{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T13:39:03Z","timestamp":1786714743879,"version":"build-2736575974"},"reference-count":109,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2023\/07746-0"],"award-info":[{"award-number":["2023\/07746-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2026\/13323-2"],"award-info":[{"award-number":["2026\/13323-2"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2024\/18787-1"],"award-info":[{"award-number":["2024\/18787-1"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2023\/08379-0"],"award-info":[{"award-number":["2023\/08379-0"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"S\u00e3o Paulo Research Foundation","doi-asserted-by":"publisher","award":["2024\/14768-2"],"award-info":[{"award-number":["2024\/14768-2"]}],"id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"award":["2023\/07746-0"],"award-info":[{"award-number":["2023\/07746-0"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2026\/13323-2"],"award-info":[{"award-number":["2026\/13323-2"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2024\/18787-1"],"award-info":[{"award-number":["2024\/18787-1"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2023\/08379-0"],"award-info":[{"award-number":["2023\/08379-0"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]},{"award":["2024\/14768-2"],"award-info":[{"award-number":["2024\/14768-2"]}],"id":[{"id":"https:\/\/ror.org\/02ddkpn78","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["88887.923812\/2023-00"],"award-info":[{"award-number":["88887.923812\/2023-00"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]},{"award":["88887.923812\/2023-00"],"award-info":[{"award-number":["88887.923812\/2023-00"]}],"id":[{"id":"https:\/\/ror.org\/00x0ma614","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Malaria remains a major global health problem, especially in low- and mid-income countries where Plasmodium parasites are commonly endemic. Despite the significant number of available drugs to treat the disease, some aspects, such as increasing resistance to frontline antimalarials, inefficient treatment of asymptomatic carriers and treatment inadequacy for certain vulnerable groups, are jeopardizing control measures, justifying the need for therapeutic targets driving the discovery of new compounds. In this context, glutathione transferases, which are essential for redox metabolism and detoxification of heme in the asexual blood stages of Plasmodium parasites, have emerged as promising targets more than two decades ago, but have been deprioritized due to significant gaps in research. This review aims to synthesize current biochemical, structural, genetic, and transcriptomic evidence on Plasmodium glutathione S-transferases and evaluate their role in parasite physiology across the life cycle while revising their potential for drug targeting using suggested guidelines for target candidate profiling and prioritization.<\/jats:p>","DOI":"10.3390\/ph19081287","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T13:12:56Z","timestamp":1786713176000},"page":"1287","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Revisiting Glutathione Transferases of Plasmodium as Potential Targets for Coadjuvant Therapies and the Development of New Antimalarials"],"prefix":"10.3390","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7379-6351","authenticated-orcid":false,"given":"Maria Luiza","family":"Lima","sequence":"first","affiliation":[{"name":"Department of Parasitology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, Av. Prof. Lineu Prestes 1374, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-8148-7096","authenticated-orcid":false,"given":"Nele","family":"Wild","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, Av. Prof. Lineu Prestes 1374, S\u00e3o Paulo 05508-000, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9119-6560","authenticated-orcid":false,"given":"Eva","family":"Liebau","sequence":"additional","affiliation":[{"name":"Institute of Integrated Cell Biology and Physiology, University of M\u00fcnster, Schlossplatz 8, D-48143 M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5987-1749","authenticated-orcid":false,"given":"Carsten","family":"Wrenger","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, Av. Prof. Lineu Prestes 1374, S\u00e3o Paulo 05508-000, Brazil"},{"name":"Institut