{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T07:22:51Z","timestamp":1785396171926,"version":"3.56.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1010887","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T00:00:00Z","timestamp":1666569600000}}],"reference-count":96,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T00:00:00Z","timestamp":1665532800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI076276"],"award-info":[{"award-number":["R01AI076276"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["R01AI125565"],"award-info":[{"award-number":["R01AI125565"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Center for Quantitative Biology","award":["P50 GM071508"],"award-info":[{"award-number":["P50 GM071508"]}]},{"name":"NIH","award":["5T32GM125592-01"],"award-info":[{"award-number":["5T32GM125592-01"]}]},{"name":"Sir Keith Murdoch Fellowship"},{"DOI":"10.13039\/100000968","name":"American Heart Association","doi-asserted-by":"publisher","award":["16POST26420067"],"award-info":[{"award-number":["16POST26420067"]}],"id":[{"id":"10.13039\/100000968","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p><jats:italic>Plasmodium<\/jats:italic>parasites are reliant on the Apicomplexan AP2 (ApiAP2) transcription factor family to regulate gene expression programs. AP2 DNA binding domains have no homologs in the human or mosquito host genomes, making them potential antimalarial drug targets. Using an<jats:italic>in-silico<\/jats:italic>screen to dock thousands of small molecules into the crystal structure of the AP2-EXP (Pf3D7_1466400) AP2 domain (PDB:3IGM), we identified putative AP2-EXP interacting compounds. Four compounds were found to block DNA binding by AP2-EXP and at least one additional ApiAP2 protein. Our top ApiAP2 competitor compound perturbs the transcriptome of<jats:italic>P<\/jats:italic>.<jats:italic>falciparum<\/jats:italic>trophozoites and results in a decrease in abundance of log<jats:sub>2<\/jats:sub>fold change &gt; 2 for 50% (46\/93) of AP2-EXP target genes. Additionally, two ApiAP2 competitor compounds have multi-stage anti-<jats:italic>Plasmodium<\/jats:italic>activity against blood and mosquito stage parasites. In summary, we describe a novel set of antimalarial compounds that interact with AP2 DNA binding domains. These compounds may be used for future chemical genetic interrogation of ApiAP2 proteins or serve as starting points for a new class of antimalarial therapeutics.<\/jats:p>","DOI":"10.1371\/journal.ppat.1010887","type":"journal-article","created":{"date-parts":[[2022,10,12]],"date-time":"2022-10-12T17:40:56Z","timestamp":1665596456000},"page":"e1010887","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":30,"title":["Inhibitors of ApiAP2 protein DNA binding exhibit multistage activity against Plasmodium parasites"],"prefix":"10.1371","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6651-6366","authenticated-orcid":true,"given":"Timothy James","family":"Russell","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erandi K.","family":"De Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valerie M.","family":"Crowley","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathryn","family":"Shaw-Saliba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Namita","family":"Dube","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle","family":"Josling","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charisse Flerida A.","family":"Pasaje","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Kouskoumvekaki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gianni","family":"Panagiotou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacquin C.","family":"Niles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"Jacobs-Lorena","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Denise Okafor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco-Javier","family":"Gamo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6173-5882","authenticated-orcid":true,"given":"Manuel","family":"Llin\u00e1s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2022,10,12]]},"reference":[{"key":"ppat.1010887.ref001","unstructured":"WHO. Word Malaria Report 2021. Word Malaria report Geneva: World Health Organization. (2021). Licence: CC. 2021. 