Role of Alkali Metal Ions in G-Quadruplex Nucleic Acid Structure and Stability

G-quadruplexes constitute an important type of nucleic acid structure, which can be found in living cells and applied by cell machinery as pivotal regulatory elements. Importantly, robust development of SELEX technology and modern, nucleic acid-based therapeutic strategies targeted towards various molecules have also revealed a large group of potent aptamers whose structures are grounded in G-quadruplexes. In this review, we analyze further extension of tetraplexes by additional structural elements and investigate whether G-quadruplex junctions with duplex, hairpin, triplex, or second G-quadruplex motifs are favorable for aptamers stability and biological activity. Furthermore, we indicate the specific and pivotal role of the G-quadruplex domain and the additional structural elements in interactions with target molecules. Finally, we consider the potency of G-quadruplex junctions in future applications and indicate the emerging research area that is still waiting for development to obtain highly specific and effective nucleic acid-based molecular tools.

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Tuning the Voltage Dependence of Tetraethylammonium Block with Permeant Ions in an Inward-Rectifier K+ Channel

The Journal of General Physiology ◽

10.1085/jgp.114.3.415 ◽

1999 ◽

Vol 114 (3) ◽

pp. 415-426 ◽

Cited By ~ 34

Author(s):

Maria Spassova ◽

Zhe Lu

Keyword(s):

Alkali Metal ◽

Metal Ions ◽

Ion Selectivity ◽

Inward Rectifier ◽

K Channel ◽

Alkali Metal Ions ◽

Internal Site ◽

External Site ◽

Ion Binding Sites

To understand the role of permeating ions in determining blocking ion–induced rectification, we examined block of the ROMK1 inward-rectifier K+ channel by intracellular tetraethylammonium in the presence of various alkali metal ions in both the extra- and intracellular solutions. We found that the channel exhibits different degrees of rectification when different alkali metal ions (all at 100 mM) are present in the extra- and intracellular solution. A quantitative analysis shows that an external ion site in the ROMK1 pore binds various alkali metal ions (Na+, K+, Rb+, and Cs+) with different affinities, which can in turn be altered by the binding of different permeating ions at an internal site through a nonelectrostatic mechanism. Consequently, the external site is saturated to a different level under the various ionic conditions. Since rectification is determined by the movement of all energetically coupled ions in the transmembrane electrical field along the pore, different degrees of rectification are observed in various combinations of extra- and intracellular permeant ions. Furthermore, the external and internal ion-binding sites in the ROMK1 pore appear to have different ion selectivity: the external site selects strongly against the smaller Na+, but only modestly among the three larger ions, whereas the internal site interacts quite differently with the larger K+ and Rb+ ions.

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Kinetics and mechanism of the reduction of dodecatungstocobaltate(III) by oxalate. The catalytic role of alkali metal ions through outer-sphere bridging

Journal of the Chemical Society Dalton Transactions ◽

10.1039/dt9860001301 ◽

1986 ◽

pp. 1301 ◽

Cited By ~ 14

Author(s):

Swapan K. Saha ◽

Manik C. Ghosh ◽

Pradyot Banerjee

Keyword(s):

Alkali Metal ◽

Metal Ions ◽

Outer Sphere ◽

Kinetics And Mechanism ◽

Alkali Metal Ions ◽

Catalytic Role

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Native de novo structural determinations of non-canonical nucleic acid motifs by X-ray crystallography at long wavelengths

Nucleic Acids Research ◽

10.1093/nar/gkaa439 ◽

2020 ◽

Vol 48 (17) ◽

pp. 9886-9898

Author(s):

Yashu Zhang ◽

Kamel El Omari ◽

Ramona Duman ◽

Sisi Liu ◽

Shozeb Haider ◽

...

Keyword(s):

Nucleic Acid ◽

Pseudorabies Virus ◽

De Novo ◽

Telomeric Sequence ◽

Anomalous Scattering ◽

Nucleic Acid Structure ◽

X Ray ◽

G Quadruplex ◽

Structure Determinations ◽

Acid Structure

Abstract Obtaining phase information remains a formidable challenge for nucleic acid structure determination. The introduction of an X-ray synchrotron beamline designed to be tunable to long wavelengths at Diamond Light Source has opened the possibility to native de novo structure determinations by the use of intrinsic scattering elements. This provides opportunities to overcome the limitations of introducing modifying nucleotides, often required to derive phasing information. In this paper, we build on established methods to generate new tools for nucleic acid structure determinations. We report on the use of (i) native intrinsic potassium single-wavelength anomalous dispersion methods (K-SAD), (ii) use of anomalous scattering elements integral to the crystallization buffer (extrinsic cobalt and intrinsic potassium ions), (iii) extrinsic bromine and intrinsic phosphorus SAD to solve complex nucleic acid structures. Using the reported methods we solved the structures of (i) Pseudorabies virus (PRV) RNA G-quadruplex and ligand complex, (ii) PRV DNA G-quadruplex, and (iii) an i-motif of human telomeric sequence. Our results highlight the utility of using intrinsic scattering as a pathway to solve and determine non-canonical nucleic acid motifs and reveal the variability of topology, influence of ligand binding, and glycosidic angle rearrangements seen between RNA and DNA G-quadruplexes of the same sequence.

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