scholarly journals Duplex formation in a G-quadruplex bulge

2020 ◽  
Vol 48 (18) ◽  
pp. 10567-10575 ◽  
Author(s):  
Thi Quynh Ngoc Nguyen ◽  
Kah Wai Lim ◽  
Anh Tuân Phan
Keyword(s):  
Base Pair ◽  
Solution Structure ◽  
Biological Significance ◽  
Consensus Definition ◽  
Quadruplex Structure ◽  
G Quadruplex ◽  
Structural Details ◽  
The Stability ◽  
Definition Of ◽  
Duplex Formation

Abstract Beyond the consensus definition of G-quadruplex-forming motifs with tracts of continuous guanines, G-quadruplexes harboring bulges in the G-tetrad core are prevalent in the human genome. Here, we study the incorporation of a duplex hairpin within a bulge of a G-quadruplex. The NMR solution structure of a G-quadruplex containing a duplex bulge was resolved, revealing the structural details of the junction between the duplex bulge and the G-quadruplex. Unexpectedly, instead of an orthogonal connection the duplex stem was observed to stack below the G-quadruplex forming a unique quadruplex–duplex junction. Breaking up of the immediate base pair step at the junction, coupled with a narrowing of the duplex groove within the context of the bulge, led to a progressive transition between the quadruplex and duplex segments. This study revealed that a duplex bulge can be formed at various positions of a G-quadruplex scaffold. In contrast to a non-structured bulge, the stability of a G-quadruplex slightly increases with an increase in the duplex bulge size. A G-quadruplex structure containing a duplex bulge of up to 33 nt in size was shown to form, which was much larger than the previously reported 7-nt bulge. With G-quadruplexes containing duplex bulges representing new structural motifs with potential biological significance, our findings would broaden the definition of potential G-quadruplex-forming sequences.

scholarly journals The effect of hairpin loop on the structure and gene expression activity of the long-loop G-quadruplex

2021 ◽  
Author(s):  
Subramaniyam Ravichandran ◽  
Maria Razzaq ◽  
Nazia Parveen ◽  
Ambarnil Ghosh ◽  
Kyeong Kyu Kim
Keyword(s):  
Gene Expression ◽  
Rna Structure ◽  
Biological Significance ◽  
Cellular Functions ◽  
Hairpin Loops ◽  
G Quadruplex ◽  
Reporter Assays ◽  
Expression Activity ◽  
The Stability ◽  
And Function

Abstract G-quadruplex (G4), a four-stranded DNA or RNA structure containing stacks of guanine tetrads, plays regulatory roles in many cellular functions. So far, conventional G4s containing loops of 1–7 nucleotides have been widely studied. Increasing experimental evidence suggests that unconventional G4s, such as G4s containing long loops (long-loop G4s), play a regulatory role in the genome by forming a stable structure. Other secondary structures such as hairpins in the loop might thus contribute to the stability of long-loop G4s. Therefore, investigation of the effect of the hairpin-loops on the structure and function of G4s is required. In this study, we performed a systematic biochemical investigation of model G4s containing long loops with various sizes and structures. We found that the long-loop G4s are less stable than conventional G4s, but their stability increased when the loop forms a hairpin (hairpin-G4). We also verified the biological significance of hairpin-G4s by showing that hairpin-G4s present in the genome also form stable G4s and regulate gene expression as confirmed by in cellulo reporter assays. This study contributes to expanding the scope and diversity of G4s, thus facilitating future studies on the role of G4s in the human genome.

The Effect of Temperature on the Interaction of Phenanthroline-based Ligands with G-quadruplex: In Silico Viewpoint

2019 ◽  
Vol 22 (8) ◽  
pp. 546-554
Author(s):  
Mohadeseh Bazoobandi ◽  
Mohammad R. Bozorgmehr ◽  
Ali Mahmoudi ◽  
Ali Morsali
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulation ◽  
Low Temperatures ◽  
Simulation Method ◽  
Dynamics Simulation ◽  
Effect Of Temperature ◽  
Quadruplex Structure ◽  
G Quadruplex ◽  
The Stability ◽  
Increasing Temperature

Aim and Objective: The stability of the G-quadruplex structure can increase its activity in telomerase inhibiting cancer cells. In this study, a molecular dynamics simulation method was used to study the effect of three phenanthroline-based ligands on the structure of G-quadruplex at the temperatures of 20, 40, 60 and 80°C. Materials and Methods: RMSD values and frequency of calculated RMSD in the presence and absence of ligands show that ligands cause the relative stability of the G-quadruplex, particularly at low temperatures. The calculation of hydrogen bonds in Guanine-tetrads in three different quadruplex sheets shows that the effect of ligands on the sheets is not the same so that the bottom sheet of G-quadruplex is most affected by the ligands at high temperatures, and the Guaninetetrads in this sheet are far away. Conformation factor was calculated as a measure of ligands binding affinity for each of the G-quadruplex residues. Results: The results show that the studied ligands interact more with the G-quadruplex than loop areas, although with increasing temperature, the binding area also includes the G-quadruplex sheets. The contribution of each of the residues involved in the G-quadruplex binding area with ligands was also calculated. Conclusion: The calculations performed are consistent with the previous experimental observations that can help to understand the molecular mechanism of the interaction of phenanthroline and its derivatives with quadruplex.

scholarly journals Effects of Central Loop Length and Metal Ions on the Thermal Stability of G-Quadruplexes