2013\u20132015 p."},{"issue":"2","key":"ppat.1010887.ref002","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1007\/s40471-021-00266-5","article-title":"Antimalarial Drug Resistance and Implications for the WHO Global Technical Strategy.","volume":"8","author":"MM Ippolito","year":"2021","journal-title":"Curr Epidemiol Reports"},{"issue":"3","key":"ppat.1010887.ref003","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1016\/j.cell.2016.07.055","article-title":"Malaria: Biology and Disease.","volume":"167","author":"AF Cowman","year":"2016","journal-title":"Cell"},{"issue":"11","key":"ppat.1010887.ref004","doi-asserted-by":"crossref","first-page":"2951","DOI":"10.1016\/j.celrep.2018.02.075","article-title":"A Specific PfEMP1 Is Expressed in P. falciparum Sporozoites and Plays a Role in Hepatocyte Infection","volume":"22","author":"G Zangh\u00ec","year":"2018","journal-title":"Cell Rep"},{"issue":"1","key":"ppat.1010887.ref005","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1371\/journal.pbio.0000005","article-title":"The transcriptome of the intraerythrocytic developmental cycle of Plasmodium falciparum","volume":"1","author":"Z Bozdech","year":"2003","journal-title":"PLoS Biol"},{"issue":"13","key":"ppat.1010887.ref006","doi-asserted-by":"crossref","first-page":"7825","DOI":"10.1093\/nar\/gkx464","article-title":"Nascent RNA sequencing reveals mechanisms of gene regulation in the human malaria parasite Plasmodium falciparum","volume":"45","author":"XM Lu","year":"2017","journal-title":"Nucleic Acids Res"},{"key":"ppat.1010887.ref007","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1101\/gr.217356.116","article-title":"Capturing in vivo RNA transcriptional dynamics from the malaria parasite Plasmodium falciparum","volume":"27","author":"HJ Painter","year":"2017","journal-title":"Genome Res"},{"issue":"5639","key":"ppat.1010887.ref008","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1126\/science.1087025","article-title":"Discovery of gene function by expression profiling of the malaria parasite life cycle","volume":"301","author":"KG Le Roch","year":"2003","journal-title":"Science"},{"issue":"8","key":"ppat.1010887.ref009","first-page":"1","article-title":"Quantitative time-course profiling of parasite and host cell proteins in the human malaria parasite Plasmodium falciparum","volume":"10","author":"BJ Foth","year":"2011","journal-title":"Mol Cell Proteomics"},{"issue":"December","key":"ppat.1010887.ref010","first-page":"1","article-title":"From Genes to Transcripts, a Tightly Regulated Journey in Plasmodium.","volume":"10","author":"T Hollin","year":"2020","journal-title":"Front Cell Infect Microbiol"},{"issue":"1","key":"ppat.1010887.ref011","first-page":"1","article-title":"The Apicomplexan AP2 family: Integral factors regulating","volume":"176","author":"HJ Painter","year":"2012","journal-title":"Plasmodium development"},{"issue":"10","key":"ppat.1010887.ref012","doi-asserted-by":"crossref","first-page":"e1001165","DOI":"10.1371\/journal.ppat.1001165","article-title":"Identification and Genome-Wide Prediction of DNA Binding Specificities for the ApiAP2 family of regulators from the malaria parasite.","volume":"6","author":"TL Campbell","year":"2010","journal-title":"PLoS Pathog"},{"issue":"13","key":"ppat.1010887.ref013","doi-asserted-by":"crossref","first-page":"3994","DOI":"10.1093\/nar\/gki709","article-title":"Discovery of the principal specific transcription factors of Apicomplexa and their implication for the evolution of the AP2-integrase DNA binding domains","volume":"33","author":"S Balaji","year":"2005","journal-title":"Nucleic Acids Res"},{"issue":"2","key":"ppat.1010887.ref014","doi-asserted-by":"crossref","DOI":"10.3390\/pathogens8020047","article-title":"ApiAP2 Transcription Factors in Apicomplexan Parasites.","volume":"8","author":"M Jeninga","year":"2019","journal-title":"Pathogens"},{"issue":"6388","key":"ppat.1010887.ref015","doi-asserted-by":"crossref","first-page":"eaap7847","DOI":"10.1126\/science.aap7847","article-title":"Uncovering the essential genes of the human malaria parasite Plasmodium falciparum by saturation mutagenesis","volume":"360","author":"M