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Five plasmodial species of <jats:italic>P. falciparum<\/jats:italic> <jats:italic>(Pf)<\/jats:italic>, <jats:italic>P. knowlesi<\/jats:italic>, <jats:italic>P. malariae<\/jats:italic>, <jats:italic>P. ovale<\/jats:italic>, and <jats:italic>P. vivax<\/jats:italic> <jats:italic>(Pv)<\/jats:italic> are responsible for causing malaria in humans. According to the World Malaria Report 2020, there were 229 million cases and\u2009~\u20090.04 million deaths of which 67% were in children below 5\u2009years of age. While more than 3 billion people are at risk of malaria infection globally, antimalarial drugs are their only option for treatment. Antimalarial drug resistance keeps arising periodically and thus threatens the main line of malaria treatment, emphasizing the need to find new alternatives. The availability of whole genomes of <jats:italic>P. falciparum<\/jats:italic> and <jats:italic>P. vivax<\/jats:italic> has allowed targeting their unexplored plasmodial enzymes for inhibitor development with a focus on multistage targets that are crucial for parasite viability in both the blood and liver stages. Over the past decades, aminoacyl\u2010tRNA synthetases (aaRSs) have been explored as anti\u2010bacterial and anti\u2010fungal drug targets, and more recently (since 2009) aaRSs are also the focus of antimalarial drug targeting. Here, we dissect the structure\u2010based knowledge of the most advanced three aaRSs\u2014lysyl\u2010 (KRS), prolyl\u2010 (PRS), and phenylalanyl\u2010 (FRS) synthetases in terms of development of antimalarial drugs. These examples showcase the promising potential of this family of enzymes to provide druggable targets that stall protein synthesis upon inhibition and thereby kill malaria parasites selectively.<\/jats:p>","DOI":"10.1002\/pro.4148","type":"journal-article","created":{"date-parts":[[2021,6,29]],"date-time":"2021-06-29T02:40:36Z","timestamp":1624934436000},"page":"1793-1803","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Structural analyses of the malaria parasite <scp>aminoacyl\u2010tRNA<\/scp> synthetases provide new avenues for antimalarial drug discovery"],"prefix":"10.1002","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4654-5463","authenticated-orcid":false,"given":"Jyoti","family":"Chhibber\u2010Goel","sequence":"first","affiliation":[{"name":"Structural Parasitology Group, Molecular Medicine International Center for Genetic Engineering and Biotechnology  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manickam","family":"Yogavel","sequence":"additional","affiliation":[{"name":"Structural Parasitology Group, Molecular Medicine International Center for Genetic Engineering and Biotechnology  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3305-0034","authenticated-orcid":false,"given":"Amit","family":"Sharma","sequence":"additional","affiliation":[{"name":"Structural Parasitology Group, Molecular Medicine International Center for Genetic Engineering and Biotechnology  New Delhi India"},{"name":"ICMR\u2010National Institute of Malaria Research  New Delhi India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,8,19]]},"reference":[{"key":"e_1_2_5_2_1","unstructured":"World Heath Organization.World Malaria Report.73 1\u20134(2020)."},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1086\/322858"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2019.10.001"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2020.12.011"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2018.08.006"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2018.168"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2021.01.009"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01097"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpddr.2013.10.001"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12936-019-2665-6"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpara.2011.11.008"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/21655979.2016.1149270"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drudis.2018.01.050"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-10-644"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444902003451"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.str.2016.06.018"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0066224"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00820-16"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molbiopara.2013.04.007"},{"key":"e_1_2_5_21_1","first-page":"1575","article-title":"Conformational changes in glutaminyl\u2010tRNA synthetases upon binding of the substrates\u2009and analogs using molecular docking and molecular dynamics approaches","volume":"38","author":"Nachiappan M","year":"2020","journal-title":"J Biomol Struct Dyn."},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.278.5340.1119"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.2.418"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.67.4.550-573.2003"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0500226102"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0712072105"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1100224108"},{"key":"e_1_2_5_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2012.04.015"},{"key":"e_1_2_5_29_1","doi-asserted-by":"publisher","DOI":"10.1038\/srep19981"},{"key":"e_1_2_5_30_1","doi-asserted-by":"publisher","DOI":"10.1107\/S0907444913001923"},{"key":"e_1_2_5_31_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10969-014-9182-1"},{"key":"e_1_2_5_32_1","doi-asserted-by":"crossref","unstructured":"Changeux J.\u2010P.&Edelstein S.Conformational selection or induced fit? 50\u2009years of debate resolved. 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