<<< Full experiment listing

PXD036092

PXD036092 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleIsoprenoid alcohols utilization by malaria parasites
DescriptionPlasmodium falciparum is the etiological agent of human malaria, one of the most widespread diseases in tropical and subtropical world regions. One of the biggest problems in controlling the disease is the emergence of drug resistance, which leads to the need to discover new antimalarial compounds. One of the most promissory drugs purposed is fosmidomycin, an inhibitor of the biosynthesis of isoprene units by the methylerythritol 4-phosphate (MEP) pathway which in some cases failed in clinic studies. Once formed, isoprene units are condensed to form longer structures such as farnesyl and geranylgeranyl pyrophosphate (GGPP), which are necessary for heme O and A formation, ubiquinone, and dolichyl phosphate biosynthesis as well as for protein isoprenylation. Even though the natural substrates of polyprenyl transferases and syntheses are polyprenyl pyrophosphates, it was already demonstrated that isoprenoid alcohols (polyprenols) such as farnesol (FOH) and geranylgeraniol (GGOH) can rescue parasites from fosmidomycin. This study better investigated how this rescue phenomenon occurs by performing drug-rescue assays. By this, it was observed that phytol (POH), a 20-carbon plant isoprenoid, rescues parasites from the fosmidomycin effect, similarly to FOH or GGOH. Contrarily, neither dolichols nor nonaprenol rescue parasites from fosmidomycin. Considering this, here we characterized the transport of FOH, GGOH, and POH. Once incorporated, it was observed that these substances are phosphorylated, condensed into longer isoprenoid alcohols, and incorporated into proteins and dolichyl phosphates. Through proteomic and radiolabelling approaches, it was found that prenylated proteins are naturally attached to several isoprenoids including GGOH, dolichol, and POH if exogenously added. Furthermore, results suggest the presence of at least two promiscuous protein prenyltransferases in the parasite: one enzyme which can use FPP among other unidentified substrates and another enzyme that can use GGOH, POH, and dolichols among other substrates not identified here. Thus, was obtained further evidence for dolichols and other isoprenoid products attached to proteins. This study helps better understand apicoplast-targeting antimalarials mechanism of action as well as novel posttranslational modifications of proteins.
HostingRepositoryPRIDE
AnnounceDate2023-11-14
AnnouncementXMLSubmission_2023-11-14_08:58:31.667.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterVeronica Santiago
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentLTQ Orbitrap Velos
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-08-16 13:30:30ID requested
12022-11-28 07:58:23announced
22023-11-14 08:58:32announced2023-11-14: Updated project metadata.
Publication List
Dataset with its publication pending
Keyword List
submitter keyword: geranylgeraniol, malaria, dolichols, isoprenoid biosynthesis, phytol, farnesol, fosmidomycin,isoprenoid alcohols, protein dolichylation, Plasmodium falciparum, protein prenylation
Contact List
Alejandro Miguel Katzin
contact affiliationDepartment of Parasitology, Institute of Biomedical Sciences of the University of São Paulo, Av. Lineu Prestes 1374, CEP 05508-000, São Paulo, SP, Brazil. Telephone: +55 11 3091-7330 Fax: 5511 3091-7417. E-mail address: amkatzin@icb.usp.br (A. M. Katzin)
contact emailamkatzin@icb.usp.br
lab head
Veronica Santiago
contact affiliationUniversity of Southampton
contact emailveronicafeijoli@usp.br
dataset submitter
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2022/11/PXD036092
PRIDE project URI
Repository Record List
[ + ]