PXD059643

PXD059643 is an original dataset announced via ProteomeXchange.

Title	Covalent inhibition of Plasmodium falciparum Ubc13 impairs global protein synthesis
Description	The ubiquitin-conjugating enzyme 13 (Ubc13) has an essential function and putative role in artemisinin activity against Plasmodium falciparum. Ubc13 conjugates lysine 63-linked ubiquitin (K63-Ub) to proteins, but the role of this modification in Plasmodium remains largely unknown. Herein, we characterize and deploy NSC697923 to interrogate PfUbc13 function. We demonstrate that NSC697923 covalently targets the PfUbc13 active site residue and exhibits nanomolar inhibitory potency. NSC697923 displays anti-Plasmodium activity against drug-sensitive and drug-resistant asexual strains, gametocytes, and liver stage parasites, and synergizes with the malaria drug dihydroartemisinin. NSC697923 specifically reduces K63-Ub levels in asexual blood stage parasites, and subsequent ubiquitin pull-down assays and proteomic analyses identified putative PfUbc13 substrates. We highlight 37 proteins that overlapped with two previous ubiquitin datasets and were enriched in translation, transcription, and proteasome processes. A cellular puromycin-incorporation study demonstrated reduction of P. falciparum nascent protein synthesis following NSC697923 exposure, supporting a role for PfUbc13 and K63-Ub in mediating parasite protein translation. These findings expand our knowledge of the PfUbc13-dependent processes in these pathogenic parasites and highlight this enzyme as a potential antimalarial drug target.
HostingRepository	PRIDE
AnnounceDate	2025-04-29
AnnouncementXML	Submission_2025-04-29_08:55:46.271.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	grace bertles
SpeciesList	scientific name: Plasmodium falciparum SenT032.09; NCBI TaxID: 1107493;
ModificationList	TMT6plex-126 reporter+balance reagent acylated residue; methylthiolated residue
Instrument	Orbitrap Exploris 480

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-10 08:40:18	ID requested
⏵ 1	2025-04-29 08:55:46	announced

10.1016/J.ISCI.2025.112545;

submitter keyword: Plasmodium

Ubc13

ubiquitin-conjugating enzyme 13

K63-linked ubiquitin

proteomics

artemisinin resistance

Emily Derbyshire
contact affiliation	Chemistry, Duke University, USA
contact email	emily.derbyshire@duke.edu
lab head
grace bertles
contact affiliation	Duke University
contact email	grace.bertles@duke.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD059643
     1. Label: PRIDE project
     2. Name: Covalent inhibition of Plasmodium falciparum Ubc13 impairs global protein synthesis