Pasteur de S\u00e3o Paulo, Av. Prof. L\u00facio Martins Rodrigues 370, S\u00e3o Paulo 05508-020, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2280-6991","authenticated-orcid":false,"given":"Andr\u00e9","family":"Barateiro","sequence":"additional","affiliation":[{"name":"Department of Parasitology, Institute of Biomedical Sciences, University of S\u00e3o Paulo, Av. Prof. Lineu Prestes 1374, S\u00e3o Paulo 05508-000, Brazil"},{"name":"Institut Pasteur de S\u00e3o Paulo, Av. Prof. L\u00facio Martins Rodrigues 370, S\u00e3o Paulo 05508-020, Brazil"},{"name":"Center for Tropical and Emerging Global Diseases, University of Georgia, 500 D. W. Brooks Drive, Athens, GA 30605, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1016\/S0140-6736(23)01249-7","article-title":"Malaria","volume":"402","author":"Poespoprodjo","year":"2023","journal-title":"Lancet"},{"key":"ref_2","unstructured":"World Health Organization (2025). World Malaria Report 2025: Addressing the Threat of Antimalarial Drug Resistance, WHO."},{"key":"ref_3","unstructured":"World Health Organization (2016). Global Technical Strategy for Malaria 2016\u20132030, WHO."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1038\/nrmicro.2017.161","article-title":"Drug Resistance in Plasmodium","volume":"16","author":"Haldar","year":"2018","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1038\/nm.4381","article-title":"Antimalarial Drug Resistance: Linking Plasmodium falciparum Parasite Biology to the Clinic","volume":"23","author":"Blasco","year":"2017","journal-title":"Nat. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2619","DOI":"10.1056\/NEJMc0805011","article-title":"Evidence of Artemisinin-Resistant Malaria in Western Cambodia","volume":"359","author":"Noedl","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1186\/1475-2875-13-452","article-title":"Artemisinin Resistance\u2014Modelling the Potential Human and Economic Costs","volume":"13","author":"Lubell","year":"2014","journal-title":"Malar. J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e00011-19","DOI":"10.1128\/CMR.00011-19","article-title":"8-Aminoquinoline Therapy for Latent Malaria","volume":"32","author":"Baird","year":"2019","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/d41573-025-00193-w","article-title":"Novel Antimalarial Passes Key Phase III Test","volume":"25","author":"Mullard","year":"2026","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2764","DOI":"10.1021\/acsinfecdis.1c00322","article-title":"Prioritization of Molecular Targets for Antimalarial Drug Discovery","volume":"7","author":"Forte","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.ijpara.2003.09.011","article-title":"Oxidative Stress in Malaria Parasite-Infected Erythrocytes: Host\u2013Parasite Interactions","volume":"34","author":"Becker","year":"2004","journal-title":"Int. J. Parasitol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Egwu, C.O., Augereau, J.-M., Reybier, K., and Benoit-Vical, F. (2021). Reactive Oxygen Species as the Brainbox in Malaria Treatment. Antioxidants, 10.","DOI":"10.3390\/antiox10121872"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s00436-021-07051-9","article-title":"Redox Interactome in Malaria Parasite Plasmodium falciparum","volume":"120","author":"Tiwari","year":"2021","journal-title":"Parasitol. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"10511","DOI":"10.3390\/molecules200610511","article-title":"Role and Regulation of Glutathione Metabolism in Plasmodium falciparum","volume":"20","year":"2015","journal-title":"Molecules"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"516","DOI":"10.1042\/bj0790516","article-title":"An Enzyme from Rat Liver Catalysing Conjugations with Glutathione","volume":"79","author":"Booth","year":"1961","journal-title":"Biochem. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1146\/annurev.pharmtox.45.120403.095857","article-title":"Glutathione Transferases","volume":"45","author":"Hayes","year":"2005","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"150774","DOI":"10.1016\/j.bbrc.2024.150774","article-title":"Glutathione S-Transferase: A Versatile and Dynamic Enzyme","volume":"734","author":"Aloke","year":"2024","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"138","DOI":"10.3109\/03602532.2011.558093","article-title":"Glutathione Transferases: A Structural Perspective","volume":"43","author":"Oakley","year":"2011","journal-title":"Drug Metab. