081806132088300_cit9","doi-asserted-by":"crossref","DOI":"10.5772\/65659","article-title":"Identification and Validation of Novel Drug Targets\nfor the Treatment of Plasmodium falciparum Malaria: New Insights","volume-title":"Current Topics in Malaria","author":"Lunev","year":"2016"},{"key":"2026081806132088300_cit10","doi-asserted-by":"publisher","first-page":"41827","DOI":"10.1074\/jbc.M206854200","article-title":"Malarial dihydroorotate\ndehydrogenase. Substrate and inhibitor specificity","volume":"277","author":"Baldwin","year":"2002","journal-title":"J. Biol. Chem."},{"key":"2026081806132088300_cit11","doi-asserted-by":"publisher","first-page":"21847","DOI":"10.1074\/jbc.M501100200","article-title":"High-throughput screening for potent\nand selective inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase","volume":"280","author":"Baldwin","year":"2005","journal-title":"J. Biol. Chem."},{"key":"2026081806132088300_cit12","doi-asserted-by":"publisher","first-page":"296ra111","DOI":"10.1126\/scitranslmed.aaa6645","article-title":"A long-duration dihydroorotate dehydrogenase inhibitor\n(DSM265) for prevention and treatment of malaria","volume":"7","author":"Phillips","year":"2015","journal-title":"Sci. Transl. Med."},{"key":"2026081806132088300_cit13","volume-title":"Lehninger Principles of Biochemistry","author":"Nelson","year":"2013","edition":"6"},{"key":"2026081806132088300_cit14","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/S0021-9258(18)60389-8","article-title":"The enzymology\nof control by feedback inhibition","volume":"237","author":"Gerhart","year":"1962","journal-title":"J. Biol.\nChem."},{"key":"2026081806132088300_cit15","doi-asserted-by":"publisher","first-page":"7741","DOI":"10.1073\/pnas.1119683109","article-title":"Trapping and structure determination\nof an intermediate in the allosteric transition of aspartate transcarbamoylase","volume":"109","author":"Guo","year":"2012","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2026081806132088300_cit16","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1107\/S1744309113031114","article-title":"Expression, purification, crystallization and preliminary\nX-ray diffraction analysis of the aspartate transcarbamoylase domain\nof human CAD","volume":"69","author":"Ruiz-Ramos","year":"2013","journal-title":"Acta Crystallogr., Sect. F: Struct.\nBiol. Cryst. Commun."},{"key":"2026081806132088300_cit17","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1107\/S1744309109031959","article-title":"Crystallization and preliminary X-ray\nanalysis of aspartate transcarbamoylase from the parasitic protist\nTrypanosoma cruzi","volume":"65","author":"Matoba","year":"2009","journal-title":"Acta Crystallogr., Sect.\nF: Struct. Biol. Cryst. Commun."},{"key":"2026081806132088300_cit18","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1107\/S2053230X16008475","article-title":"Crystal structure of truncated aspartate transcarbamoylase\nfrom Plasmodium falciparum","volume":"72","author":"Lunev","year":"2016","journal-title":"Acta Crystallogr.,\nSect. F: Struct. Biol. Commun."},{"key":"2026081806132088300_cit19","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1016\/j.bbrc.2018.02.112","article-title":"Identification of a non-competitive\ninhibitor of Plasmodium falciparum aspartate transcarbamoylase","volume":"497","author":"Lunev","year":"2018","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"2026081806132088300_cit20","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1021\/ar200166p","article-title":"Structure\nand mechanisms of Escherichia coli aspartate transcarbamoylase","volume":"45","author":"Lipscomb","year":"2012","journal-title":"Acc. Chem. Res."},{"key":"2026081806132088300_cit21","doi-asserted-by":"publisher","first-page":"1069","DOI":"10.2174\/1389450117666160201115003","article-title":"Drug Target Validation Methods in\nMalaria - Protein Interference Assay (PIA) as a Tool for Highly Specific\nDrug Target Validation","volume":"18","author":"Meissner","year":"2017","journal-title":"Curr. Drug Targets"},{"key":"2026081806132088300_cit22","doi-asserted-by":"publisher","first-page":"e0195011","DOI":"10.1371\/journal.pone.0195011","article-title":"Oligomeric interfaces\nas a tool in drug discovery: Specific interference with activity of\nmalate dehydrogenase of Plasmodium falciparum in vitro","volume":"13","author":"Lunev","year":"2018","journal-title":"PLoS One"},{"key":"2026081806132088300_cit23","doi-asserted-by":"publisher","first-page":"5932","DOI":"10.1021\/jm0607294","article-title":"N-phosphonacetyl-l-isoasparagine a potent\nand specific inhibitor of Escherichia coli aspartate transcarbamoylase","volume":"49","author":"Eldo","year":"2006","journal-title":"J. Med. Chem."