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Nucleic Acids Research Jun 2022The structure and properties of DNA depend on the environment, in particular the ion atmosphere. Here, we investigate how DNA twist -one of the central properties of...
The structure and properties of DNA depend on the environment, in particular the ion atmosphere. Here, we investigate how DNA twist -one of the central properties of DNA- changes with concentration and identity of the surrounding ions. To resolve how cations influence the twist, we combine single-molecule magnetic tweezer experiments and extensive all-atom molecular dynamics simulations. Two interconnected trends are observed for monovalent alkali and divalent alkaline earth cations. First, DNA twist increases monotonously with increasing concentration for all ions investigated. Second, for a given salt concentration, DNA twist strongly depends on cation identity. At 100 mM concentration, DNA twist increases as Na+ < K+ < Rb+ < Ba2+ < Li+ ≈ Cs+ < Sr2+ < Mg2+ < Ca2+. Our molecular dynamics simulations reveal that preferential binding of the cations to the DNA backbone or the nucleobases has opposing effects on DNA twist and provides the microscopic explanation of the observed ion specificity. However, the simulations also reveal shortcomings of existing force field parameters for Cs+ and Sr2+. The comprehensive view gained from our combined approach provides a foundation for understanding and predicting cation-induced structural changes both in nature and in DNA nanotechnology.
Topics: Cations; Cations, Divalent; Cations, Monovalent; DNA; Molecular Dynamics Simulation; Sodium; Sodium Chloride
PubMed: 35640616
DOI: 10.1093/nar/gkac445 -
Biometals : An International Journal on... Oct 2021Magnesium (Mg) is the 2nd most abundant intracellular cation, which participates in various enzymatic reactions; there by regulating vital biological functions.... (Review)
Review
Magnesium (Mg) is the 2nd most abundant intracellular cation, which participates in various enzymatic reactions; there by regulating vital biological functions. Magnesium (Mg) can regulate several cations, including sodium, potassium, and calcium; it consequently maintains physiological functions like impulse conduction, blood pressure, heart rhythm, and muscle contraction. But, it doesn't get much attention in account with its functions, making it a "Forgotten cation". Like other cations, maintenance of the normal physiological level of Mg is important. Its deficiency is associated with various diseases, which point out to the importance of Mg as a drug. The roles of Mg such as natural calcium antagonist, glutamate NMDA receptor blocker, vasodilator, antioxidant and anti-inflammatory agent are responsible for its therapeutic benefits. Various salts of Mg are currently in clinical use, but their application is limited. This review collates all the possible mechanisms behind the behavior of magnesium as a drug at different disease conditions with clinical shreds of evidence.
Topics: Calcium; Cations; Magnesium; Potassium; Sodium
PubMed: 34213669
DOI: 10.1007/s10534-021-00328-7 -
Pharmacological Reviews Oct 2019Endogenous ions play important roles in the function and pharmacology of G-protein coupled receptors (GPCRs). Historically the evidence for ionic modulation of GPCR... (Review)
Review
Endogenous ions play important roles in the function and pharmacology of G-protein coupled receptors (GPCRs). Historically the evidence for ionic modulation of GPCR function dates to 1973 with studies of opioid receptors, where it was demonstrated that physiologic concentrations of sodium allosterically attenuated agonist binding. This Na-selective effect was distinct from effects of other monovalent and divalent cations, with the latter usually counteracting sodium's negative allosteric modulation of binding. Since then, numerous studies documenting the effects of mono- and divalent ions on GPCR function have been published. While ions can act selectively and nonselectively at many sites in different receptors, the discovery of the conserved sodium ion site in class A GPCR structures in 2012 revealed the unique nature of Na site, which has emerged as a near-universal site for allosteric modulation of class A GPCR structure and function. In this review, we synthesize and highlight recent advances in the functional, biophysical, and structural characterization of ions bound to GPCRs. Taken together, these findings provide a molecular understanding of the unique roles of Na and other ions as GPCR allosteric modulators. We will also discuss how this knowledge can be applied to the redesign of receptors and ligand probes for desired functional and pharmacological profiles. SIGNIFICANCE STATEMENT: The function and pharmacology of GPCRs strongly depend on the presence of mono and divalent ions in experimental assays and in living organisms. Recent insights into the molecular mechanism of this ion-dependent allosterism from structural, biophysical, biochemical, and computational studies provide quantitative understandings of the pharmacological effects of drugs in vitro and in vivo and open new avenues for the rational design of chemical probes and drug candidates with improved properties.