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.tips.2012.09.007","article-title":"Human Cytosolic Glutathione Transferases: Structure, Function, and Drug Discovery","volume":"33","author":"Wu","year":"2012","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0076-6879(05)01001-3","article-title":"Nomenclature for Mammalian Soluble Glutathione Transferases","volume":"Volume 401","author":"Mannervik","year":"2005","journal-title":"Methods in Enzymology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1186\/1479-7364-1-6-460","article-title":"Analysis of the Glutathione S-Transferase (GST) Gene Family","volume":"1","author":"Nebert","year":"2004","journal-title":"Hum. Genom."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1097\/00008571-200206000-00003","article-title":"The Human Glutathione Transferase Alpha Locus: Genomic Organization of the Gene Cluster and Functional Characterization of the Genetic Polymorphism in the HGSTA1 Promoter","volume":"12","author":"Morel","year":"2002","journal-title":"Pharmacogenetics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1006\/abbi.1998.0964","article-title":"Distinctive Structure of the HumanGSTM3Gene\u2014Inverted Orientation Relative to the Mu Class Glutathione Transferase Gene Cluster","volume":"361","author":"Patskovsky","year":"1999","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/0022-2836(92)90692-D","article-title":"Three-Dimensional Structure of Class \u03c0 Glutathione S-Transferase from Human Placenta in Complex with S-Hexylglutathione at 2.8 \u00c5 Resolution","volume":"227","author":"Reinemer","year":"1992","journal-title":"J. Mol. Biol."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Armstrong, R.N., Morgenstern, R., and Board, P.G. (2018). Glutathione Transferases, Elsevier. [3rd ed.].","DOI":"10.1016\/B978-0-12-801238-3.64296-4"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1567","DOI":"10.1021\/bi002249z","article-title":"Crystal Structure of Maleylacetoacetate Isomerase\/Glutathione Transferase Zeta Reveals the Molecular Basis for Its Remarkable Catalytic Promiscuity","volume":"40","author":"Polekhina","year":"2001","journal-title":"Biochemistry"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1093\/protein\/15.10.827","article-title":"Design of a Monomeric Human Glutathione Transferase GSTP1, a Structurally Stable but Catalytically Inactive Protein","volume":"15","author":"Abdalla","year":"2002","journal-title":"Protein Eng. Des. Sel."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/S0969-2126(98)00034-3","article-title":"Human Theta Class Glutathione Transferase: The Crystal Structure Reveals a Sulfate-Binding Pocket within a Buried Active Site","volume":"6","author":"Rossjohn","year":"1998","journal-title":"Structure"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1080\/14756360601072676","article-title":"Synthesis and Biological Evaluation of Potential Modulators of Malarial Glutathione-S-Transferase(S)","volume":"22","author":"Ahmad","year":"2007","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1007\/s00436-007-0836-9","article-title":"Inhibition of Glutathione-S-Transferase from Plasmodium Yoelii by Protoporphyrin IX, Cibacron Blue and Menadione: Implications and Therapeutic Benefits","volume":"102","author":"Ahmad","year":"2008","journal-title":"Parasitol. Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1006\/expr.1995.1099","article-title":"Plasmodium Berghei: Implication of Intracellular Glutathione and Its Related Enzyme in Chloroquine Resistance in Vivo","volume":"81","author":"Dubois","year":"1995","journal-title":"Exp. Parasitol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1515\/BC.2002.086","article-title":"Glutathione S-Transferase of the Malarial Parasite Plasmodium falciparum: Characterization of a Potential Drug Target","volume":"383","author":"Harwaldt","year":"2002","journal-title":"Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1046\/j.1365-3156.1999.00387.x","article-title":"Glutathione-S-transferase Activity in Malarial Parasites","volume":"4","author":"Srivastava","year":"1999","journal-title":"Trop. Med. Int. Health"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1016\/S0166-6851(98)00170-4","article-title":"Role of Glutathione