},{"key":"2026081806132088300_cit24","doi-asserted-by":"crossref","first-page":"6945","DOI":"10.1016\/S0021-9258(19)42149-2","article-title":"N-(Phosphonacetyl)-l-aspartate, a potent transition state analog inhibitor of aspartate\ntranscarbamylase, blocks proliferation of mammalian cells in culture","volume":"249","author":"Swyryd","year":"1974","journal-title":"J. Biol. Chem."},{"key":"2026081806132088300_cit25","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1016\/j.jmb.2011.05.036","article-title":"Crystallographic\nsnapshots of the complete catalytic cycle of the unregulated aspartate\ntranscarbamoylase from Bacillus subtilis","volume":"411","author":"Harris","year":"2011","journal-title":"J.\nMol. Biol."},{"key":"2026081806132088300_cit26","doi-asserted-by":"publisher","first-page":"6415","DOI":"10.1021\/bi030213b","article-title":"Aspartate transcarbamylase (ATCase) of Escherichia\ncoli: a new crystalline R-state bound to PALA, or to product analogues\ncitrate and phosphate","volume":"43","author":"Huang","year":"2004","journal-title":"Biochemistry"},{"key":"2026081806132088300_cit27","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1016\/S0022-2836(02)01228-7","article-title":"Aspartate transcarbamylase from the hyperthermophilic archaeon Pyrococcus\nabyssi: Thermostability and 1.8 \u00c5 resolution crystal structure\nof the catalytic subunit complexed with the bisubstrate analogue N-phosphonacetyl-l-aspartate","volume":"326","author":"Van Boxstael","year":"2003","journal-title":"J. Mol. Biol."},{"key":"2026081806132088300_cit28","doi-asserted-by":"publisher","first-page":"1081","DOI":"10.1016\/j.str.2016.05.001","article-title":"Structure and Functional Characterization\nof Human Aspartate Transcarbamoylase, the Target of the Anti-tumoral\nDrug PALA","volume":"24","author":"Ruiz-Ramos","year":"2016","journal-title":"Structure"},{"key":"2026081806132088300_cit29","first-page":"3080","article-title":"Selective\ninhibition of pyrimidine biosynthesis and effect on proliferative\ngrowth of colonic cancer cells","volume":"37","author":"Tsuboi","year":"1977","journal-title":"Cancer Res."},{"key":"2026081806132088300_cit30","first-page":"4441","article-title":"Biochemistry and clinical activity of N-(phosphonacetyl)-l-aspartate: a review","volume":"48","author":"Grem","year":"1988","journal-title":"Cancer Res."},{"key":"2026081806132088300_cit31","doi-asserted-by":"publisher","first-page":"E2838","DOI":"10.1073\/pnas.1306097110","article-title":"Torins\nare potent antimalarials that block replenishment of Plasmodium liver\nstage parasitophorous vacuole membrane proteins","volume":"110","author":"Hanson","year":"2013","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2026081806132088300_cit32","doi-asserted-by":"publisher","first-page":"3743","DOI":"10.1038\/srep03743","article-title":"Chemical signatures\nand new drug targets for gametocytocidal drug development","volume":"4","author":"Sun","year":"2015","journal-title":"Sci. Rep."},{"key":"2026081806132088300_cit33","doi-asserted-by":"publisher","first-page":"408","DOI":"10.1016\/S0003-2697(69)80008-4","article-title":"Modified methods\nfor the determination of carbamyl aspartate","volume":"32","author":"Prescott","year":"1969","journal-title":"Anal. Biochem."},{"key":"2026081806132088300_cit34","doi-asserted-by":"publisher","first-page":"8881","DOI":"10.1073\/pnas.0503742102","article-title":"Structural\nbasis for ordered substrate binding and cooperativity in aspartate\ntranscarbamoylase","volume":"102","author":"Wang","year":"2005","journal-title":"Proc. Natl. Acad. Sci. U.\nS. A."},{"key":"2026081806132088300_cit35","doi-asserted-by":"publisher","first-page":"e00779","DOI":"10.1002\/mbo3.779","article-title":"Oligomeric Protein\nInterference Validates Druggability of Aspartate Interconversion in\nPlasmodium falciparum","volume":"28","author":"Batista","year":"2019","journal-title":"MicrobiologyOpen"},{"key":"2026081806132088300_cit36","doi-asserted-by":"publisher","first-page":"1710","DOI":"10.1172\/JCI103763","article-title":"The Levels of Individual Free Amino\nAcids in the Plasma of Normal Man at Various Intervals After a High-Protein\nMeal1","volume":"37","author":"Frame","year":"1958","journal-title":"J. Clin. Invest."