Global proteomic analysis of prenylated proteins in Plasmodium falciparum using an alkyne-modified isoprenoid analogue

Kiall Francis G Suazo, Chad Schaber, Charuta C. Palsuledesai, Audrey R. Odom John, Mark D Distefano

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Severe malaria due to Plasmodium falciparum infection remains a serious threat to health worldwide and new therapeutic targets are highly desirable. Small molecule inhibitors of prenyl transferases, enzymes that catalyze the post-translational isoprenyl modifications of proteins, exhibit potent antimalarial activity. The antimalarial actions of prenyltransferase inhibitors indicate that protein prenylation is required for malaria parasite development. In this study, we used a chemical biology strategy to experimentally characterize the entire complement of prenylated proteins in the human malaria parasite. In contrast to the expansive mammalian and fungal prenylomes, we find that P. falciparum possesses a restricted set of prenylated proteins. The prenylome of P. falciparum is dominated by Rab GTPases, in addition to a small number of prenylated proteins that also appear to function primarily in membrane trafficking. Overall, we found robust experimental evidence for a total of only thirteen prenylated proteins in P. falciparum, with suggestive evidence for an additional two probable prenyltransferase substrates. Our work contributes to an increasingly complete picture of essential, post-translational hydrophobic modifications in blood-stage P. falciparum.

Original languageEnglish (US)
Article number38615
JournalScientific reports
Volume6
DOIs
StatePublished - Dec 7 2016

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Alkynes
Terpenes
Plasmodium falciparum
Proteomics
Malaria
Dimethylallyltranstransferase
Antimalarials
Post Translational Protein Processing
Proteins
Parasites
Protein Prenylation
rab GTP-Binding Proteins
Transferases
Complement System Proteins
Membranes
Enzymes

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Global proteomic analysis of prenylated proteins in Plasmodium falciparum using an alkyne-modified isoprenoid analogue. / Suazo, Kiall Francis G; Schaber, Chad; Palsuledesai, Charuta C.; Odom John, Audrey R.; Distefano, Mark D.

In: Scientific reports, Vol. 6, 38615, 07.12.2016.

Research output: Contribution to journalArticle

Suazo, Kiall Francis G ; Schaber, Chad ; Palsuledesai, Charuta C. ; Odom John, Audrey R. ; Distefano, Mark D. / Global proteomic analysis of prenylated proteins in Plasmodium falciparum using an alkyne-modified isoprenoid analogue. In: Scientific reports. 2016 ; Vol. 6.
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