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PKG

Ca(2+) signals critical for egress and gametogenesis in malaria parasites depend on a multipass membrane protein that interacts with PKG

March 26, 2021 - 16:04 -- Open Access
Author(s): 
Balestra AC, Koussis K, Brochet M, et al.
Reference: 
Sci Adv. 2021 Mar 24;7(13):eabe5396

Calcium signaling regulated by the cGMP-dependent protein kinase (PKG) controls key life cycle transitions in the malaria parasite. However, how calcium is mobilized from intracellular stores in the absence of canonical calcium channels in Plasmodium is unknown. Here, we identify a multipass membrane protein, ICM1, with homology to transporters and calcium channels that is tightly associated with PKG in both asexual blood stages and transmission stages.

Inhibition of Resistance-Refractory P. falciparum Kinase PKG Delivers Prophylactic, Blood Stage, and Transmission-Blocking Antiplasmodial Activity

July 21, 2020 - 12:14 -- Open Access
Author(s): 
Vanaerschot M, Murithi JM, Fidock DA, et al.
Reference: 
Cell Chem Biol. 2020 Jul 16; 27(7):806-816.e8

The search for antimalarial chemotypes with modes of action unrelated to existing drugs has intensified with the recent failure of first-line therapies across Southeast Asia. Here, we show that the trisubstituted imidazole MMV030084 potently inhibits hepatocyte invasion by Plasmodium sporozoites, merozoite egress from asexual blood stage schizonts, and male gamete exflagellation.

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