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Biophysical Journal Apr 2023The functional properties of some biological ion channels and membrane transport proteins are proposed to exploit anion-hydrophobic interactions. Here, we investigate a...
The functional properties of some biological ion channels and membrane transport proteins are proposed to exploit anion-hydrophobic interactions. Here, we investigate a chloride-pumping rhodopsin as an example of a membrane protein known to contain a defined anion binding site composed predominantly of hydrophobic residues. Using molecular dynamics simulations, we explore Cl- binding to this hydrophobic site and compare the dynamics arising when electronic polarization is neglected (CHARMM36 [c36] fixed-charge force field), included implicitly (via the prosECCo force field), or included explicitly (through the polarizable force field, AMOEBA). Free energy landscapes of Cl- moving out of the binding site and into bulk solution demonstrate that the inclusion of polarization results in stronger ion binding and a second metastable binding site in chloride-pumping rhodopsin. Simulations focused on this hydrophobic binding site also indicate longer binding durations and closer ion proximity when polarization is included. Furthermore, simulations reveal that Cl- within this binding site interacts with an adjacent loop to facilitate rebinding events that are not observed when polarization is neglected. These results demonstrate how the inclusion of polarization can influence the behavior of anions within protein binding sites and can yield results comparable with more accurate and computationally demanding methods.
Topics: Chlorides; Rhodopsin; Anions; Molecular Dynamics Simulation; Electronics
PubMed: 36945777
DOI: 10.1016/j.bpj.2023.03.026 -
The Journal of Physical Chemistry. B Feb 2018The interactions between nonpolar surfaces and polarizable anions lie in a gray area between the hydrophobic and Hofmeister effects. To assess the affinity of these...
The interactions between nonpolar surfaces and polarizable anions lie in a gray area between the hydrophobic and Hofmeister effects. To assess the affinity of these interactions, NMR and ITC were used to probe the thermodynamics of eight anions binding to four different hosts whose pockets each consist primarily of hydrocarbon. Two classes of host were examined: cavitands and cyclodextrins. For all hosts, anion affinity was found to follow the Hofmeister series, with associations ranging from 1.6-5.7 kcal mol. Despite the fact that cavitand hosts 1 and 2 possess intrinsic negative electrostatic fields, it was determined that these more enveloping hosts generally bound anions more strongly. The observation that the four hosts each possess specific anion affinities that cannot be readily explained by their structures, points to the importance of counter cations and the solvation of the "empty" hosts, free guests, and host-guest complexes, in defining the affinity.
Topics: Anions; Calorimetry; Cyclodextrins; Ethers, Cyclic; Magnetic Resonance Spectroscopy; Molecular Structure; Resorcinols; Static Electricity; Thermodynamics
PubMed: 29373793
DOI: 10.1021/acs.jpcb.7b12259 -
Molecules (Basel, Switzerland) Dec 2020A calix-shaped polyoxometalate, [VO] (), stabilizes an anion moiety in its central cavity. This molecule-sized container has the potential to control the reactivity of...
A calix-shaped polyoxometalate, [VO] (), stabilizes an anion moiety in its central cavity. This molecule-sized container has the potential to control the reactivity of an anion. The highly-reactive cyanate is smoothly trapped by to form [VO(CN)]. In the CHNO solution, cyanate abstracts protons from CHNO, and the resultant CHNO is stabilized in to form [VO(CHNO)] (). A crystallographic analysis revealed the double-bond characteristic short bond distance of 1.248 Å between the carbon and nitrogen atoms in the nitromethane anion in . H and C NMR studies showed that the nitromethane anion in must not be exchanged with the nitromethane solvent. Thus, the container restrains the reactivity of anionic species.
Topics: Anions; Calixarenes; Inorganic Chemicals; Methane; Models, Molecular; Molecular Structure; Nitroparaffins; Solvents
PubMed: 33271966
DOI: 10.3390/molecules25235670 -
International Journal of Molecular... Apr 2020We first explore negative-ion formation in fullerenes C to C through low-energy electron elastic scattering total cross sections calculations using our Regge-pole...
We first explore negative-ion formation in fullerenes C to C through low-energy electron elastic scattering total cross sections calculations using our Regge-pole methodology. Then, the formed negative ions C to C are used to investigate the catalysis of water oxidation to peroxide and water synthesis from H and O. The exploited fundamental mechanism underlying negative-ion catalysis involves hydrogen bond strength-weakening/breaking in the transition state. Density Functional Theory transition state calculations found C optimal for both water and peroxide synthesis, C increases the energy barrier the most, and C the most effective catalyst in both water synthesis and oxidation to HO.
