Among the malaria-causing parasites, the deadliest isPlasmodium falciparum, which accounts for the majority of the fatalities. As the infection progresses inside erythrocytes, major cellular and metabolic changes take place. For its own growth, the parasite relies on the accumulation of phospholipids, which are essential for membrane synthesis. Within the Kennedy pathway, theP. falciparumcholine kinase (PfChoK) has a central role in the biosynthesis of phosphatidylcholine and its selective inhibition leads to the parasite arrest and eradication. Here, we report the crystal structure of the apo and the ADP-bound form of choline kinase fromPlasmodium falciparumat 2.0 and 2.2 angstrom resolution, respectively. These new structural data will facilitate the implementation of effective structure-based drug development strategies against PfChoK in the fight against malaria.
Archimede Torretta, Luisa Carlota Lopez-Cara, Emilio Parisini (2020). Crystal Structure of the Apo and the ADP-Bound Form of Choline Kinase from Plasmodium falciparum. CRYSTALS, 10(7), 1-13 [10.3390/cryst10070613].
Crystal Structure of the Apo and the ADP-Bound Form of Choline Kinase from Plasmodium falciparum
Archimede Torretta;Emilio Parisini
2020
Abstract
Among the malaria-causing parasites, the deadliest isPlasmodium falciparum, which accounts for the majority of the fatalities. As the infection progresses inside erythrocytes, major cellular and metabolic changes take place. For its own growth, the parasite relies on the accumulation of phospholipids, which are essential for membrane synthesis. Within the Kennedy pathway, theP. falciparumcholine kinase (PfChoK) has a central role in the biosynthesis of phosphatidylcholine and its selective inhibition leads to the parasite arrest and eradication. Here, we report the crystal structure of the apo and the ADP-bound form of choline kinase fromPlasmodium falciparumat 2.0 and 2.2 angstrom resolution, respectively. These new structural data will facilitate the implementation of effective structure-based drug development strategies against PfChoK in the fight against malaria.File | Dimensione | Formato | |
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