ArticleNature communications2014
A sugar phosphatase regulates the methylerythritol phosphate (MEP) pathway in malaria parasites.
Article in Nature communications, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed.
- Article
- The mevalonate and methylerythritol phosphate pathways as therapeutic targets in protozoan parasites: from moonlighting enzymes to metabolic plasticity.Cell communication and signaling : CCS · 2026Review
- Advancements in CRISPR-Cas Systems for Genome Editing towards Eradication of Human Microbial Pathogens.Molecular biotechnology · 2026Review
- Essential role for PfHSP40 in asexual replication and thermotolerance of malaria parasites.PLoS pathogens · 2025Article
- Host-Derived Geranylgeraniol Shields Intraerythrocytic Stages of Malaria Parasites from Fosmidomycin.Research square · 2025Article
- Prodrug activation in malaria parasites mediated by an imported erythrocyte esterase, acylpeptide hydrolase (APEH).Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- Prodrug activation in malaria parasites mediated by an imported erythrocyte esterase, acylpeptide hydrolase (APEH).bioRxiv : the preprint server for biology · 2024Article
- A picomolar inhibitor of theAntimicrobial agents and chemotherapy · 2024Article
- Inhibition of DXR in the MEP pathway with lipophilicRSC medicinal chemistry · 2024Article
- In silico prediction and in vitro assessment of novel heterocyclics with antimalarial activity.Parasitology research · 2023Article
- MEPicides: α,β-unsaturated FosmidomycinACS infectious diseases · 2023Article
- New insights into apicoplast metabolism in blood-stage malaria parasites.Current opinion in microbiology · 2023Review
- GAPDH mediates drug resistance and metabolism in Plasmodium falciparum malaria parasites.PLoS pathogens · 2022Article
- Comparative Analysis of the Metabolome and Transcriptome between the Green and Yellow-Green Regions of Variegated Leaves in a Mutant Variety of the Tree SpeciesInternational journal of molecular sciences · 2022Article
- Enzymatic and structural characterization of HAD5, an essential phosphomannomutase of malaria-causing parasites.The Journal of biological chemistry · 2022Article
- Engineering ofFrontiers in bioengineering and biotechnology · 2022Article
- The apicoplast link to fever-survival and artemisinin-resistance in the malaria parasite.Nature communications · 2021Article
- Protein Prenylation and Hsp40 in Thermotolerance of Plasmodium falciparum Malaria Parasites.mBio · 2021Article
- Non-canonical metabolic pathways in the malaria parasite detected by isotope-tracing metabolomics.Molecular systems biology · 2021Article
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7 authors.
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Abstract
Isoprenoid biosynthesis through the methylerythritol phosphate (MEP) pathway generates commercially important products and is a target for antimicrobial drug development. MEP pathway regulation is poorly understood in microorganisms. Here we employ a forward genetics approach to understand MEP pathway regulation in the malaria parasite, Plasmodium falciparum. The antimalarial fosmidomycin inhibits the MEP pathway enzyme deoxyxylulose 5-phosphate reductoisomerase (DXR). Fosmidomycin-resistant P. falciparum are enriched for changes in the PF3D7_1033400 locus (hereafter referred to as PfHAD1), encoding a homologue of haloacid dehalogenase (HAD)-like sugar phosphatases. We describe the structural basis for loss-of-function PfHAD1 alleles and find that PfHAD1 dephosphorylates a variety of sugar phosphates, including glycolytic intermediates. Loss of PfHAD1 is required for fosmidomycin resistance. Parasites lacking PfHAD1 have increased MEP pathway metabolites, particularly the DXR substrate, deoxyxylulose 5-phosphate. PfHAD1 therefore controls substrate availability to the MEP pathway. Because PfHAD1 has homologues in plants and bacteria, other HAD proteins may be MEP pathway regulators.
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