Topics: Algorithms; Anions; Catalysis; Electrons; Fullerenes; Models, Chemical; Oxidation-Reduction; Water
PubMed: 32365766
DOI: 10.3390/ijms21093159 -
The Journal of Physiological Sciences :... Jan 2024The volume-sensitive outwardly rectifying or volume-regulated anion channel, VSOR/VRAC, which was discovered in 1988, is expressed in most vertebrate cell types and is... (Review)
Review
The volume-sensitive outwardly rectifying or volume-regulated anion channel, VSOR/VRAC, which was discovered in 1988, is expressed in most vertebrate cell types and is essentially involved in cell volume regulation after swelling and in the induction of cell death. This series of review articles describes what is already known and what remains to be uncovered about the functional and molecular properties as well as the physiological and pathophysiological roles of VSOR/VRAC. This Part 1 review article describes, from the physiological standpoint, first its discovery and significance in cell volume regulation, second its phenotypical properties, and third its molecular identification. Although the pore-forming core molecules and the volume-sensing subcomponent of VSOR/VRAC were identified as LRRC8 members and TRPM7 in 2014 and 2021, respectively, it is stressed that the identification of the molecular entity of VSOR/VRAC is still not complete enough to explain the full set of phenotypical properties.
Topics: Ion Channels; Membrane Proteins; Anions; Cell Size
PubMed: 38238667
DOI: 10.1186/s12576-023-00897-x -
Journal of the American Chemical Society Mar 2022Hofmeister effects have often been ignored in living organisms, although they affect the activity and functions of biological molecules. Herein, amperometry has been...
Hofmeister effects have often been ignored in living organisms, although they affect the activity and functions of biological molecules. Herein, amperometry has been applied to show that the vesicular content, dynamics of exocytosis and vesicles opening, depend on the anionic species treatment. Compared to 100 μM Cl treated chromaffin cells, a similar number of catecholamine molecules is released after chaotropic anions (ClO and SCN) treatment, even though the vesicular catecholamine content significantly increases, suggesting a lower release fraction. In addition, there are opposite effects on the dynamics of vesicles release (shorter duration) and vesicle opening (longer duration) for chaotropic anions treated cells. Our results show anion-dependent vesicle release, vesicle opening, and vesicular content, providing understanding of the pharmacological and pathological processes induced by inorganic ions.
Topics: Anions; Catecholamines; Chromaffin Cells; Exocytosis
PubMed: 35254807
DOI: 10.1021/jacs.2c00581 -
Organic & Biomolecular Chemistry Jan 2022Sulfotransferases constitute a ubiquitous class of enzymes which are poorly understood due to the lack of a convenient tool for screening their activity. These enzymes...
Sulfotransferases constitute a ubiquitous class of enzymes which are poorly understood due to the lack of a convenient tool for screening their activity. These enzymes use the anion PAPS (adenosine-3'-phosphate-5'-phosphosulfate) as a donor for a broad range of acceptor substrates, including carbohydrates, producing sulfated compounds and PAP (adenosine-3',5'-diphosphate) as a side product. We present a europium(III)-based probe that binds reversibly to both PAPS and PAP, producing a larger luminescence enhancement with the latter anion. We exploit this greater emission enhancement with PAP to demonstrate the first direct real-time assay of a heparan sulfate sulfotransferase using a multi-well plate format. The selective response of our probe towards PAP over structurally similar nucleoside phosphate anions, and over other anions, is investigated and discussed. This work opens the possibility of investigating more fully the roles played by this enzyme class in health and disease, including operationally simple inhibitor screening.