Zhang","year":"2018","journal-title":"Science"},{"issue":"16","key":"ppat.1010887.ref016","doi-asserted-by":"crossref","first-page":"9264","DOI":"10.1093\/nar\/gkab683","article-title":"A cascade of transcriptional repression determines sexual commitment and development in Plasmodium falciparum.","volume":"49","author":"X Shang","year":"2021","journal-title":"Nucleic Acids Res"},{"issue":"6","key":"ppat.1010887.ref017","doi-asserted-by":"crossref","first-page":"3413","DOI":"10.1093\/nar\/gkac176","article-title":"Genome-wide landscape of ApiAP2 transcription factors reveals a heterochromatin-associated regulatory network during Plasmodium falciparum blood-stage development.","volume":"50","author":"X Shang","year":"2022","journal-title":"Nucleic Acids Res"},{"issue":"6","key":"ppat.1010887.ref018","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.chom.2017.05.006","article-title":"Red Blood Cell Invasion by the Malaria Parasite Is Coordinated by the PfAP2-I Transcription Factor.","volume":"21","author":"JM Santos","year":"2017","journal-title":"Cell Host Microbe"},{"issue":"1","key":"ppat.1010887.ref019","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1038\/s41467-020-15026-0","article-title":"Dissecting the role of PfAP2-G in malaria gametocytogenesis","volume":"11","author":"GA Josling","year":"2020","journal-title":"Nat Commun"},{"issue":"2","key":"ppat.1010887.ref020","doi-asserted-by":"crossref","first-page":"e1000784","DOI":"10.1371\/journal.ppat.1000784","article-title":"A major role for the Plasmodium falciparum ApiAP2 protein PfSIP2 in chromosome end biology.","volume":"6","author":"C Flueck","year":"2010","journal-title":"PLoS Pathog"},{"issue":"1","key":"ppat.1010887.ref021","first-page":"14042","article-title":"An ApiAP2 member regulates expression of clonally variant genes of the human malaria parasite Plasmodium falciparum. Sci Rep","volume":"7","author":"RM Martins","year":"2017"},{"issue":"5","key":"ppat.1010887.ref022","doi-asserted-by":"crossref","first-page":"102444","DOI":"10.1016\/j.isci.2021.102444","article-title":"The ApiAP2 factor PfAP2-HC is an integral component of heterochromatin in the malaria parasite Plasmodium falciparum.","volume":"24","author":"E Carrington","year":"2021","journal-title":"iScience"},{"issue":"March","key":"ppat.1010887.ref023","doi-asserted-by":"crossref","first-page":"e12742","DOI":"10.1111\/cmi.12742","article-title":"PfAP2Tel, harbouring a non-canonical DNA-binding AP2 domain, binds to Plasmodium falciparum telomeres","volume":"19","author":"M Sierra-Miranda","year":"2017","journal-title":"Cell Microbiol"},{"issue":"1","key":"ppat.1010887.ref024","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.chom.2016.12.003","article-title":"A Knockout Screen of ApiAP2 Genes Reveals Networks of Interacting Transcriptional Regulators Controlling the Plasmodium Life Cycle.","volume":"21","author":"K Modrzynska","year":"2017","journal-title":"Cell Host Microbe"},{"issue":"5","key":"ppat.1010887.ref025","doi-asserted-by":"crossref","first-page":"1005","DOI":"10.1111\/mmi.14676","article-title":"The PfAP2-G2 transcription factor is a critical regulator of gametocyte maturation","volume":"115","author":"S Singh","year":"2021","journal-title":"Mol Microbiol"},{"issue":"6","key":"ppat.1010887.ref026","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1128\/mBio.01986-17","article-title":"Systematic CRISPR-Cas9-Mediated ApiAP2 Genes Reveal Functional Insights into Parasite Development.","volume":"8","author":"C Zhang","year":"2017","journal-title":"MBio"},{"key":"ppat.1010887.ref027","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1038\/nature12970","article-title":"A cascade of DNA binding proteins for sexual commitment and development in Plasmodium.","volume":"507","author":"A Sinha","year":"2014","journal-title":"Nature"},{"issue":"7491","key":"ppat.1010887.ref028","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1038\/nature12920","article-title":"A transcriptional switch underlies commitment to sexual development in malaria parasites.","volume":"507","author":"BFC Kafsack","year":"2014","journal-title":"Nature"},{"issue":"11","key":"ppat.1010887.ref029","doi-asserted-by":"crossref","first-page":"e47557","DOI":"10.1371\/journal.pone.0047557","article-title":"Identification