in the Detoxification of Ferriprotoporphyrin IX in Chloroquine Resistant Plasmodium Berghei","volume":"98","author":"Platel","year":"1999","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_35","first-page":"e01643-23","article-title":"Novel Hydrazone Compounds with Broad-Spectrum Antiplasmodial Activity and Synergistic Interactions with Antimalarial Drugs","volume":"68","author":"Pala","year":"2024","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"22133","DOI":"10.1074\/jbc.M109.015198","article-title":"Tetramerization and Cooperativity in Plasmodium falciparum Glutathione S-Transferase Are Mediated by Atypic Loop 113\u2013119","volume":"284","author":"Liebau","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"13821","DOI":"10.1073\/pnas.2333763100","article-title":"X-Ray Structure of Glutathione S-Transferase from the Malarial Parasite Plasmodium falciparum","volume":"100","author":"Becker","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"854","DOI":"10.3109\/14756366.2010.486793","article-title":"Glutathione Transferase from Plasmodium falciparum\u2014Interaction with Malagashanine and Selected Plant Natural Products","volume":"25","author":"Mangoyi","year":"2010","journal-title":"J. Enzym. Inhib. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"140526","DOI":"10.1016\/j.ijbiomac.2025.140526","article-title":"High-Throughput Virtual Screening and Empirical Validation of Probable Inhibitors of Plasmodium falciparum and Vivax Glutathione Transferase Using Bromosulfophthalein as the Benchmark Ligand","volume":"302","author":"Onisuru","year":"2025","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"26121","DOI":"10.1074\/jbc.M503889200","article-title":"Cooperativity and Pseudo-Cooperativity in the Glutathione S-Transferase from Plasmodium falciparum","volume":"280","author":"Liebau","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0166-6851(02)00160-3","article-title":"The Glutathione S-Transferase from Plasmodium falciparum","volume":"124","author":"Liebau","year":"2002","journal-title":"Mol. Biochem. Parasitol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"7696","DOI":"10.1080\/07391102.2024.2329291","article-title":"Describing the Ligandin Properties of Plasmodium falciparum and Vivax Glutathione Transferase towards Bromosulfophthalein from Empirical and Computational Modelling Viewpoints","volume":"43","author":"Onisuru","year":"2025","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1016\/j.exppara.2007.02.005","article-title":"Plasmodium vivax: Molecular Cloning, Expression and Characterization of Glutathione S-Transferase","volume":"116","author":"Na","year":"2007","journal-title":"Exp. Parasitol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.abb.2009.05.011","article-title":"Structural, Functional and Unfolding Characteristics of Glutathione S-Transferase of Plasmodium vivax","volume":"487","author":"Tripathi","year":"2009","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"D808","DOI":"10.1093\/nar\/gkad1003","article-title":"VEuPathDB: The Eukaryotic Pathogen, Vector and Host Bioinformatics Resource Center in 2023","volume":"52","author":"Amos","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1110\/ps.051891106","article-title":"Plasmodium falciparum Glutathione S-transferase\u2014Structural and Mechanistic Studies on Ligand Binding and Enzyme Inhibition","volume":"15","author":"Hiller","year":"2006","journal-title":"Protein Sci."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1016\/S0076-6879(05)01015-3","article-title":"Glutathione S-transferase from Malarial Parasites: Structural and Functional Aspects","volume":"Volume 401","author":"Deponte","year":"2005","journal-title":"Methods in Enzymology"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1016\/j.jsb.2015.06.008","article-title":"High Resolution Structures of Plasmodium falciparum GST Complexes Provide Novel Insights into the Dimer\u2013Tetramer Transition and a Novel Ligand-Binding Site","volume":"191","author":"Perbandt","year":"2015","journal-title":"J. Struct. Biol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1074\/jbc.M309663200","article-title":"Native and Inhibited Structure of a Mu Class-Related Glutathione S-Transferase from Plasmodium falciparum","volume":"279","author":"Perbandt","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Tripathi, T., Rahlfs, S., Becker, K., and Bhakuni, V. (2007). Glutathione Mediated Regulation of Oligomeric Structure and Functional Activity of Plasmodium falciparum Glutathione S-Transferase. BMC Struct. Biol., 7.","DOI":"10.1186\/1472-6807-7-67"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1016\/j.bbapap.2014.04.017","article-title":"Asn112 in Plasmodium falciparum Glutathione S-Transferase Is Essential for Induced Reversible Tetramerization by Phosphate or Pyrophosphate","volume":"1844","year":"2014","journal-title":"Biochim. Biophys. Acta-Proteins Proteom."