RT Journal Article SR Electronic T1 Purification of functional Plasmodium falciparum tubulin allows for the identification of parasite-specific microtubule inhibitors JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.05.25.445550 DO 10.1101/2021.05.25.445550 A1 William Graham Hirst A1 Dominik Fachet A1 Benno Kuropka A1 Christoph Weise A1 Kevin Saliba A1 Simone Reber YR 2021 UL http://biorxiv.org/content/early/2021/05/25/2021.05.25.445550.abstract AB Cytoskeletal proteins are essential for parasite proliferation, growth, and transmission, and therefore represent promising drug targets. While αβ-tubulin, the molecular building block of microtubules, is an established drug target in a variety of cancers, we still lack substantial knowledge of the biochemistry of parasite tubulins, which would allow us to exploit the structural divergence between parasite and human tubulins. Indeed, mechanistic insights have been limited by the lack of purified, functional parasite tubulin. In this study, we isolated Plasmodium falciparum tubulin that is assembly-competent and shows specific microtubule dynamics in vitro. We further present mechanistic evidence that two compounds selectively interact with parasite over host microtubules and inhibit Plasmodium microtubule polymerization at substoichiometric compound concentrations. The ability of compounds to selectively disrupt protozoan microtubule growth without affecting human microtubules provides the exciting possibility for the targeted development of novel antimalarials.Competing Interest StatementThe authors have declared no competing interest.