PXD010264 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Comparison of the proteome-wide alkylation signatures of antimalarial peroxides: ozonides vs. artemisinin |
Description | Antimalarial peroxides such as the phytochemical artemisinin or the synthetic artefenomel are activated by reductive cleavage of the peroxide bond. This happens inside the malaria parasite, presumably in the food vacuole with ferrous heme as the electron donor. The generated carbon-centered radicals will then alkylate heme itself as well as proteins. Here we determine the proteinaceous alkylation signatures of artemisinin and synthetic ozonides by chemical proteomics in Plasmodium falciparum, using alkyne probes to identify target proteins by click chemistry, affinity purification and mass spectrometry-based proteomics. Two forms of negative controls were included: the non-clickable parent peroxides, as well as clickable but non-peroxidic derivatives. Using this approach and stringent purification procedures, we identified 25 P. falciparum proteins that were alkylated by the antimalarial peroxides in a peroxide-dependent manner and at physiological concentration (100 ng/ml); higher exposure (1000 ng/ml) added another 19 proteins to the target lists. Gene ontology term enrichment was performed to analyze the differences between the alkylation signatures of ozonide- and artemisinin-based alkyne probes. This identified overrepresentation of unfolded protein binding, in particular the chaperonin-containing T-complex (TRiC), as the main difference between ozonides and artemisinin, the very mechanism that is involved in artemisinin resistance. Thus differences in the alkylation signatures may account for the lack of cross-resistance between artemisinin and artefenomel. |
HostingRepository | PRIDE |
AnnounceDate | 2022-02-24 |
AnnouncementXML | Submission_2022-02-24_04:23:05.950.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD010264 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Alexander Schmidt |
SpeciesList | scientific name: Plasmodium falciparum NF135/5.C10; NCBI TaxID: 1036726; |
ModificationList | Oxidation; Acetyl; Carbamidomethyl |
Instrument | LTQ FT |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2018-06-28 23:11:40 | ID requested | |
⏵ 1 | 2022-02-24 04:23:06 | announced | |
Publication List
Jourdan J, Walz A, Matile H, Schmidt A, Wu J, Wang X, Dong Y, Vennerstrom JL, Schmidt RS, Wittlin S, M, รค, ser P, Stochastic Protein Alkylation by Antimalarial Peroxides. ACS Infect Dis, 5(12):2067-2075(2019) [pubmed] |
Keyword List
curator keyword: Biomedical |
submitter keyword: Malaria, peroxides, label-free quantification |
Contact List
Alexander Schmidt |
contact affiliation | Proteomics Care Facilty, Biozentrum, University of Basel, Switzerland |
contact email | alex.schmidt@unibas.ch |
lab head | |
Alexander Schmidt |
contact affiliation | Proteomics Core Facility |
contact email | alex.schmidt@unibas.ch |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD010264
- Label: PRIDE project
- Name: Comparison of the proteome-wide alkylation signatures of antimalarial peroxides: ozonides vs. artemisinin