of an AP2-family Protein That Is Critical for Malaria Liver Stage Development.","volume":"7","author":"S Iwanaga","year":"2012","journal-title":"PLoS One"},{"issue":"4","key":"ppat.1010887.ref030","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1111\/j.1365-2958.2009.07005.x","article-title":"Transcription factor AP2-Sp and its target genes in malarial sporozoites.","volume":"75","author":"M Yuda","year":"2010","journal-title":"Mol Microbiol"},{"issue":"6","key":"ppat.1010887.ref031","doi-asserted-by":"crossref","first-page":"1402","DOI":"10.1111\/j.1365-2958.2009.06609.x","article-title":"Identification of a transcription factor in the mosquito-invasive stage of malaria parasites","volume":"71","author":"M Yuda","year":"2009","journal-title":"Mol Microbiol"},{"issue":"1","key":"ppat.1010887.ref032","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1111\/mmi.14334","article-title":"Female-specific gene regulation in malaria parasites by an AP2-family transcription factor","volume":"113","author":"M Yuda","year":"2020","journal-title":"Mol Microbiol"},{"issue":"5","key":"ppat.1010887.ref033","doi-asserted-by":"crossref","first-page":"e51660","DOI":"10.15252\/embr.202051660","article-title":"Plasmodium transcription repressor AP2-O3 regulates sex-specific identity of gene expression in female gametocytes","volume":"22","author":"Z Li","year":"2021","journal-title":"EMBO Rep"},{"key":"ppat.1010887.ref034","doi-asserted-by":"crossref","first-page":"631444","DOI":"10.3389\/fmicb.2020.631444","article-title":"PfAP2-G2 Is Associated to Production and Maturation of Gametocytes in Plasmodium falciparum via Regulating the Expression of PfMDV-1.","volume":"11","author":"Y Xu","year":"2021","journal-title":"Front Microbiol"},{"issue":"9","key":"ppat.1010887.ref035","doi-asserted-by":"crossref","first-page":"1163","DOI":"10.1038\/s41564-021-00940-w","article-title":"A heat-shock response regulated by the PfAP2-HS transcription factor protects human malaria parasites from febrile temperatures.","volume":"6","author":"E Tint\u00f3-Font","year":"2021","journal-title":"Nat Microbiol"},{"issue":"11","key":"ppat.1010887.ref036","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1038\/s41568-019-0196-7","article-title":"Targeting transcription factors in cancer\u2014from undruggable to reality.","volume":"19","author":"JH Bushweller","year":"2019","journal-title":"Nat Rev Cancer"},{"key":"ppat.1010887.ref037","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.pharmthera.2017.12.012","article-title":"Selective estrogen receptor modulators (SERMs) and selective estrogen receptor degraders (SERDs) in cancer treatment.","volume":"186","author":"HK Patel","year":"2018","journal-title":"Pharmacol Ther"},{"issue":"7","key":"ppat.1010887.ref038","doi-asserted-by":"crossref","first-page":"2815","DOI":"10.1172\/JCI91788","article-title":"Genetic regulation of the RUNX transcription factor family has antitumor effects","volume":"127","author":"K Morita","year":"2017","journal-title":"J Clin Invest"},{"issue":"6","key":"ppat.1010887.ref039","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1038\/onc.2015.215","article-title":"Small-molecule inhibitors targeting the DNA-binding domain of STAT3 suppress tumor growth, metastasis and STAT3 target gene expression in vivo","volume":"35","author":"W Huang","year":"2016","journal-title":"Oncogene"},{"issue":"3","key":"ppat.1010887.ref040","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.jmb.2009.11.004","article-title":"Structural Determinants of DNA Binding by a P. falciparum ApiAP2 Transcriptional Regulator.","volume":"395","author":"SE Lindner","year":"2010","journal-title":"J Mol Biol"},{"issue":"14","key":"ppat.1010887.ref041","doi-asserted-by":"crossref","first-page":"1639","DOI":"10.1002\/(SICI)1096-987X(19981115)19:14<1639::AID-JCC10>3.0.CO;2-B","article-title":"Automated docking using a Lamarckian genetic algorithm and an empirical binding free energy function","volume":"19","author":"GM Morris","year":"1998","journal-title":"J Comput Chem"},{"issue":"7296","key":"ppat.1010887.ref042","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1038\/nature09107","article-title":"Thousands