ArticleJournal of inorganic biochemistry2013
Metal toxicity and opportunistic binding of Pb(2+) in proteins.
Article in Journal of inorganic biochemistry, 2013. 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, 84 citations in OpenAlex.
- Article
- Ecotoxicological effects of lead in ducks and geese.Veterinary research communications · 2026Review
- Lead-Induced Nephrotoxicity and Its Therapeutic Interventions: An Updated Review.Biological trace element research · 2026Review
- Lead binds HIF-1α contributing to depression-like behaviour through modulating mitochondria-associated astrocyte ferroptosis.Communications biology · 2025Article
- Long-term changes in chemical components in the meadow pipit (Anthus pratensis) in the formerly heavily polluted Eastern Sudetes Mountains.Environmental science and pollution research international · 2025Article
- From coordination to function: Inorganic insights into metalloproteins and metallopeptides in biosystems.Biophysics and physicobiology · 2025Article
- Melatonin as an Ameliorative Agent Against Cadmium- and Lead-Induced Toxicity in Fish: an Overview.Applied biochemistry and biotechnology · 2024Review
- Article
- Early-Life Lead Exposure: Risks and Neurotoxic Consequences.Current medicinal chemistry · 2024Review
- Direct Effects of Toxic Divalent Cations on Contractile Proteins with Implications for the Heart: Unraveling Mechanisms of Dysfunction.International journal of molecular sciences · 2023Review
- Pb(II) coordination to the nonclassical zinc finger tristetraprolin: retained function with an altered fold.Journal of biological inorganic chemistry : JBIC : a publication of the Society of Biological Inorganic Chemistry · 2023Article
- Nanomolar affinity of EF-hands in neuronal calcium sensor 1 for bivalent cations Pb2+, Mn2+, and Hg2.Metallomics : integrated biometal science · 2022Article
- Trace Elements in Breakfast Cereals and Exposure Assessment in Moroccan Population: Case of Lead and Cadmium.Biological trace element research · 2021Article
- MOLECULAR MECHANISMS OF LEAD NEUROTOXICITY.Advances in neurotoxicology · 2021Article
- Structural Aspects and Prediction of Calmodulin-Binding Proteins.International journal of molecular sciences · 2020Review
- Interference of pH buffer with PbMetallomics : integrated biometal science · 2020Article
- Review
- Understanding Graphene Response to Neutral and Charged Lead Species: Theory and Experiment.Materials (Basel, Switzerland) · 2018Article
- Lead poisoning: acute exposure of the heart to lead ions promotes changes in cardiac function and Cav1.2 ion channels.Biophysical reviews · 2017Review
- Lead(II) Binding in Natural and Artificial Proteins.Metal ions in life sciences · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Lead toxicity is associated with various human diseases. While Ca(2+) binding proteins such as calmodulin (CaM) are often reported to be molecular targets for Pb(2+)-binding and lead toxicity, the effect of Pb(2+) on the Ca(2+)/CaM regulated biological activities cannot be described by the primary mechanism of ionic displacement (e.g., ionic mimicry). The focus of this study was to investigate the mechanism of lead toxicity through binding differences between Ca(2+) and Pb(2+) for CaM, an essential intracellular trigger protein with two EF-Hand Ca(2+)-binding sites in each of its two domains that regulates many molecular targets via Ca(2+)-induced conformational change. Fluorescence changes in phenylalanine indicated that Pb(2+) binds with 8-fold higher affinity than Ca(2+) in the N-terminal domain. Additionally, NMR chemical shift changes and an unusual biphasic response observed in tyrosine fluorescence associated with C-terminal domain sites EF-III and EF-IV suggest a single higher affinity Pb(2+)-binding site with a 3-fold higher affinity than Ca(2+), coupled with a second site exhibiting affinity nearly equivalent to that of the N-terminal domain sites. Our results further indicate that Pb(2+) displaces Ca(2+) only in the N-terminal domain, with minimal perturbation of the C-terminal domain, however significant structural/dynamic changes are observed in the trans-domain linker region which appear to be due to Pb(2+)-binding outside of the known calcium-binding sites. These data suggest that opportunistic Pb(2+)-binding in Ca(2+)/CaM has a profound impact on the conformation and dynamics of the essential molecular recognition sites of the central helix, and provides insight into the molecular toxicity of non-essential metal ions.
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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.