ArticleeLife2019
Mechanistic basis of the inhibition of SLC11/NRAMP-mediated metal ion transport by bis-isothiourea substituted compounds.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Fluorescence-Based Ion Transport Assays Using Proteoliposomes.Bio-protocol · 2026Article
- Structural basis for metal ion transport by the human SLC11 proteins DMT1 and NRAMP1.Nature communications · 2025Article
- In vitro reconstitution of transition metal transporters.The Journal of biological chemistry · 2024Review
- Genome-Wide Identification and Expression Analysis of SlNRAMP Genes in Tomato under Nutrient Deficiency and Cadmium Stress during Arbuscular Mycorrhizal Symbiosis.International journal of molecular sciences · 2024Article
- Managing Iron Overload: A Gut Check.The Journal of pharmacology and experimental therapeutics · 2023Article
- High-resolution structures with bound MneLife · 2023Article
- The Allelic Variant A391T of Metal Ion Transporter ZIP8 (SLC39A8) Leads to Hypotension and Enhanced Insulin Resistance.Frontiers in physiology · 2022Article
- Chelators for Treatment of Iron and Copper Overload: Shift from Low-Molecular-Weight Compounds to Polymers.Polymers · 2021Review
- Inhibitors of Human Divalent Metal Transporters DMT1 (SLC11A2) and ZIP8 (SLC39A8) from a GDB-17 Fragment Library.ChemMedChem · 2021Article
- Molecular Mechanism of Nramp-Family Transition Metal Transport.Journal of molecular biology · 2021Review
- Ironing out mechanisms of iron homeostasis and disorders of iron deficiency.The Journal of clinical investigation · 2021Review
- Article
- Cellular Dynamics of Transition Metal Exchange on Proteins: A Challenge but a Bonanza for Coordination Chemistry.Biomolecules · 2020Review
- Pyrazolyl-pyrimidones inhibit the function of human solute carrier protein SLC11A2 (hDMT1) by metal chelation.RSC medicinal chemistry · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
In humans, the divalent metal ion transporter-1 (DMT1) mediates the transport of ferrous iron across the apical membrane of enterocytes. Hence, its inhibition could be beneficial for the treatment of iron overload disorders. Here we characterize the interaction of aromatic bis-isothiourea-substituted compounds with human DMT1 and its prokaryotic homologue EcoDMT. Both transporters are inhibited by a common competitive mechanism with potencies in the low micromolar range. The crystal structure of EcoDMT in complex with a brominated derivative defines the binding of the inhibitor to an extracellular pocket of the transporter in direct contact with residues of the metal ion coordination site, thereby interfering with substrate loading and locking the transporter in its outward-facing state. Mutagenesis and structure-activity relationships further support the observed interaction mode and reveal species-dependent differences between pro- and eukaryotic transporters. Together, our data provide the first detailed mechanistic insight into the pharmacology of SLC11/NRAMP transporters.
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