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"916","DOI":"10.1016\/j.cell.2014.07.011","article-title":"Supergenomic Network Compression and the Discovery of EXP1 as a Glutathione Transferase Inhibited by Artesunate","volume":"158","author":"Lisewski","year":"2014","journal-title":"Cell"},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Mes\u00e9n-Ram\u00edrez, P., Bergmann, B., Tran, T.T., Garten, M., St\u00e4cker, J., Naranjo-Prado, I., H\u00f6hn, K., Zimmerberg, J., and Spielmann, T. (2019). EXP1 Is Critical for Nutrient Uptake across the Parasitophorous Vacuole Membrane of Malaria Parasites. PLoS Biol., 17.","DOI":"10.1371\/journal.pbio.3000473"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/j.ijpddr.2017.12.003","article-title":"Potential Role of Plasmodium falciparum Exported Protein 1 in the Chloroquine Mode of Action","volume":"8","author":"Lisewski","year":"2018","journal-title":"Int. J. Parasitol. Drugs Drug Resist."},{"key":"ref_55","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":"Zhang","year":"2018","journal-title":"Science"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.cell.2008.04.051","article-title":"Exported Proteins Required for Virulence and Rigidity of Plasmodium falciparum-Infected Human Erythrocytes","volume":"134","author":"Maier","year":"2008","journal-title":"Cell"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e13168","DOI":"10.1111\/cmi.13168","article-title":"EXP1 Is Required for Organisation of EXP2 in the Intraerythrocytic Malaria Parasite Vacuole","volume":"22","author":"Nessel","year":"2020","journal-title":"Cell. Microbiol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"758","DOI":"10.1016\/j.pt.2022.05.014","article-title":"In Vitro Models for Human Malaria: Targeting the Liver Stage","volume":"38","author":"Valenciano","year":"2022","journal-title":"Trends Parasitol."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Joyner, C., Barnwell, J.W., and Galinski, M.R. (2015). No More Monkeying around: Primate Malaria Model Systems Are Key to Understanding Plasmodium vivax Liver-Stage Biology, Hypnozoites, and Relapses. Front. Microbiol., 6.","DOI":"10.3389\/fmicb.2015.00145"},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Voorberg-van der Wel, A., Kocken, C.H.M., and Zeeman, A.M. (2021). Modeling Relapsing Malaria: Emerging Technologies to Study Parasite-Host Interactions in the Liver. Front. Cell. Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.606033"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/nrg3456","article-title":"Functional and Evolutionary Implications of Gene Orthology","volume":"14","author":"Koonin","year":"2013","journal-title":"Nat. Rev. Genet."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e03234-19","DOI":"10.1128\/mBio.03234-19","article-title":"RNA-Seq Analysis Illuminates the Early Stages of Plasmodium Liver Infection","volume":"11","author":"Sylvester","year":"2020","journal-title":"mBio"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1186\/s12936-019-2968-7","article-title":"Transcriptome Analysis of Plasmodium berghei during Exo-Erythrocytic Development","volume":"18","author":"Caldelari","year":"2019","journal-title":"Malar. J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"2763","DOI":"10.1038\/s41467-020-16593-y","article-title":"Malaria Parasites Regulate Intra-Erythrocytic Development Duration via Serpentine Receptor 10 to Coordinate with Host Rhythms","volume":"11","author":"Subudhi","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1186\/s12936-020-03436-w","article-title":"A Comprehensive RNA Handling and Transcriptomics Guide for High-Throughput Processing of Plasmodium Blood-Stage Samples","volume":"19","author":"Kucharski","year":"2020","journal-title":"Malar. J."