ATP-Binding Cassette and Solute Carrier Transporters: Understanding Their Mechanisms and Drug Modulation Through Structural and Modeling Approaches DOI Creative Commons
Ahmad Elbahnsi, Bálint Dudás, Isabelle Callebaut

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(12), P. 1602 - 1602

Published: Nov. 27, 2024

The ATP-binding cassette (ABC) and solute carrier (SLC) transporters play pivotal roles in cellular transport mechanisms, influencing a wide range of physiological processes impacting various medical conditions. Recent advancements structural biology computational modeling have provided significant insights into their function regulation. This review provides an overview the current knowledge human ABC SLC transporters, emphasizing functional relationships, contribution approaches to understanding. Current challenges promising future research methodological directions are also discussed.

Language: Английский

Nanomaterials targeting iron homeostasis: a promising strategy for cancer treatment DOI Creative Commons
Bin Li, Dan Mu,

Ziyue Cheng

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2025, Volume and Issue: 13

Published: March 12, 2025

Iron is essential for vital cellular processes, including DNA synthesis, repair, and proliferation, necessitating enhanced iron uptake intracellular accumulation. Tumor cells, in particular, exhibit a pronounced elevation to sustain their continuous migration invasion. This elevated acquisition facilitated predominantly through the upregulation of transferrin receptors, which are closely associated with tumorigenesis tumor progression. Incorporating into drug delivery systems has been shown enhance cytotoxic effects drug-sensitive cancer offering potential method surpass limitations current therapies. Intracellular exists as ferritin heavy chain (FTH), light (FTL), labile pool (LIP). The innovation nanocarriers incorporating chelating agents attracted considerable interest. chelators such Deferoxamine (DFO), Deferasirox (DFX), Dp44mT have demonstrated significant promise treatment by inducing deficiency within cells. review explores recent advancements nanotechnology aimed at targeting metabolism cells discusses applications strategies.

Language: Английский

Citations

0
Structures of ferroportin in complex with its specific inhibitor vamifeport DOI Creative Commons
Elena Farah Lehmann, Márton Liziczai, Katarzyna Drożdżyk

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: March 16, 2023

A central regulatory mechanism of iron homeostasis in humans involves ferroportin (FPN), the sole cellular exporter, and peptide hormone hepcidin, which inhibits Fe

Language: Английский

Citations

9
In vitro reconstitution of transition metal transporters DOI Creative Commons
Elvis Legala Ongey, Anirban Banerjee

Journal of Biological Chemistry, Journal Year: 2024, Volume and Issue: 300(8), P. 107589 - 107589

Published: July 19, 2024

Language: Английский

Citations

2
Iron and Heart Failure: Current Concepts and Emerging Pharmacological Paradigms DOI Open Access
Maria Rosaria Pascale, Maria Beatrice Rondinelli,

Flora Ascione

et al.

World Journal of Cardiovascular Diseases, Journal Year: 2024, Volume and Issue: 14(04), P. 195 - 216

Published: Jan. 1, 2024

Background: Emerging evidence has recognized that anemia and iron deficiency are recurrent comorbidities in chronic heart failure (HF) several trials have established administration improves myocardial asset clinical scenario HF. Purpose: Recent acquisitions suggest represents a concrete bias the pathogenetic mechanism of HF, so we investigated putative role hepcidin/ferroportin axis cardiovascular setting to advocate novel pharmacological approaches. Methods: Here, after an excursus on metabolism, first reviewed ongoing studies targeted compounds. Then, summarize large interventional conducted patient suffering from HF which tested effects drugging regard QoL, hospitalizations death. Results: Novel compounds such as hepcidin agonist (PTG 300), synthetic human (LJPC-401) anti FPN (Vamifeport) overloaded patients, while blocker (PRS-080) is under investigation anemic patients. Noteworthy, insights could arise results Phase IV study regarding modification pathway cohort patients (n = 1992) by sodium glucose cotransporter 2 inhibitors. To date, highlight beneficial effect latest evidences consider level biomarker cardiac injury atherosclerosis. Conclusions: We data will therapies for diagnosis, prognosis therapy transferable selected failed

Language: Английский

Citations

1
The role of ferroptosis in acute kidney injury: mechanisms and potential therapeutic targets DOI
Yanxin Yu, Lei Zhang, Die Zhang

et al.