Topics: Allosteric Site; Anions; Binding Sites; Cations, Divalent; Cations, Monovalent; Chlorides; Crystallography, X-Ray; Humans; Ligands; Protein Conformation; Receptors, G-Protein-Coupled; Sodium; Structure-Activity Relationship; Zinc
PubMed: 31551350
DOI: 10.1124/pr.119.017863 -
International Journal of Molecular... Apr 2022NMR is the method of choice for molecular and ionic structures and dynamics investigations. The present review is devoted to solvation and mobilities in solid... (Review)
Review
NMR is the method of choice for molecular and ionic structures and dynamics investigations. The present review is devoted to solvation and mobilities in solid electrolytes, such as ion-exchange membranes and composite materials, based on cesium acid sulfates and phosphates. The applications of high-resolution NMR, solid-state NMR, NMR relaxation, and pulsed field gradient H, Li, C, F, Na, P, and Cs NMR techniques are discussed. The main attention is paid to the transport channel morphology, ionic hydration, charge group and mobile ion interaction, and translation ions and solvent mobilities in different spatial scales. Self-diffusion coefficients of protons and Li, Na, and Cs cations are compared with the ionic conductivity data. The microscopic ionic transfer mechanism is discussed.
Topics: Cations; Electrolytes; Lithium; Magnetic Resonance Spectroscopy; Protons; Sodium
PubMed: 35563404
DOI: 10.3390/ijms23095011 -
International Journal of Molecular... May 2023Redox properties of monoiminoacenaphthenes (MIANs) were studied using various electrochemical techniques. The potential values obtained were used for calculating the...
Redox properties of monoiminoacenaphthenes (MIANs) were studied using various electrochemical techniques. The potential values obtained were used for calculating the electrochemical gap value and corresponding frontier orbital difference energy. The first-peak-potential reduction of the MIANs was performed. As a result of controlled potential electrolysis, two-electron one-proton addition products were obtained. Additionally, the MIANs were exposed to one-electron chemical reduction by sodium and NaBH. Structures of three new sodium complexes, three products of electrochemical reduction, and one product of the reduction by NaBH were studied using single-crystal X-ray diffraction. The MIANs reduced electrochemically by NaBH represent salts, in which the protonated MIAN skeleton acts as an anion and BuN or Na as a cation. In the case of sodium complexes, the anion radicals of MIANs are coordinated with sodium cations into tetranuclear complexes. The photophysical and electrochemical properties of all reduced MIAN products, as well as neutral forms, were studied both experimentally and quantum-chemically.
Topics: Oxidation-Reduction; Anions; Cations; Sodium
PubMed: 37240012
DOI: 10.3390/ijms24108667 -
F1000Research 2019As their name implies, cation channels allow the regulated flow of cations such as sodium, potassium, calcium, and magnesium across cellular and intracellular membranes.... (Review)
Review
As their name implies, cation channels allow the regulated flow of cations such as sodium, potassium, calcium, and magnesium across cellular and intracellular membranes. Cation channels have long been known for their fundamental roles in controlling membrane potential and excitability in neurons and muscle. In this review, we provide an update on the recent advances in our understanding of the structure-function relationship and the physiological and pathophysiological role of cation channels. The most exciting developments in the last two years, in our opinion, have been the insights that cryoelectron microscopy has provided into the inner life and the gating of not only voltage-gated channels but also mechanosensitive and calcium- or sodium-activated channels. The mechanosensitive Piezo channels especially have delighted the field not only with a fascinating new type of structure but with important roles in blood pressure regulation and lung function.