},{"key":"ref_66","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":"Toenhake","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_67","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":"Llinas","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"B\u00e1rtfai, R., Hoeijmakers, W.A.M., Salcedo-Amaya, A.M., Smits, A.H., Janssen-Megens, E., Kaan, A., Treeck, M., Gilberger, T.-W., Fran\u00e7oijs, K.-J., and Stunnenberg, H.G. (2010). H2A.Z Demarcates Intergenic Regions of the Plasmodium falciparum Epigenome That Are Dynamically Marked by H3K9ac and H3K4me3. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1001223"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1111\/j.1365-2958.2009.07026.x","article-title":"New Insights into the Blood-stage Transcriptome of Plasmodium falciparum Using RNA-Seq","volume":"76","author":"Otto","year":"2010","journal-title":"Mol. Microbiol."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Siegel, T., Hon, C.-C., Zhang, Q., Lopez-Rubio, J.-J., Scheidig-Benatar, C., Martins, R.M., Sismeiro, O., Copp\u00e9e, J.-Y., and Scherf, A. (2014). Strand-Specific RNA-Seq Reveals Widespread and Developmentally Regulated Transcription of Natural Antisense Transcripts in Plasmodium falciparum. BMC Genom., 15.","DOI":"10.1186\/1471-2164-15-150"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e01500-19","DOI":"10.1128\/mBio.01500-19","article-title":"Dissecting the Gene Expression, Localization, Membrane Topology, and Function of the Plasmodium falciparum STEVOR Protein Family","volume":"10","author":"Wichers","year":"2019","journal-title":"mBio"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Chappell, L., Ross, P., Orchard, L., Russell, T.J., Otto, T.D., Berriman, M., Rayner, J.C., and Llin\u00e1s, M. (2020). Refining the Transcriptome of the Human Malaria Parasite Plasmodium falciparum Using Amplification-Free RNA-Seq. BMC Genom., 21.","DOI":"10.1186\/s12864-020-06787-5"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"20498","DOI":"10.1038\/srep20498","article-title":"New Insights into the Plasmodium vivax Transcriptome Using RNA-Seq","volume":"6","author":"Zhu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Otto, T.D., B\u00f6hme, U., Jackson, A.P., Hunt, M., Franke-Fayard, B., Hoeijmakers, W.A.M., Religa, A.A., Robertson, L., Sanders, M., and Ogun, S.A. (2014). A Comprehensive Evaluation of Rodent Malaria Parasite Genomes and Gene Expression. BMC Biol., 12.","DOI":"10.1186\/s12915-014-0086-0"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1100","DOI":"10.1128\/AAC.01175-08","article-title":"In Vitro and In Vivo Properties of Ellagic Acid in Malaria Treatment","volume":"53","author":"Soh","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1128\/AAC.00544-08","article-title":"Compounds Structurally Related to Ellagic Acid Show Improved Antiplasmodial Activity","volume":"53","author":"Sturm","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"4964","DOI":"10.1038\/s41467-019-12936-6","article-title":"Transcriptomics and Proteomics Reveal Two Waves of Translational Repression during the Maturation of Malaria Parasite Sporozoites","volume":"10","author":"Lindner","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_78","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":"Vembar","year":"2018","journal-title":"Cell Rep."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"12183","DOI":"10.1038\/s41598-018-30713-1","article-title":"Unraveling the Plasmodium vivax Sporozoite Transcriptional Journey from Mosquito Vector to Human Host","volume":"8","author":"Roth","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1016\/j.ijpara.2019.02.007","article-title":"Transcriptome and Histone Epigenome of Plasmodium vivax Salivary-Gland Sporozoites Point to Tight Regulatory Control and Mechanisms for Liver-Stage Differentiation in Relapsing Malaria","volume":"49","author":"Muller","year":"2019","journal-title":"Int. J. Parasitol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"40655","DOI":"10.1038\/srep40655","article-title":"Epigenetic Regulation of Plasmodium falciparum Clonally Variant Gene Expression during Development in Anopheles Gambiae","volume":"7","author":"Yerbanga","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.1016\/j.cell.2019.10.030","article-title":"Genome-Scale Identification of Essential Metabolic Processes for