Molecular and Cellular Biochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: June 28, 2024

Language: Английский

Citations

1
Structural insights into ferroportin mediated iron transport DOI
Mika Jormakka

Biochemical Society Transactions, Journal Year: 2023, Volume and Issue: 51(6), P. 2143 - 2152

Published: Dec. 20, 2023

Iron is a vital trace element for almost all organisms, and maintaining iron homeostasis critical human health. In mammals, the only known gatekeeper between intestinally absorbed circulatory blood plasma membrane transporter ferroportin (Fpn). As such, dysfunction of Fpn or its regulation key driver iron-related pathophysiology. This review focuses on discussing recent insights from high-resolution structural studies protein family. While these have unveiled crucial details architecture, associated functional also at times provided conflicting data provoking more questions than answers. Here, we summarize findings illuminate important remaining contradictions.

Language: Английский

Citations

2
Genetic Incorporation of Dansylalanine in Human Ferroportin to Probe the Alternating Access Mechanism of Iron Transport DOI Open Access
Matteo Amadei,

Antonella Niro,

Maria Rosaria Fullone

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(15), P. 11919 - 11919

Published: July 25, 2023

Ferroportin (Fpn), a member of the major facilitator superfamily (MFS) transporters, is only known iron exporter found in mammals and plays crucial role regulating cellular systemic levels. MFSs take on different conformational states during transport cycle: inward open, occluded, outward open. However, precise molecular mechanism translocation by Fpn remains unclear, with conflicting data proposing models. In this work, amber codon suppression was employed to introduce dansylalanine (DA), an environment-sensitive fluorescent amino acid, into specific positions human (V46, Y54, V161, Y331) predicted undergo changes metal translocation. The results obtained indicate that mutants exhibit distinct fluorescence spectra depending position fluorophore within structure, suggesting local environments can be probed. Cobalt titration experiments revealed quenching blue-shifts λmax Y54DA, V161DA, Y331DA, while V46DA exhibited increased blue-shift λmax. These observations suggest metal-induced transitions, interpreted terms shifts from outward-open occluded conformation. Our study highlights potential genetically incorporating DA Fpn, enabling investigation using spectroscopy. This approach holds great promise for alternating access advancing our understanding basis transport.

Language: Английский

Citations

1
Recent advances in expression screening and sample evaluation for structural studies of membrane proteins DOI Creative Commons
Yichen Huang, Ziyi Zhang, Motoyuki Hattori

et al.

Journal of Molecular Biology, Journal Year: 2024, Volume and Issue: 436(22), P. 168809 - 168809

Published: Oct. 2, 2024

Language: Английский

Citations

0
ATP-Binding Cassette and Solute Carrier Transporters: Understanding Their Mechanisms and Drug Modulation Through Structural and Modeling Approaches DOI Creative Commons
Ahmad Elbahnsi, Bálint Dudás, Isabelle Callebaut

et al.

Pharmaceuticals, Journal Year: 2024, Volume and Issue: 17(12), P. 1602 - 1602

Published: Nov. 27, 2024

The ATP-binding cassette (ABC) and solute carrier (SLC) transporters play pivotal roles in cellular transport mechanisms, influencing a wide range of physiological processes impacting various medical conditions. Recent advancements structural biology computational modeling have provided significant insights into their function regulation. This review provides an overview the current knowledge human ABC SLC transporters, emphasizing functional relationships, contribution approaches to understanding. Current challenges promising future research methodological directions are also discussed.

Language: Английский

Citations

0