Topics: Blood Pressure; Calcium; Cations; Cryoelectron Microscopy; Humans; Ion Channels; Lung; Magnesium; Membrane Potentials; Muscles; Neurons; Potassium; Sodium
PubMed: 30755796
DOI: 10.12688/f1000research.17163.1 -
Cells Aug 2022Traumatic spinal cord injury is a life-changing condition with a significant socio-economic impact on patients, their relatives, their caregivers, and even the... (Review)
Review
Traumatic spinal cord injury is a life-changing condition with a significant socio-economic impact on patients, their relatives, their caregivers, and even the community. Despite considerable medical advances, there is still a lack of options for the effective treatment of these patients. The major complexity and significant disabling potential of the pathophysiology that spinal cord trauma triggers are the main factors that have led to incremental scientific research on this topic, including trying to describe the molecular and cellular mechanisms that regulate spinal cord repair and regeneration. Scientists have identified various practical approaches to promote cell growth and survival, remyelination, and neuroplasticity in this part of the central nervous system. This review focuses on specific detailed aspects of the involvement of cations in the cell biology of such pathology and on the possibility of repairing damaged spinal cord tissue. In this context, the cellular biology of sodium, potassium, lithium, calcium, and magnesium is essential for understanding the related pathophysiology and also the possibilities to counteract the harmful effects of traumatic events. Lithium, sodium, potassium-monovalent cations-and calcium and magnesium-bivalent cations-can influence many protein-protein interactions, gene transcription, ion channel functions, cellular energy processes-phosphorylation, oxidation-inflammation, etc. For data systematization and synthesis, we used the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) methodology, trying to make, as far as possible, some order in seeing the "big forest" instead of "trees". Although we would have expected a large number of articles to address the topic, we were still surprised to find only 51 unique articles after removing duplicates from the 207 articles initially identified. Our article integrates data on many biochemical processes influenced by cations at the molecular level to understand the real possibilities of therapeutic intervention-which must maintain a very narrow balance in cell ion concentrations. Multimolecular, multi-cellular: neuronal cells, glial cells, non-neuronal cells, but also multi-ionic interactions play an important role in the balance between neuro-degenerative pathophysiological processes and the development of effective neuroprotective strategies. This article emphasizes the need for studying cation dynamics as an important future direction.
Topics: Calcium; Cations; Humans; Lithium; Magnesium; Potassium; Sodium; Spinal Cord Injuries
PubMed: 36010579
DOI: 10.3390/cells11162503 -
Biochimica Et Biophysica Acta May 2001The review is concerned with three Na(+)-dependent biotin-containing decarboxylases, which catalyse the substitution of CO(2) by H(+) with retention of configuration... (Review)
Review
The review is concerned with three Na(+)-dependent biotin-containing decarboxylases, which catalyse the substitution of CO(2) by H(+) with retention of configuration (DeltaG degrees '=-30 kJ/mol): oxaloacetate decarboxylase from enterobacteria, methylmalonyl-CoA decarboxylase from Veillonella parvula and Propiogenium modestum, and glutaconyl-CoA decarboxylase from Acidaminococcus fermentans. The enzymes represent complexes of four functional domains or subunits, a carboxytransferase, a mobile alanine- and proline-rich biotin carrier, a 9-11 membrane-spanning helix-containing Na(+)-dependent carboxybiotin decarboxylase and a membrane anchor. In the first catalytic step the carboxyl group of the substrate is converted to a kinetically activated carboxylate in N-carboxybiotin. After swing-over to the decarboxylase, an electrochemical Na(+) gradient is generated; the free energy of the decarboxylation is used to translocate 1-2 Na(+) from the inside to the outside, whereas the proton comes from the outside. At high [Na(+)], however, the decarboxylases appear to catalyse a mere Na(+)/Na(+) exchange. This finding has implications for the life of P. modestum in sea water, which relies on the synthesis of ATP via Delta(mu)Na(+) generated by decarboxylation. In many sequenced genomes from Bacteria and Archaea homologues of the carboxybiotin decarboxylase from A. fermentans with up to 80% sequence identity have been detected.
Topics: Bacterial Proteins; Biotin; Carboxy-Lyases; Cations, Monovalent; Decarboxylation; Energy Metabolism; Methylmalonyl-CoA Decarboxylase; Models, Chemical; Protons; Sodium
PubMed: 11248185
DOI: 10.1016/s0005-2728(00)00273-5 -
Metal Ions in Life Sciences 2016The two alkali cations Na(+) and K(+) have similar relative abundances in the earth crust but display very different distributions in the biosphere. In all living...