},{"key":"2026081806132088300_cit37","doi-asserted-by":"publisher","first-page":"733","DOI":"10.1093\/ajcn\/27.7.733","article-title":"Serum proteins\nand plasma free amino acids in severe malnutrition","volume":"27","author":"Baertl","year":"1974","journal-title":"Am. J. Clin. Nutr."},{"key":"2026081806132088300_cit38","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1093\/ajcn\/14.6.320","article-title":"Serum Amino Acids In Kwashiorkor. Ii. An Abbreviated\nMethod Of Estimation And Its Application","volume":"14","author":"Whitehead","year":"1964","journal-title":"Am.\nJ. Clin. Nutr."},{"key":"2026081806132088300_cit39","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1093\/ndt\/17.3.413","article-title":"Free amino\nacids in plasma, red blood cells, polymorphonuclear leukocytes, and\nmuscle in normal and uraemic children","volume":"17","author":"Canepa","year":"2002","journal-title":"Nephrol.,\nDial., Transplant."},{"key":"2026081806132088300_cit40","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/S0021-9258(18)71179-4","article-title":"The free amino acids of human blood plasma","volume":"211","author":"Stein","year":"1954","journal-title":"J. Biol. Chem."},{"issue":"1","key":"2026081806132088300_cit41","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1093\/jn\/40.1.145","article-title":"Amino acids in the blood and urine\nof human subjects ingesting different amounts of the same proteins","volume":"40","author":"Steele","year":"1950","journal-title":"J. Nutr."},{"key":"2026081806132088300_cit42","doi-asserted-by":"publisher","first-page":"e16957","DOI":"10.1371\/journal.pone.0016957","article-title":"The human serum metabolome","volume":"6","author":"Psychogios","year":"2011","journal-title":"PLoS\nOne"},{"key":"2026081806132088300_cit43","doi-asserted-by":"publisher","first-page":"8840","DOI":"10.1073\/pnas.0601876103","article-title":"Plasmodium falciparum ensures its\namino acid supply with multiple acquisition pathways and redundant\nproteolytic enzyme systems","volume":"103","author":"Liu","year":"2006","journal-title":"Proc. Natl. Acad.\nSci. U. S. A."},{"key":"2026081806132088300_cit44","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1016\/S0009-9236(01)62844-3","article-title":"Fluvoxamine-theophylline interaction:\ngap between in vitro and in vivo inhibition constants toward cytochrome\nP4501A2","volume":"70","author":"Yao","year":"2001","journal-title":"Clin. Pharmacol. Ther."},{"key":"2026081806132088300_cit45","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1124\/dmd.31.5.565","article-title":"Comparison of in vitro and in vivo\ninhibition potencies of fluvoxamine toward CYP2C19","volume":"31","author":"Yao","year":"2003","journal-title":"Drug Metab. Dispos."},{"key":"2026081806132088300_cit46","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.aquatox.2003.09.004","article-title":"Comparative study on the in vitro\/in\nvivo estrogenic potencies of 17beta-estradiol, estrone, 17alpha-ethynylestradiol\nand nonylphenol","volume":"66","author":"Van\nden Belt","year":"2004","journal-title":"Aquat. Toxicol."},{"key":"2026081806132088300_cit47","doi-asserted-by":"publisher","first-page":"3743","DOI":"10.1038\/srep03743","article-title":"Chemical signatures\nand new drug targets for gametocytocidal drug development","volume":"4","author":"Sun","year":"2015","journal-title":"Sci. Rep."},{"key":"2026081806132088300_cit48","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1126\/science.781840","article-title":"Human malaria parasites\nin continuous culture","volume":"193","author":"Trager","year":"1976","journal-title":"Science"},{"key":"2026081806132088300_cit49","doi-asserted-by":"publisher","first-page":"677","DOI":"10.1111\/j.1462-5822.2010.01426.x","article-title":"Secretion of an acid\nphosphatase provides a possible mechanism to acquire host nutrients\nby Plasmodium falciparum","volume":"12","author":"Muller","year":"2010","journal-title":"Cell. Microbiol."},{"key":"2026081806132088300_cit50","doi-asserted-by":"publisher","first-page":"973","DOI":"10.1073\/pnas.92.4.973","article-title":"Transfection of Plasmodium falciparum\nwithin human red blood cells","volume":"92","author":"Wu","year":"1995","journal-title":"Proc. Natl. Acad.\nSci. U. S. A."},{"key":"2026081806132088300_cit51","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1016\/j.pt.2009.10.006","article-title":"Vitamin B metabolism in Plasmodium\nfalciparum as a source of drug targets","volume":"26","author":"Muller","year":"2010","journal-title":"Trends\nParasitol."