Protein Acylation: New Potential Targets for Intervention against the Apicomplexa

Santos, Joana; Hedberg, Christian; Soldati‐Favre, Dominique

doi:10.1002/9783527633883.ch18

Cited by 1 publication

(1 citation statement)

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“…This protein was annotated as a putative phospholipase/carboxylesterase ( Supplementary Tables 1 and 2 ) and bioinformatic analysis using BLAST identified it as the likely orthologue of human APT1 (33% identity), a thioesterase responsible for the removal of palmitoyl groups from protein substrates 19 . Although there was no published functional data for this gene product, the locus was previously aligned with rat APT1 and named palmitoyl-protein thioesterase-1 (TgPPT1) 20 .…”

Section: Resultsmentioning

confidence: 99%

Small-molecule inhibition of a depalmitoylase enhances Toxoplasma host-cell invasion

et al. 2013

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While there have been numerous advances in our understanding of how apicomplexan parasites such as Toxoplasma gondii enter host cells, many of the signaling pathways and enzymes involved in the organization of invasion mediators remain poorly defined. We recently performed a forward chemical genetic screen in T. gondii and identified compounds that markedly enhanced infectivity. Although molecular dissection of invasion has benefited from the use of small-molecule inhibitors, the mechanisms underlying induction of invasion by small-molecule enhancers have never been described. Here we identify the Toxoplasma orthologue of human APT1, palmitoyl protein thioesterase-1 (TgPPT1), as the target of one class of small molecule enhancers. Inhibition of this uncharacterized thioesterase triggered secretion of invasion-associated organelles, increased motility and enhanced the invasive capacity of tachyzoites. We demonstrate that TgPPT1 is a bona fide depalmitoylase, thereby establishing an important role for dynamic and reversible palmitoylation in host-cell invasion by T. gondii.

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Section: Resultsmentioning

confidence: 99%