ArticleAntimicrobial agents and chemotherapy2014
Sulfur mobilization for Fe-S cluster assembly by the essential SUF pathway in the Plasmodium falciparum apicoplast and its inhibition.
Article in Antimicrobial agents and chemotherapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 56 citations in OpenAlex.
- A bacterial-type cardiolipin synthase in Plasmodium spp. supports mitochondrial respiration and is important for liver stage maturation.PLoS pathogens · 2026Article
- Coordination of the Fe-S cluster biogenesis network by the sRNA RyhB inRNA biology · 2025Article
- Discovery of an Aziridine-Based Inhibitor That Targets Cysteine Desulfurase Type II SufS via High-Throughput X‑ray Crystallography.ACS medicinal chemistry letters · 2025Article
- Identification of a Selective Inhibitor of Human NFS1, a Cysteine Desulfurase Involved in Fe-S Cluster Assembly, via Structure-Based Virtual Screening.International journal of molecular sciences · 2025Article
- Development of a Spectrophotometric Assay for the Cysteine Desulfurase fromAntibiotics (Basel, Switzerland) · 2025Article
- tRNA modifying enzymes MnmE and MnmG are essential forbioRxiv : the preprint server for biology · 2025Article
- Malaria parasites require a divergent heme oxygenase for apicoplast gene expression and biogenesis.eLife · 2024Article
- Malaria parasites require a divergent heme oxygenase for apicoplast gene expression and biogenesis.bioRxiv : the preprint server for biology · 2024Article
- ATM1, an essential conserved transporter in Apicomplexa, bridges mitochondrial and cytosolic [Fe-S] biogenesis.PLoS pathogens · 2024Article
- Apicoplast-Resident Processes: Exploiting the Chink in the Armour ofAdvances in pharmacological and pharmaceutical sciences · 2024Review
- The interdependence of isoprenoid synthesis and apicoplast biogenesis in malaria parasites.PLoS pathogens · 2023Article
- TheeLife · 2023Article
- The ferredoxin redox system - an essential electron distributing hub in the apicoplast of Apicomplexa.Trends in parasitology · 2022Review
- Review
- Differential contribution of two organelles of endosymbiotic origin to iron-sulfur cluster synthesis and overall fitness in Toxoplasma.PLoS pathogens · 2021Article
- The Multifaceted Bacterial Cysteine Desulfurases: From Metabolism to Pathogenesis.Antioxidants (Basel, Switzerland) · 2021Review
- Lipoic Acid Metabolism as a Potential Chemotherapeutic Target AgainstFrontiers in chemistry · 2021Review
- Fe-S cluster biogenesis by the bacterial Suf pathway.Biochimica et biophysica acta. Molecular cell research · 2020Review
- Repurposing Drugs to Fight Hepatic Malaria Parasites.Molecules (Basel, Switzerland) · 2020Review
- Discovery of a Natural Product That Binds to theMolecules (Basel, Switzerland) · 2020Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The plastid of the malaria parasite, the apicoplast, is essential for parasite survival. It houses several pathways of bacterial origin that are considered attractive sites for drug intervention. Among these is the sulfur mobilization (SUF) pathway of Fe-S cluster biogenesis. Although the SUF pathway is essential for apicoplast maintenance and parasite survival, there has been limited biochemical investigation of its components and inhibitors of Plasmodium SUFs have not been identified. We report the characterization of two proteins, Plasmodium falciparum SufS (PfSufS) and PfSufE, that mobilize sulfur in the first step of Fe-S cluster assembly and confirm their exclusive localization to the apicoplast. The cysteine desulfurase activity of PfSufS is greatly enhanced by PfSufE, and the PfSufS-PfSufE complex is detected in vivo. Structural modeling of the complex reveals proximal positioning of conserved cysteine residues of the two proteins that would allow sulfide transfer from the PLP (pyridoxal phosphate) cofactor-bound active site of PfSufS. Sulfide release from the l-cysteine substrate catalyzed by PfSufS is inhibited by the PLP inhibitor d-cycloserine, which forms an adduct with PfSufS-bound PLP. d-Cycloserine is also inimical to parasite growth, with a 50% inhibitory concentration close to that reported for Mycobacterium tuberculosis, against which the drug is in clinical use. Our results establish the function of two proteins that mediate sulfur mobilization, the first step in the apicoplast SUF pathway, and provide a rationale for drug design based on inactivation of the PLP cofactor of PfSufS.
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