of chemical starting points for antimalarial lead identification","volume":"465","author":"FJ Gamo","year":"2010","journal-title":"Nature"},{"issue":"D1","key":"ppat.1010887.ref043","doi-asserted-by":"crossref","first-page":"D1074","DOI":"10.1093\/nar\/gkx1037","article-title":"DrugBank 5.0: A major update to the DrugBank database for 2018","volume":"46","author":"DS Wishart","year":"2018","journal-title":"Nucleic Acids Res"},{"issue":"18","key":"ppat.1010887.ref044","doi-asserted-by":"crossref","first-page":"5484","DOI":"10.1093\/emboj\/17.18.5484","article-title":"A novel mode of DNA recognition by a \u03b2-sheet revealed by the solution structure of the GCC-box binding domain in complex with DNA","volume":"17","author":"MD Allen","year":"1998","journal-title":"EMBO J"},{"issue":"2","key":"ppat.1010887.ref045","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1242\/dev.122.2.509","article-title":"A comparison of the properties of Sox-3 with Sry and two related genes, Sox-1 and Sox-2","volume":"122","author":"J Collignon","year":"1996","journal-title":"Development"},{"issue":"17","key":"ppat.1010887.ref046","doi-asserted-by":"crossref","first-page":"5415","DOI":"10.1021\/bi015977a","article-title":"Solution structure of the first HMG box domain in human upstream binding factor","volume":"41","author":"Y Xu","year":"2002","journal-title":"Biochemistry"},{"issue":"10","key":"ppat.1010887.ref047","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/j.tibtech.2007.08.003","article-title":"Harnessing DNA intercalation.","volume":"25","author":"\u00d6 Persil","year":"2007","journal-title":"Trends Biotechnol"},{"key":"ppat.1010887.ref048","doi-asserted-by":"crossref","first-page":"S218","DOI":"10.1016\/j.matpr.2017.09.190","article-title":"Binding Mechanism of Fluorescent Dyes to DNA Characterized by Magnetic Tweezers","volume":"4","author":"Y Wang","year":"2017","journal-title":"Mater Today Proc"},{"issue":"4","key":"ppat.1010887.ref049","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1038\/nmeth.4223","article-title":"A genetic system to study Plasmodium falciparum protein function.","volume":"14","author":"J Birnbaum","year":"2017","journal-title":"Nat Methods"},{"key":"ppat.1010887.ref050","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1186\/1475-2875-11-187","article-title":"New Agilent platform DNA microarrays for transcriptome analysis of Plasmodium falciparum and Plasmodium berghei for the malaria research community","volume":"11","author":"BFC Kafsack","year":"2012","journal-title":"Malar J"},{"issue":"4","key":"ppat.1010887.ref051","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1093\/nar\/gkj517","article-title":"Comparative whole genome transcriptome analysis of three Plasmodium falciparum strains","volume":"34","author":"M Llin\u00e1s","year":"2006","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"ppat.1010887.ref052","doi-asserted-by":"crossref","DOI":"10.2202\/1544-6115.1027","article-title":"Linear models and empirical Bayes methods for assessing differential expression in microarray experiments.","volume":"3","author":"GK Smyth","year":"2011","journal-title":"Stat Appl Genet Mol Biol"},{"issue":"1","key":"ppat.1010887.ref053","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1093\/nar\/gkg081","article-title":"PlasmoDB: The Plasmodium genome resource. A database integrating experimental and computational data","volume":"31","author":"A Bahl","year":"2003","journal-title":"Nucleic Acids Res"},{"key":"ppat.1010887.ref054","author":"DP Sangurdekar","year":"2014","journal-title":"The Rnits package for normalization and inference of differential expression in time series microarray data"},{"key":"ppat.1010887.ref055","article-title":"Targetome analysis of malaria sporozoite transcription factor AP2-Sp reveals its role as a master regulator.","author":"M Yuda","year":"2022","journal-title":"bioRxiv"},{"issue":"5","key":"ppat.1010887.ref056","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1093\/nar\/gkv1214","article-title":"The nucleosome landscape of Plasmodium falciparum reveals chromatin architecture and dynamics of regulatory sequences","volume":"44","author":"PR