Targeting the Plasmodium Liver Stage","volume":"179","author":"Stanway","year":"2019","journal-title":"Cell"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1038\/s41467-019-08349-0","article-title":"Dual RNA-Seq Identifies Human Mucosal Immunity Protein Mucin-13 as a Hallmark of Plasmodium Exoerythrocytic Infection","volume":"10","author":"LaMonte","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.chom.2018.01.002","article-title":"In Vitro Culture, Drug Sensitivity, and Transcriptome of Plasmodium vivax Hypnozoites","volume":"23","author":"Gural","year":"2018","journal-title":"Cell Host Microbe"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"e29605","DOI":"10.7554\/eLife.29605","article-title":"A Comparative Transcriptomic Analysis of Replicating and Dormant Liver Stages of the Relapsing Malaria Parasite Plasmodium cynomolgi","volume":"6","author":"Roma","year":"2017","journal-title":"eLife"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e12735","DOI":"10.1111\/cmi.12735","article-title":"Laser Capture Microdissection Enables Transcriptomic Analysis of Dividing and Quiescent Liver Stages of Plasmodium Relapsing Species","volume":"19","author":"Cubi","year":"2017","journal-title":"Cell. Microbiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"6087","DOI":"10.1093\/nar\/gkw536","article-title":"Integrated Transcriptomic and Proteomic Analyses of P. falciparum Gametocytes: Molecular Insight into Sex-Specific Processes and Translational Repression","volume":"44","author":"Lasonder","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"L\u00f3pez-Barrag\u00e1n, M.J., Lemieux, J., Qui\u00f1ones, M., Williamson, K.C., Molina-Cruz, A., Cui, K., Barillas-Mury, C., Zhao, K., and Su, X. (2011). Directional Gene Expression and Antisense Transcripts in Sexual and Asexual Stages of Plasmodium falciparum. BMC Genom., 12.","DOI":"10.1186\/1471-2164-12-587"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1074\/mcp.M116.061804","article-title":"Sex-Specific Biology of the Human Malaria Parasite Revealed from the Proteomes of Mature Male and Female Gametocytes","volume":"16","author":"Miao","year":"2017","journal-title":"Mol. Cell. Proteom."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Yeoh, L.M., Goodman, C.D., Mollard, V., McFadden, G.I., and Ralph, S.A. (2017). Comparative Transcriptomics of Female and Male Gametocytes in Plasmodium berghei and the Evolution of Sex in Alveolates. BMC Genom., 18.","DOI":"10.1186\/s12864-017-4100-0"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.jsb.2011.09.003","article-title":"Soft X-Ray Microscopy Analysis of Cell Volume and Hemoglobin Content in Erythrocytes Infected with Asexual and Sexual Stages of Plasmodium falciparum","volume":"177","author":"Hanssen","year":"2012","journal-title":"J. Struct. Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1111\/mmi.13626","article-title":"A High Susceptibility to Redox Imbalance of the Transmissible Stages of Plasmodium falciparum Revealed with a Luciferase-based Mature Gametocyte Assay","volume":"104","author":"Siciliano","year":"2017","journal-title":"Mol. Microbiol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1186\/1475-2875-12-187","article-title":"Designing the next Generation of Medicines for Malaria Control and Eradication","volume":"12","author":"Burrows","year":"2013","journal-title":"Malar. J."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Col\u00f3n-Lorenzo, E.E., Col\u00f3n-L\u00f3pez, D.D., Vega-Rodr\u00edguez, J., Dupin, A., Fidock, D.A., Baerga-Ortiz, A., Ortiz, J.G., Bosch, J., and Serrano, A.E. (2020). Structure-Based Screening of Plasmodium berghei Glutathione S-Transferase Identifies CB-27 as a Novel Antiplasmodial Compound. Front. Pharmacol., 11.","DOI":"10.3389\/fphar.2020.00246"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Kudyba, H.M., Cobb, D.W., Vega-Rodr\u00edguez, J., and Muralidharan, V. (2021). Some Conditions Apply: Systems for Studying Plasmodium falciparum Protein Function. PLoS Pathog., 17.","DOI":"10.1371\/journal.ppat.1009442"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.cell.2017.06.030","article-title":"Functional Profiling of a Plasmodium Genome Reveals an Abundance of Essential Genes","volume":"170","author":"Bushell","year":"2017","journal-title":"Cell"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"12808","DOI":"10.1080\/07391102.2023.2175378","article-title":"Multi-Target