Topics: Anions; Cations; Coordination Complexes; Europium; Molecular Structure; Phosphoadenosine Phosphosulfate; Sulfotransferases; Time Factors
PubMed: 34951618
DOI: 10.1039/d1ob02071d -
The Journal of General Physiology Jun 1988Isolated human neutrophils possess three distinct pathways by which Cl- crosses the plasma membrane of steady state cells: anion exchange, active transport, and... (Review)
Review
Isolated human neutrophils possess three distinct pathways by which Cl- crosses the plasma membrane of steady state cells: anion exchange, active transport, and electrodiffusion. The purpose of the present work was to investigate the selectivity of each of these separate processes with respect to other external halide ions. (a) The bulk of total anion movements represents transport through an electrically silent anion-exchange mechanism that is insensitive to disulfonic stilbenes, but which can be competitively inhibited by alpha-cyano-4-hydroxycinnamate (CHC; Ki approximately 0.3 mM). The affinity of the external translocation site of the carrier for each of the different anions was determined (i) from substrate competition between Cl- and either Br-, F-, or I-, (ii) from trans stimulation of 36Cl- efflux as a function of the external concentrations of these anions, (iii) from changes in the apparent Ki for CHC depending on the nature of the replacement anion in the bathing medium, and (iv) from activation of 82Br- and 125I- influxes by their respective ions. Each was bound and transported at roughly similar rates (Vmax values all 1.0-1.4 meq/liter cell water.min); the order of decreasing affinities is Cl- greater than Br- greater than F- greater than I- (true Km values of 5, 9, 23, and 44 mM, respectively). These anions undergo 1:1 countertransport for internal Cl-. (b) There is a minor component of total Cl- influx that constitutes an active inward transport system for the intracellular accumulation of Cl- [( Cl-]i approximately 80 meq/liter cell water), fourfold higher than expected for passive distribution. This uptake is sensitive to intracellular ATP depletion by 2-deoxy-D-glucose and can be inhibited by furosemide, ethacrynic acid, and CHC, which also blocks anion exchange. This active Cl- uptake process binds and transports other members of the halide series in the sequence Cl- greater than Br- greater than I- greater than F- (Km values of 5, 8, 15, and 41 mM, respectively). (c) Electrodiffusive fluxes are small. CHC-resistant 82Br- and 125I- influxes behave as passive leak fluxes through low-conductance ion channels: they are nonsaturable and strongly voltage dependent. These anions permeate the putative Cl- channel in the sequence I- greater than Br- greater than Cl- with relative permeability ratios of 2.2:1.4:1, respectively, where PCl approximately 5 X 10(-9) cm/s.
Topics: Anions; Biological Transport; Biological Transport, Active; Bromides; Cell Membrane Permeability; Chlorides; Diffusion; Drug Interactions; Fluorides; Humans; Iodides; Ion Exchange; Neutrophils
PubMed: 3047312
DOI: 10.1085/jgp.91.6.835 -
Kidney International Jun 1996The renal proximal tubule actively transports charged, potentially toxic xenobiotics from blood to lumen. Basolateral uptake of organic anions is indirectly coupled to... (Review)
Review
The renal proximal tubule actively transports charged, potentially toxic xenobiotics from blood to lumen. Basolateral uptake of organic anions is indirectly coupled to the sodium gradient through Na-dicarboxylate cotransport and dicarboxylate-organic anion exchange. Upon entry, a significant fraction of intracellular organic anion is sequestered within vesicles. Disruption of the cellular microtubular network can lead to both diminished vesicular movement and reduced transepithelial secretion. Luminal efflux of organic anions is energetically downhill, but carrier mediated. Both anion exchange and potential driven transport are present, but neither completely accounts for transport from cell to lumen. For organic cations, basolateral entry is downhill via potential driven facilitated diffusion. Intracellular sequestration of organic cations in vesicles is substantial, but its role in secretion is uncertain. Multiple carriers are available to drive organic cations uphill into the tubular lumen. The classical system indirectly taps the energy of the luminal Na gradient to drive organic cation efflux via Na(+)-H+ and proton-organic cation exchange. In addition, the multidrug resistance ATPase can pump organic cations into the tubular lumen. Thus, although much detailed information has been added over the last 50 years, it is not yet possible to provide a detailed, quantitative understanding of these important excretory systems.
Topics: Animals; Anions; Biological Transport; Cations; Kidney
PubMed: 8743470
DOI: 10.1038/ki.1996.240 -
Plant Physiology Apr 2021Anionic phospholipids include phosphatidic acid (PA), phosphatidylserine (PS), phosphatidylinositol (PI), and its phosphorylated derivatives the phosphoinositides (e.g....
Anionic phospholipids include phosphatidic acid (PA), phosphatidylserine (PS), phosphatidylinositol (PI), and its phosphorylated derivatives the phosphoinositides (e.g. phosphatidylinositol-4-phosphate [PI4P] and phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2]). Although anionic phospholipids are low-abundant lipids, they are particularly important for membrane functions. In particular, anionic lipids act as biochemical and biophysical landmarks that contribute to the establishment of membrane identity, signaling activities, and compartment morphodynamics. Each anionic lipid accumulates in different endomembranes according to a unique subcellular pattern, where they locally provide docking platforms for proteins. As such, they are mostly believed to act in the compartments in which they accumulate. However, mounting evidence throughout eukaryotes suggests that anionic lipids are not as compartment-specific as initially thought and that they are instead organized as concentration gradients across different organelles. In this update, we review the evidence for the existence of anionic lipid gradients in plants. We then discuss the possible implication of these gradients in lipid dynamics and homeostasis, and also in coordinating subcellular activities. Finally, we introduce the notion that anionic lipid gradients at the cellular scale may translate into gradients at the tissue level, which could have implications for plant development.
Topics: Anions; Biosynthetic Pathways; Cell Membrane; Phospholipids; Plant Development; Plant Physiological Phenomena; Plants
PubMed: 33793905
DOI: 10.1093/plphys/kiaa056