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Adv."],"published-print":{"date-parts":[[2026,3,13]]},"abstract":"<jats:p>\n                    Coenzyme A (CoA) is essential for the intraerythrocytic stage of\n                    <jats:italic toggle=\"yes\">Plasmodium falciparum<\/jats:italic>\n                    . Phosphopantothenoylcysteine synthetase (PPCS) catalyzes the second of five steps of the CoA biosynthesis pathway. Most apicomplexan parasites express one PPCS, whereas two PPCSs are expressed in\n                    <jats:italic toggle=\"yes\">P. falciparum<\/jats:italic>\n                    . Here, we demonstrate that the two\n                    <jats:italic toggle=\"yes\">P. falciparum<\/jats:italic>\n                    PPCSs (\n                    <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                    PPCSs) associate into a single, functional PPCS heteromeric complex that, unlike any other eukaryotic PPCS reported to date, is unable to use adenosine 5\u2032-triphosphate. We identify a prokaryote-like helical component of\n                    <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                    PPCS as important for the nucleotide specificity and potentially holding the key for its stringency for cytidine 5\u2032-triphosphate. Moreover, we show that the complex is the target of multiple antiplasmodial pantothenate analogs and interacts with other analogs that target different steps in CoA biosynthesis\/utilization. Our study provides opportunities for designing inhibitors that exploit the unique features of the\n                    <jats:italic toggle=\"yes\">Pf<\/jats:italic>\n                    PPCS complex while, at the same time, avoiding the human counterpart, paving the way for additional therapies to combat malaria.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.adx5265","type":"journal-article","created":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T17:58:33Z","timestamp":1773424713000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["The\n                    <i>Plasmodium falciparum<\/i>\n                    PPCS is a unique heteromeric complex with prokaryote-like activity and is a target of pantothenate 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