Molecular Dynamic Simulations Reveal Glutathione-S-Transferase as the Most Favorable Drug Target of Knipholone in Plasmodium falciparum","volume":"41","author":"Sarma","year":"2023","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_98","first-page":"8486021","article-title":"Exploring the Infectious Drug Target Glutathione S-Transferase in Plasmodium falciparum with the Inhibitory Potential of Azadirachta indica Phytocompounds","volume":"2024","year":"2024","journal-title":"Adv. Public Health"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1007\/s00894-023-05650-0","article-title":"Development and Application of Fragment-Based de Novo Inhibitor Design Approaches against Plasmodium falciparum GST","volume":"29","author":"Mordi","year":"2023","journal-title":"J. Mol. Model."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.compbiolchem.2016.07.007","article-title":"Assembly of Ligands Interaction Models for Glutathione-S-Transferases from Plasmodium falciparum, Human and Mouse Using Enzyme Kinetics and Molecular Docking","volume":"64","author":"Mordi","year":"2016","journal-title":"Comput. Biol. Chem."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1021\/acsinfecdis.5b00143","article-title":"High-Throughput Luciferase-Based Assay for the Discovery of Therapeutics That Prevent Malaria","volume":"2","author":"Swann","year":"2016","journal-title":"ACS Infect. Dis."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1186\/s12936-024-05155-y","article-title":"Screening the Global Health Priority Box against Plasmodium berghei Liver Stage Parasites Using an Inexpensive Luciferase Detection Protocol","volume":"23","author":"Nguyen","year":"2024","journal-title":"Malar. J."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1021\/np000306j","article-title":"In Vitro Antiplasmodial Activity of Extracts of Tristaniopsis Species and Identification of the Active Constituents: Ellagic Acid and 3,4,5-Trimethoxyphenyl-(6\u2018-O-Galloyl)-O-\u03b2-d-Glucopyranoside","volume":"64","author":"Verotta","year":"2001","journal-title":"J. Nat. Prod."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/S0378-8741(02)00121-6","article-title":"In Vitro Antiplasmodial Activity of Extracts of Alchornea Cordifolia and Identification of an Active Constituent: Ellagic Acid","volume":"81","author":"Banzouzi","year":"2002","journal-title":"J. Ethnopharmacol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1980","DOI":"10.1021\/bi400007g","article-title":"Calorimetric Studies of Ligands Binding to Glutathione S-Transferase from the Malarial Parasite Plasmodium falciparum","volume":"52","author":"Aguilera","year":"2013","journal-title":"Biochemistry"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1016\/j.pt.2021.04.006","article-title":"Assessing Risks of Plasmodium falciparum Resistance to Select Next-Generation Antimalarials","volume":"37","author":"Duffey","year":"2021","journal-title":"Trends Parasitol."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1038\/s41389-017-0025-3","article-title":"Glutathione Transferases: Substrates, Inihibitors and pro-Drugs in Cancer and Neurodegenerative Diseases","volume":"7","author":"Allocati","year":"2018","journal-title":"Oncogenesis"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1007\/s12223-025-01410-0","article-title":"Glutathione Redox System as a Therapeutic Target for Plasmodium: Opportunities, Challenges, and Future Perspectives","volume":"71","author":"Mahato","year":"2026","journal-title":"Folia Microbiol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"ovaf100","DOI":"10.1093\/lambio\/ovaf100","article-title":"Targeting Plasmodium Glutathione S-Transferases to Overcome Antimalaria Drug Resistance in Southern Africa","volume":"78","author":"Otun","year":"2025","journal-title":"Lett. Appl. Microbiol."}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/8\/1287\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T13:15:57Z","timestamp":1786713357000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/19\/8\/1287"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,14]]},"references-count":109,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["ph19081287"],"URL":"https:\/\/doi.org\/10.3390\/ph19081287","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,14]]}}}