Fig. 4.

Inhibition of P. falciparum SUB1 maturation and egress by selected compounds indicates that they target Plm X. (A) Synchronous cultures of immature intracellular parasites were treated for ∼8 h with compounds (S,R)-2a or (S,R)-4b,c (10 nM), or vehicle only (DMSO, 1% v/v), or the cGMP-dependent protein kinase inhibitor (4-[7-[(dimethylamino)methyl]-2-(4-fluorphenyl)imidazo[1,2-α]pyridine-3-yl]pyrimidin-2-amine (compound 2; C2, 2 μM) which inhibits egress but not SUB1 maturation. Extracts of the parasites were then analyzed by Western blot, probing with an antibody to SUB1. The positions of migration of the SUB1 p54 and p47 forms (green arrow) are indicated. The schematic below indicates the mode by which Plm X converts SUB1 p54 to the terminal p47 form. (B) Parasites treated for ∼ 24 h as in (A) were transferred to fresh medium containing the various compounds and allowed to undergo egress for 4 h before the culture supernatants were analysed by Western blot, probing with antibodies to the parasite protein SERA5. The positions of migration of the SERA5 precursor, a processing intermediate and the terminal P50 form (green arrow) are indicated. The schematic below indicates the mode by which SUB1 converts the SERA5 precursor to the P50 form. (For interpretation of the references to color in this figure legend, the reader is referred to the Web version of this article.)