The two alkali cations Na(+) and K(+) have similar relative abundances in the earth crust but display very different distributions in the biosphere. In all living organisms, K(+) is the major inorganic cation in the cytoplasm, where its concentration (ca. 0.1 M) is usually several times higher than that of Na(+). Accumulation of Na(+) at high concentrations in the cytoplasm results in deleterious effects on cell metabolism, e.g., on photosynthetic activity in plants. Thus, Na(+) is compartmentalized outside the cytoplasm. In plants, it can be accumulated at high concentrations in vacuoles, where it is used as osmoticum. Na(+) is not an essential element in most plants, except in some halophytes. On the other hand, it can be a beneficial element, by replacing K(+) as vacuolar osmoticum for instance. In contrast, K(+) is an essential element. It is involved in electrical neutralization of inorganic and organic anions and macromolecules, pH homeostasis, control of membrane electrical potential, and the regulation of cell osmotic pressure. Through the latter function in plants, it plays a role in turgor-driven cell and organ movements. It is also involved in the activation of enzymes, protein synthesis, cell metabolism, and photosynthesis. Thus, plant growth requires large quantities of K(+) ions that are taken up by roots from the soil solution, and then distributed throughout the plant. The availability of K(+) ions in the soil solution, slowly released by soil particles and clays, is often limiting for optimal growth in most natural ecosystems. In contrast, due to natural salinity or irrigation with poor quality water, detrimental Na(+) concentrations, toxic for all crop species, are present in many soils, representing 6 % to 10 % of the earth's land area. Three families of ion channels (Shaker, TPK/KCO, and TPC) and 3 families of transporters (HAK, HKT, and CPA) have been identified so far as contributing to K(+) and Na(+) transport across the plasmalemma and internal membranes, with high or low ionic selectivity. In the model plant Arabidopsis thaliana, these families gather at least 70 members. Coordination of the activities of these systems, at the cell and whole plant levels, ensures plant K(+) nutrition, use of Na(+) as a beneficial element, and adaptation to saline conditions.
Topics: Carrier Proteins; Cations; Gene Expression Regulation, Plant; Homeostasis; Ion Channels; Plant Proteins; Plants; Potassium; Sodium; Soil; Water
PubMed: 26860305
DOI: 10.1007/978-3-319-21756-7_9 -
IUBMB Life Jan 2018Sodium proton antiporters (or sodium proton exchangers [NHEs]) are a critical family of membrane proteins that exchange sodium for protons across cell membranes. In... (Review)
Review
Sodium proton antiporters (or sodium proton exchangers [NHEs]) are a critical family of membrane proteins that exchange sodium for protons across cell membranes. In yeast and plants, their primary function is to keep the sodium concentration low inside the cytoplasm. One class of NHE constitutively expressed in yeast is the plasma membrane Na /H antiporter, and another class is expressed on the endosomal/vacuolar membrane. At present, four bacterial plasma membrane antiporter structures are known and nuclear magnetic resonance structures are available for the membrane spanning transmembrane helices of mammalian and yeast NHEs. Additionally, a vast amount of mutational data are available on the role of individual amino acids and critical motifs involved in transport. We combine this information to obtain a more detailed picture of the yeast NHE plasma membrane protein and review mechanisms of transport, conserved motifs, unique residues important in function, and regulation of these proteins. The Na /H antiporter of Schizosaccharomyces pombe, SpNHE1, is an interesting model protein in an easy to study system and is representative of fungal Na /H antiporters. © IUBMB Life, 70(1):23-31, 2018.
Topics: Amino Acid Sequence; Binding Sites; Cations, Monovalent; Fungal Proteins; Gene Expression; Ion Transport; Models, Molecular; Protein Binding; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Protein Interaction Domains and Motifs; Protein Multimerization; Protons; Salt Tolerance; Schizosaccharomyces; Sodium; Sodium-Hydrogen Exchangers; Structure-Activity Relationship
PubMed: 29219228
DOI: 10.1002/iub.1701