},{"key":"2026081806132088300_cit52","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.1515\/BC.2006.197","article-title":"The human\nmalaria parasite Plasmodium falciparum expresses an atypical N-terminally\nextended pyrophosphokinase with specificity for thiamine","volume":"387","author":"Eschbach","year":"2006","journal-title":"Biol. Chem."},{"key":"2026081806132088300_cit53","doi-asserted-by":"publisher","first-page":"8840","DOI":"10.1073\/pnas.0601876103","article-title":"Plasmodium\nfalciparum ensures its amino acid supply with multiple acquisition\npathways and redundant proteolytic enzyme systems","volume":"103","author":"Liu","year":"2006","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"2026081806132088300_cit54","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1128\/AAC.48.5.1803-1806.2004","article-title":"Simple and inexpensive\nfluorescence-based technique for high-throughput antimalarial drug\nscreening","volume":"48","author":"Smilkstein","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"2026081806132088300_cit55","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1107\/S0021889812011715","article-title":"XDSAPP: A graphical user interface for the convenient\nprocessing of diffraction data using XDS. Vol. 45","volume":"45","author":"Krug","year":"2012","journal-title":"J. Appl. Crystallogr."},{"key":"2026081806132088300_cit56","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1107\/S0907444910045749","article-title":"Overview\nof the CCP4 suite and current developments","volume":"67","author":"Winn","year":"2011","journal-title":"Acta Crystallogr., Sect. D: Biol. Crystallogr."},{"key":"2026081806132088300_cit57","doi-asserted-by":"publisher","first-page":"486","DOI":"10.1107\/S0907444910007493","article-title":"Features and development of Coot","volume":"66","author":"Emsley","year":"2010","journal-title":"Acta Crystallogr., Sect. D: Biol. Crystallogr."},{"key":"2026081806132088300_cit58","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1107\/S0907444996012255","article-title":"Refinement\nof macromolecular structures by the maximum-likelihood method","volume":"53","author":"Murshudov","year":"1997","journal-title":"Acta Crystallogr., Sect. D: Biol. Crystallogr."},{"key":"2026081806132088300_cit59","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1093\/nar\/28.1.235","article-title":"The Protein Data Bank","volume":"28","author":"Berman","year":"2000","journal-title":"Nucleic acids research"},{"key":"2026081806132088300_cit60","doi-asserted-by":"publisher","first-page":"534","DOI":"10.1021\/jm050540c","article-title":"Novel Procedure for\nModeling Ligand\/Receptor Induced Fit Effects","volume":"49","author":"Sherman","year":"2006","journal-title":"J. Med. Chem."},{"key":"2026081806132088300_cit61","unstructured":"Proceedings of the 2006 ACM\/IEEE Conference\non Supercomputing."},{"key":"2026081806132088300_cit62","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1021\/acs.jctc.5b00864","article-title":"OPLS3:\nA Force Field Providing Broad Coverage of Drug-like Small Molecules\nand Proteins","volume":"12","author":"Harder","year":"2016","journal-title":"J. Chem. Theory Comput."},{"key":"2026081806132088300_cit63","doi-asserted-by":"publisher","first-page":"444","DOI":"10.1093\/bioinformatics\/btw638","article-title":"PyMod 2.0: improvements in protein sequence-structure\nanalysis and homology modeling within PyMOL","volume":"33","author":"Janson","year":"2016","journal-title":"Bioinformatics"}],"container-title":["ACS Infectious Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acsinfecdis.9b00411","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/aidcbc\/article-pdf\/6\/5\/986\/12727053\/id9b00411.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/aidcbc\/article-pdf\/6\/5\/986\/12727053\/id9b00411.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T10:23:56Z","timestamp":1787048636000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/aidcbc\/article\/6\/5\/986\/1292813\/Molecular-Target-Validation-of-Aspartate"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,3,4]]},"references-count":63,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2020,3,4]]},"published-print":{"date-parts":[[2020,5,8]]}},"URL":"https:\/\/doi.org\/10.1021\/acsinfecdis.9b00411","relation":{},"ISSN":["2373-8227"],"issn-type":[{"value":"2373-8227","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,3,4]]}}}