scholarly journals Ion Selectivity of the Cytoplasmic Binding Sites of the Na,K-ATPase: II. Competition of Various Cations

2001 ◽  
Vol 179 (3) ◽  
pp. 263-273 ◽  
Author(s):  
A. Schneeberger ◽  
H.-J. Apell
Keyword(s):  
Binding Sites ◽  
Ion Selectivity ◽  
Atpase Ii

scholarly journals Fluorine-19 NMR and computational quantification of isoflurane binding to the voltage-gated sodium channel NaChBac

2016 ◽  
Vol 113 (48) ◽  
pp. 13762-13767 ◽  
Author(s):  
Monica N. Kinde ◽  
Vasyl Bondarenko ◽  
Daniele Granata ◽  
Weiming Bu ◽  
Kimberly C. Grasty ◽  
...  
Keyword(s):  
Sodium Channel ◽  
Binding Sites ◽  
Ion Selectivity ◽  
Selectivity Filter ◽  
Inactivation Kinetics ◽  
Voltage Gated Sodium Channel ◽  
Voltage Gated ◽  
Voltage Gated Sodium Channels ◽  
Binding Data ◽  
Quantitative Analyses

Voltage-gated sodium channels (NaV) play an important role in general anesthesia. Electrophysiology measurements suggest that volatile anesthetics such as isoflurane inhibit NaVby stabilizing the inactivated state or altering the inactivation kinetics. Recent computational studies suggested the existence of multiple isoflurane binding sites in NaV, but experimental binding data are lacking. Here we use site-directed placement of19F probes in NMR experiments to quantify isoflurane binding to the bacterial voltage-gated sodium channel NaChBac.19F probes were introduced individually to S129 and L150 near the S4–S5 linker, L179 and S208 at the extracellular surface, T189 in the ion selectivity filter, and all phenylalanine residues. Quantitative analyses of19F NMR saturation transfer difference (STD) spectroscopy showed a strong interaction of isoflurane with S129, T189, and S208; relatively weakly with L150; and almost undetectable with L179 and phenylalanine residues. An orientation preference was observed for isoflurane bound to T189 and S208, but not to S129 and L150. We conclude that isoflurane inhibits NaChBac by two distinct mechanisms: (i) as a channel blocker at the base of the selectivity filter, and (ii) as a modulator to restrict the pivot motion at the S4–S5 linker and at a critical hinge that controls the gating and inactivation motion of S6.

scholarly journals Influx of calcium, strontium, and barium in presynaptic nerve endings.

1982 ◽  
Vol 79 (6) ◽  
pp. 1065-1087 ◽  
Author(s):  
D A Nachshen ◽  
M P Blaustein
Keyword(s):  
Divalent Cation ◽  
Binding Sites ◽  
Divalent Cations ◽  
Ion Selectivity ◽  
Permeability Ratio ◽  
Low Concentrations ◽  
Slow Channel ◽  
Channel Selectivity ◽  
High Concentrations ◽  
Two Phases

Depolarization-induced (potassium-stimulated) influx of 45Ca, 85Sr, and 133Ba was measured in synaptosomes prepared from rat brain. There are two phases of divalent cation entry, "fast" and "slow;" each phase is mediated by channels with distinctive characteristics. The fast channels inactivate (within 1 s) and are blocked by low concentrations (less than 1 micro M) of La. The slow channels do not inactivate (within 10 s), and are blocked by high concentrations (greater than 50 micro M) of La. Divalent cation influx through both channels saturates with increasing concentrations of permeant divalent cation; in addition, each permeant divalent cation species competitively blocks the influx of other permeant species. These results are consistent with the presence of "binding sites" for divalent cations in the fast and slow channels. The Ca:Sr:Ba permeability ratio, determined by measuring the influx of all three species in triple-label experiments, was 6:3:2 for the fast channel and 6:3:1 for the slow channel. A simple model for ion selectivity, based on the presence of a binding site in the channel, could account well for slow and, to some extent, for fast, channel selectivity data.

E2P Phosphoforms of Na,K-ATPase. II. Interaction of Substrate and Cation-Binding Sites in PiPhosphorylation of Na,K-ATPase†

Biochemistry ◽  
1998 ◽  
Vol 37 (47) ◽  
pp. 16686-16696 ◽  
Author(s):  
Flemming Cornelius ◽  
Natalya U. Fedosova ◽  
Irena Klodos
Keyword(s):  
Binding Sites ◽  
Cation Binding ◽  
Atpase Ii

scholarly journals Exploring the structure and function of Thermotoga maritima CorA reveals the mechanism of gating and ion selectivity in Co2+/Mg2+ transport

2013 ◽  
Vol 451 (3) ◽  
pp. 365-374 ◽  
Author(s):  
Nurhuda Nordin ◽  
Albert Guskov ◽  
Terri Phua ◽  
Newsha Sahaf ◽  
Yu Xia ◽  
...  
Keyword(s):  
Metal Binding ◽  
Binding Sites ◽  
Metal Ion ◽  
Thermotoga Maritima ◽  
Ion Selectivity ◽  
Metal Binding Sites ◽  
Gating Mechanism ◽  
Structural Details ◽  
And Function ◽  
Conserved Amino Acids

The CorA family of divalent cation transporters utilizes Mg2+ and Co2+ as primary substrates. The molecular mechanism of its function, including ion selectivity and gating, has not been fully characterized. Recently we reported a new structure of a CorA homologue from Methanocaldococcus jannaschii, which provided novel structural details that offered the conception of a unique gating mechanism involving conversion of an open hydrophilic gate into a closed hydrophobic one. In the present study we report functional evidence for this novel gating mechanism in the Thermotoga maritima CorA together with an improved crystal structure of this CorA to 2.7 Å (1 Å=0.1 nm) resolution. The latter reveals the organization of the selectivity filter to be similar to that of M. jannaschii CorA and also the previously unknown organization of the second signature motif of the CorA family. The proposed gating is achieved by a helical rotation upon the binding of a metal ion substrate to the regulatory binding sites. Additionally, our data suggest that the preference of this CorA for Co2+ over Mg2+ is controlled by the presence of threonine side chains in the channel. Finally, the roles of the intracellular metal-binding sites have been assigned to increased thermostability and regulation of the gating. These mechanisms most likely apply to the entire CorA family as they are regulated by the highly conserved amino acids.

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