Kensche","year":"2015","journal-title":"Nucleic Acids Res"},{"issue":"12","key":"ppat.1010887.ref057","doi-asserted-by":"crossref","first-page":"e1001223","DOI":"10.1371\/journal.ppat.1001223","article-title":"H2A.Z demarcates intergenic regions of the Plasmodium falciparum epigenome that are dynamically marked by H3K9ac and H3K4me3.","volume":"6","author":"R B\u00e1rtfai","year":"2010","journal-title":"PLoS Pathog"},{"issue":"6","key":"ppat.1010887.ref058","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1016\/j.chom.2015.05.009","article-title":"A Plasmodium Falciparum Bromodomain Protein Regulates Invasion Gene Expression.","volume":"17","author":"GA Josling","year":"2015","journal-title":"Cell Host Microbe"},{"issue":"1","key":"ppat.1010887.ref059","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1186\/s12864-020-06787-5","article-title":"Refining the transcriptome of the human malaria parasite Plasmodium falciparum using amplification-free RNA-seq","volume":"21","author":"L Chappell","year":"2020","journal-title":"BMC Genomics"},{"issue":"4","key":"ppat.1010887.ref060","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.chom.2018.03.007","article-title":"Chromatin Accessibility-Based Characterization of the Gene Regulatory Network Underlying Plasmodium falciparum Blood-Stage Development.","volume":"23","author":"CG Toenhake","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ppat.1010887.ref061","doi-asserted-by":"crossref","first-page":"10727","DOI":"10.1038\/ncomms10727","article-title":"Synthetic RNA-protein modules integrated with native translation mechanisms to control gene expression in malaria parasites","volume":"7","author":"SM Ganesan","year":"2016","journal-title":"Nat Commun"},{"issue":"8","key":"ppat.1010887.ref062","doi-asserted-by":"crossref","first-page":"e73783","DOI":"10.1371\/journal.pone.0073783","article-title":"Inducible Knockdown of Plasmodium Gene Expression Using the glmS Ribozyme.","volume":"8","author":"P Prommana","year":"2013","journal-title":"PLoS One"},{"issue":"7747","key":"ppat.1010887.ref063","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/s41586-019-0973-1","article-title":"Exposing Anopheles mosquitoes to antimalarials blocks Plasmodium parasite transmission","volume":"567","author":"DG Paton","year":"2019","journal-title":"Nature"},{"issue":"5","key":"ppat.1010887.ref064","doi-asserted-by":"crossref","first-page":"1188","DOI":"10.1021\/cb500071v","article-title":"A small molecule compound targeting STAT3 DNA-binding domain inhibits cancer cell proliferation, migration, and invasion.","volume":"9","author":"W Huang","year":"2014","journal-title":"ACS Chem Biol."},{"issue":"1","key":"ppat.1010887.ref065","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1038\/s41598-020-77644-4","article-title":"An integrated platform for genome engineering and gene expression perturbation in Plasmodium falciparum","volume":"11","author":"AS Nasamu","year":"2021","journal-title":"Sci Rep"},{"key":"ppat.1010887.ref066","first-page":"1","article-title":"The Plasmodium falciparum ABC transporter ABCI3 confers parasite strain-dependent pleiotropic antimalarial drug resistance","author":"JM Murithi","year":"2021","journal-title":"Cell Chem Biol"},{"issue":"11","key":"ppat.1010887.ref067","doi-asserted-by":"crossref","first-page":"e202101199","DOI":"10.26508\/lsa.202101199","article-title":"An extended DNA-free intranuclear compartment organizes centrosome microtubules in malaria parasites","volume":"4","author":"CS Simon","year":"2021","journal-title":"Life Sci Alliance"},{"issue":"3","key":"ppat.1010887.ref068","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1073\/pnas.93.3.1130","article-title":"Transformation of Plasmodium falciparum malaria parasites by homologous integration of plasmids that confer resistance to pyrimethamine","volume":"93","author":"Y Wu","year":"1996","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1010887.ref069","author":"R Huey","year":"2008","journal-title":"Using AutoDock 4 with AutoDockTools : A Tutorial."