ArticleJournal of the American Chemical Society2016
Unusual Synergism of Transferrin and Citrate in the Regulation of Ti(IV) Speciation, Transport, and Toxicity.
Article in Journal of the American Chemical Society, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 62 citations in OpenAlex.
- Reinforcing Protein Biochemistry: A Two-Week Experiment Studying Iron(III) Binding by the Transferrin Protein through Stoichiometric Determination, Stability Analysis, and Visualization of the Binding Site.Journal of chemical education · 2024Article
- Cisplatin Binding to Human Serum Transferrin: A Crystallographic Study.Inorganic chemistry · 2023Article
- Ion release and local effects of titanium metal particles from dental implants: An experimental study in rats.Journal of periodontology · 2023Article
- Quantifying In Situ Structural Stabilities of Human Blood Plasma Proteins Using a Novel Iodination Protein Stability Assay.Journal of proteome research · 2022Article
- Controversial Role of Transferrin in the Transport of Ruthenium Anticancer Drugs.Biomolecules · 2022Article
- Root Breeding in the Post-Genomics Era: From Concept to Practice in Apple.Plants (Basel, Switzerland) · 2022Review
- Advantageous Reactivity of Unstable Metal Complexes: Potential Applications of Metal-Based Anticancer Drugs for Intratumoral Injections.Pharmaceutics · 2022Review
- Exploring Titanium(IV) Complexes as Potential Antimicrobial Compounds.Antibiotics (Basel, Switzerland) · 2022Article
- Urea Gel Electrophoresis in Studies of Conformational Changes of Transferrin on Binding and Transport of Non-Ferric Metal Ions.Gels (Basel, Switzerland) · 2021Article
- The impacts of different anticoagulants and long-term frozen storage on multiple metal concentrations in peripheral blood: a comparative study.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2021Article
- Article
- Using X-ray Diffraction Techniques for Biomimetic Drug Development, Formulation, and Polymorphic Characterization.Biomimetics (Basel, Switzerland) · 2020Review
- Exploring Serum Transferrin Regulation of Nonferric Metal Therapeutic Function and Toxicity.Inorganics · 2020Article
- Toxic and Physiological Metal Uptake and Release by Human Serum Transferrin.Biophysical journal · 2020Article
- Molecular dynamics simulations of plutonium binding and its decorporation from the binding-cleft of human serum transferrin.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2020Article
- Evaluating Ligand Modifications of the Titanocene and Auranofin Moieties for the Development of More Potent Anticancer Drugs.Inorganics · 2020Article
- Fueling a Hot Debate on the Application of TiOMaterials (Basel, Switzerland) · 2019Review
- Exploring titanium(IV) chemical proximity to iron(III) to elucidate a function for Ti(IV) in the human body.Coordination chemistry reviews · 2018Article
- The role of citrate, lactate and transferrin in determining titanium release from surgical devices into human serum.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2018Article
- Are cucurbiturils better drug carriers for bent metallocenes? Insights from theory.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2018Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
Abstract
Human serum transferrin (sTf) is a protein that mediates the transport of iron from blood to cells. Assisted by the synergistic anion carbonate, sTf transports Fe(III) by binding the metal ion in a closed conformation. Previous studies suggest sTf's role as a potential transporter of other metals such as titanium. Ti is a widely used metal in colorants, foods, and implants. A substantial amount of Ti is leached into blood from these implants. However, the fate of the leached Ti and its transport into the cells is not known. Understanding Ti interaction with sTf assumes a greater significance with our ever increasing exposure to Ti in the form of implants. On the basis of in vitro studies, it was speculated that transferrin can bind Ti(IV) assisted by a synergistic anion. However, the role and identity of the synergistic anion(s) and the conformational state in which sTf binds Ti(IV) are not known. Here we have solved the first X-ray crystal structure of a Ti(IV)-bound sTf. We find that sTf binds Ti(IV) in an open conformation with both carbonate and citrate as synergistic anions at the metal binding sites, an unprecedented role for citrate. Studies with cell lines suggest that Ti(IV)-sTf is transported into cells and that sTf and citrate regulate the metal's blood speciation and attenuate its cytotoxic property. Our results provide the first glimpse into the citrate-transferrin synergism in the regulation of Ti(IV) bioactivity and offers insight into the future design of Ti(IV)-based anticancer drugs.
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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.