ArticlePLoS pathogens2019
Nedd8 hydrolysis by UCH proteases in Plasmodium parasites.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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Who cites it
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 30 citations in OpenAlex.
- Unsupervised Human Activity Recognition Using the Clustering Approach: A Review.Sensors (Basel, Switzerland) · 2020Pooled it
- Activity-based protein profiling reveals both canonical and novel ubiquitin pathway enzymes in Plasmodium.PLoS pathogens · 2025Article
- Proteasome associated function of UCH37 is evolutionarily conserved in Plasmodium parasites.Scientific reports · 2024Article
- A Modular Biosensor Design for Quantitative Measurement of Free Nedd8.ACS sensors · 2024Article
- Post-Translational Modifications of Proteins of Malaria Parasites during the Life Cycle.International journal of molecular sciences · 2024Review
- Article
- Plasmodium falciparum contains functional SCF and CRL4 ubiquitin E3 ligases, and CRL4 is critical for cell division and membrane integrity.PLoS pathogens · 2024Article
- Identification of covalent fragment inhibitors for Plasmodium falciparum UCHL3 with anti-malarial efficacy.Bioorganic & medicinal chemistry letters · 2023Article
- The Skp1-Cullin1-FBXO1 complex is a pleiotropic regulator required for the formation of gametes and motile forms in Plasmodium berghei.Nature communications · 2023Article
- Using Graph-Based Signatures to Guide Rational Antibody Engineering.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Reaction hijacking of tyrosine tRNA synthetase as a new whole-of-life-cycle antimalarial strategy.Science (New York, N.Y.) · 2022Article
- Article
- The emerging role of Deubiquitinases (DUBs) in parasites: A foresight review.Frontiers in cellular and infection microbiology · 2022Review
- PfMFR3: A Multidrug-Resistant Modulator inACS infectious diseases · 2021Article
- DynaMut2: Assessing changes in stability and flexibility upon single and multiple point missense mutations.Protein science : a publication of the Protein Society · 2021Article
- Characterization of Plasmodium falciparum NEDD8 and identification of cullins as its substrates.Scientific reports · 2020Article
- Ubiquitin-Like Modifiers: Emerging Regulators of Protozoan Parasites.Biomolecules · 2020Review
- COP9 signalosome is an essential and druggable parasite target that regulates protein degradation.PLoS pathogens · 2020Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Plasmodium parasites are the causative agents of malaria, a disease with wide public health repercussions. Increasing drug resistance and the absence of a vaccine make finding new chemotherapeutic strategies imperative. Components of the ubiquitin and ubiquitin-like pathways have garnered increased attention as novel targets given their necessity to parasite survival. Understanding how these pathways are regulated in Plasmodium and identifying differences to the host is paramount to selectively interfering with parasites. Here, we focus on Nedd8 modification in Plasmodium falciparum, given its central role to cell division and DNA repair, processes critical to Plasmodium parasites given their unusual cell cycle and requirement for refined repair mechanisms. By applying a functional chemical approach, we show that deNeddylation is controlled by a different set of enzymes in the parasite versus the human host. We elucidate the molecular determinants of the unusual dual ubiquitin/Nedd8 recognition by the essential PfUCH37 enzyme and, through parasite transgenics and drug assays, determine that only its ubiquitin activity is critical to parasite survival. Our experiments reveal interesting evolutionary differences in how neddylation is controlled in higher versus lower eukaryotes, and highlight the Nedd8 pathway as worthy of further exploration for therapeutic targeting in antimalarial drug design.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.