},{"issue":"4","key":"ppat.1010887.ref070","doi-asserted-by":"crossref","first-page":"1172","DOI":"10.1128\/AAC.01313-06","article-title":"Comparison of a SYBR green I-based assay with a histidine-rich protein II enzyme-linked immunosorbent assay for in vitro antimalarial drug efficacy testing and application to clinical isolates","volume":"51","author":"DJ Bacon","year":"2007","journal-title":"Antimicrob Agents Chemother"},{"issue":"9","key":"ppat.1010887.ref071","doi-asserted-by":"crossref","first-page":"1157","DOI":"10.1002\/jcc.20035","article-title":"Development and testing of a general Amber force field","volume":"25","author":"J Wang","year":"2004","journal-title":"J Comput Chem"},{"issue":"2","key":"ppat.1010887.ref072","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.jmgm.2005.12.005","article-title":"Automatic atom type and bond type perception in molecular mechanical calculations","volume":"25","author":"J Wang","year":"2006","journal-title":"J Mol Graph Model"},{"key":"ppat.1010887.ref073","first-page":"1503","article-title":"DAC. Antechamber: an accessory software package for molecular mechanical calculations","volume":"222","author":"J. Wang","year":"2001","journal-title":"J Am Chem Soc"},{"key":"ppat.1010887.ref074","unstructured":"Case, D., K. Belfon, I. Ben-Shalom, S. Brozell, D. Cerutti, T. Cheatham III, V. Cruzeiro, T. Darden, R. Duke, G. Giambasu, M. Gilson, H. Gohlke, A. Goetz, R. Harris, S. Izadi, S. Izmailov, K. Kasavajhala, A. Kovalenko, R. Krasny, T. Kurtzman, T. Lee, S. L DY and PK. AMBER 2020 [Internet]. University of California, San Francisco; 2020. Available from: https:\/\/ambermd.org\/doc12\/Amber20.pdf"},{"issue":"11","key":"ppat.1010887.ref075","doi-asserted-by":"crossref","first-page":"3817","DOI":"10.1529\/biophysj.106.097782","article-title":"Refinement of the AMBER force field for nucleic acids: Improving the description of \u03b1\/\u03b3 conformers","volume":"92","author":"A P\u00e9rez","year":"2007","journal-title":"Biophys J"},{"issue":"5","key":"ppat.1010887.ref076","doi-asserted-by":"crossref","first-page":"1542","DOI":"10.1021\/ct200909j","article-title":"Routine microsecond molecular dynamics simulations with AMBER on GPUs. 1. generalized born.","volume":"8","author":"AW G\u00f6tz","year":"2012","journal-title":"J Chem Theory Comput"},{"issue":"9","key":"ppat.1010887.ref077","doi-asserted-by":"crossref","first-page":"3878","DOI":"10.1021\/ct400314y","article-title":"Routine Microsecond Molecular Dynamics Simulations with AMBER on GPUs. 2. Explicit Solvent Particle Mesh EwaldNo Title.","volume":"10","author":"R Salomon-Ferrer","year":"2013","journal-title":"J Chem Theory Comput"},{"issue":"3","key":"ppat.1010887.ref078","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/0021-9991(77)90098-5","article-title":"Numerical integration of the cartesian equations of motion of a system with constraints: molecular dynamics of n-alkanes","volume":"23","author":"JP Ryckaert","year":"1977","journal-title":"J Comput Phys"},{"issue":"7","key":"ppat.1010887.ref079","first-page":"3084","article-title":"PTRAJ and CPPTRAJ: Software for processing and analysis of molecular dynamics trajectory data. J Chem Theory Comput","volume":"9","author":"DR Roe","year":"2013","journal-title":"Internet]"},{"issue":"17","key":"ppat.1010887.ref080","doi-asserted-by":"crossref","first-page":"3246","DOI":"10.1093\/bioinformatics\/bth349","article-title":"Java Treeview\u2014Extensible visualization of microarray data","volume":"20","author":"AJ Saldanha","year":"2004","journal-title":"Bioinformatics"},{"issue":"9","key":"ppat.1010887.ref081","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1093\/bioinformatics\/bth078","article-title":"Open source clustering software","volume":"20","author":"MJL de Hoon","year":"2004","journal-title":"Bioinformatics"},{"issue":"15","key":"ppat.1010887.ref082","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"AM Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ppat.1010887.ref083","author":"S. Andrews","year":"2010","journal-title":"FastQC: A Quality Control Tool for High Throughput Sequence Data"},{"issue":"00","key":"ppat.1010887.ref084","first-page":"1","volume":"00","author":"H. Li","year":"2013","journal-title":"Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM"},{"issue":"16","key":"ppat.1010887.ref085","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"H Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ppat.1010887.ref086","article-title":"Improved peak-calling with MACS2","author":"JM Gaspar","year":"2018","journal-title":"bioRxiv"},{"issue":"6","key":"ppat.1010887.ref087","doi-asserted-by":"crossref","first-page":"841","DOI":"10.1093\/bioinformatics\/btq033","article-title":"BEDTools: A flexible suite of utilities for comparing genomic features","volume":"26","author":"AR Quinlan","year":"2010","journal-title":"Bioinformatics"},{"issue":"W1","key":"ppat.1010887.ref088","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1093\/nar\/gku365","article-title":"DeepTools: A flexible platform for exploring deep-sequencing data","volume":"42","author":"F Ram\u00edrez","year":"2014","journal-title":"Nucleic Acids Res"},{"issue":"12","key":"ppat.1010887.ref089","doi-asserted-by":"crossref","first-page":"1653","DOI":"10.1093\/bioinformatics\/btr261","article-title":"DREME: Motif discovery in transcription factor ChIP-seq data","volume":"27","author":"TL Bailey","year":"2011","journal-title":"Bioinformatics"},{"issue":"7","key":"ppat.1010887.ref090","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1093\/bioinformatics\/btr064","article-title":"FIMO: Scanning for occurrences of a given motif","volume":"27","author":"CE Grant","year":"2011","journal-title":"Bioinformatics"},{"issue":"7457","key":"ppat.1010887.ref091","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1038\/nature12361","article-title":"PfSETvs methylation of histone H3K36 represses virulence genes in Plasmodium falciparum","volume":"499","author":"L Jiang","year":"2013","journal-title":"Nature"},{"issue":"9","key":"ppat.1010887.ref092","doi-asserted-by":"crossref","first-page":"e1007329","DOI":"10.1371\/journal.pcbi.1007329","article-title":"Predicting gene expression in the human malaria parasite Plasmodium falciparum using histone modification, nucleosome positioning, and 3D localization features.","volume":"15","author":"DF Read","year":"2019","journal-title":"PLoS Comput Biol"},{"issue":"1","key":"ppat.1010887.ref093","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1186\/1471-2164-15-347","article-title":"DNA-encoded nucleosome occupancy is associated with transcription levels in the human malaria parasite Plasmodium falciparum","volume":"15","author":"EM Bunnik","year":"2014","journal-title":"BMC Genomics"},{"issue":"3","key":"ppat.1010887.ref094","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.chom.2018.01.008","article-title":"Comparative Heterochromatin Profiling Reveals Conserved and Unique Epigenome Signatures Linked to Adaptation and Development of Malaria Parasites.","volume":"23","author":"SA Fraschka","year":"2018","journal-title":"Cell Host Microbe"},{"issue":"11","key":"ppat.1010887.ref095","doi-asserted-by":"crossref","first-page":"R108","DOI":"10.1186\/gb-2012-13-11-r108","article-title":"Organellar proteomics reveals hundreds of novel nuclear proteins in the malaria parasite Plasmodium falciparum","volume":"13","author":"SC Oehring","year":"2012","journal-title":"Genome Biol"},{"issue":"1\u20132","key":"ppat.1010887.ref096","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.bbagrm.2009.09.008","article-title":"HMGB proteins: Interactions with DNA and chromatin","volume":"1799","author":"M. \u0160tros","year":"2010","journal-title":"Biochim Biophys Acta\u2014Gene Regul Mech"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1010887","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2022,10,24]],"date-time":"2022-10-24T00:00:00Z","timestamp":1666569600000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010887","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T20:37:25Z","timestamp":1701203845000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1010887"}},"subtitle":[],"editor":[{"given":"Laura J.","family":"Knoll","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2022,10,12]]},"references-count":96,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2022,10,12]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1010887","relation":{"new_version":[{"id-type":"doi","id":"10.1371\/journal.ppat.1010887","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,12]]}}}