Molecules ◽  
2019 ◽  
Vol 24 (10) ◽  
pp. 1863 ◽  
Author(s):  
Fengjin Hao ◽  
Yushu Ma ◽  
Yifu Guan
Keyword(s):  
Thermal Stability ◽  
Stability Analysis ◽  
Difference Spectrum ◽  
Loop Length ◽  
Rna Sequences ◽  
Quadruplex Structure ◽  
G Quadruplex ◽  
The Stability ◽  
Central Loop ◽  
Uv Melting

The central loop of G-quadruplex molecular beacons is a key element to sense target DNA or RNA sequences. In this study, circular dichroism spectroscopy (CD), thermal difference spectrum (TDS), non-denatured non-denaturing gel electrophoresis, and thermal stability analysis were used to investigate the effect of the central loop length on G-quadruplex features. Two series of G-quadruplexes, AG3TTAG3-(TTA)n-G3TTAG3T (n = 1–8) (named TTA series) and AG3TTTG3-(TTA)n-G3TTTG3T (n = 1–8) (named TTT series) were examined in K+ and Na+ solutions, respectively. CD and TDS spectral data indicated that TTA series adopted an antiparallel G-quadruplex structure in Na+ solution and a hybrid G-quadruplex structure in K+ solution respectively. TTT series exhibited a hybrid G-quadruplex structure in both Na+ and K+ solutions. UV melting curves indicated that the stability of G-quadruplex in both series was reduced by the elongation of central loop. Thermal stability analysis concluded that the G-quadruplex destabilization with long central loop is an entropy-driven process due to more flexible and longer central loops.

scholarly journals NMR solution structure of the major G-quadruplex structure formed in the human BCL2 promoter region

2006 ◽  
Vol 34 (18) ◽  
pp. 5133-5144 ◽  
Author(s):  
Jixun Dai ◽  
Ding Chen ◽  
Roger A. Jones ◽  
Laurence H. Hurley ◽  
Danzhou Yang
Keyword(s):  
Promoter Region ◽  
Solution Structure ◽  
Nmr Solution Structure ◽  
Quadruplex Structure ◽  
G Quadruplex

Postmodern More

Moreana ◽  
2003 ◽  
Vol 40 (Number 153- (1-2) ◽  
pp. 219-239
Author(s):  
Anne Lake Prescott
Keyword(s):  
Human Language ◽  
Thomas More ◽  
The Stability ◽  
Definition Of ◽  
Recent Critic

Thomas More is often called a “humanist,” and rightly so if the word has its usual meaning in scholarship on the Renaissance. “Humanist” has by now acquired so many different and contradictory meanings, however, that it needs to be applied carefully to the likes of More. Many postmodernists tend to use the word, pejoratively, to mean someone who believes in an autonomous self, the stability of words, reason, and the possibility of determinable meanings. Without quite arguing that More was a postmodernist avant la lettre, this essay suggests that he was not a “humanist” who stalks the pages of much recent postmodernist theory and that in fact even while remaining a devout Catholic and sensible lawyer he was quite as aware as any recent critic of the slipperiness of human selves and human language. It is time that literary critics tightened up their definition of “humanist,” especially when writing about the Renaissance.

ECOLOGICAL SIGNIFICANCE OF PHEROMONES

2020 ◽  
Vol 6 (2) ◽  
pp. 64-68
Author(s):  
Nondira Khondhodjayeva ◽  
◽  
Nurmamat Rajabov ◽  
Keyword(s):  
Biological Significance ◽  
Ecological Significance ◽  
Definition Of

This article reveals the essence of the concept of "pheromones" and their biological significance. In the article variants of their application in agriculture for struggle against insects-pests are presented. The definition of term and classification of pheromones and their types are given: feromons of insects, feromons of fish, feromons of vertebrates, feromons of humans, fermons of plants, sexual feromons, anxiety feromons, trace feromons, epidemic feromons and their functions and significance for the representative's organism and the environment as a whole

scholarly journals Influence of study model, baseline catalytic concentrations and analytical system on the stability of serum alanine aminotransferase

2020 ◽  
Vol 1 (2) ◽  
Author(s):  
Josep Miquel Bauça ◽  
Andrea Caballero ◽  
Carolina Gómez ◽  
Débora Martínez-Espartosa ◽  
Isabel García del Pino ◽  
...  
Keyword(s):  
Alanine Aminotransferase ◽  
Experimental Models ◽  
Individual Variability ◽  
Serum Samples ◽  
Multicentric Study ◽  
Different Temperatures ◽  
The Stability ◽  
Analytical System ◽  
Definition Of ◽  
Analytical Platforms

AbstractObjectivesThe stability of the analytes most commonly used in routine clinical practice has been the subject of intensive research, with varying and even conflicting results. Such is the case of alanine aminotransferase (ALT). The purpose of this study was to determine the stability of serum ALT according to different variables.MethodsA multicentric study was conducted in eight laboratories using serum samples with known initial catalytic concentrations of ALT within four different ranges, namely: <50 U/L (<0.83 μkat/L), 50–200 U/L (0.83–3.33 μkat/L), 200–400 U/L (3.33–6.67 μkat/L) and >400 U/L (>6.67 μkat/L). Samples were stored for seven days at two different temperatures using four experimental models and four laboratory analytical platforms. The respective stability equations were calculated by linear regression. A multivariate model was used to assess the influence of different variables.ResultsCatalytic concentrations of ALT decreased gradually over time. Temperature (−4%/day at room temperature vs. −1%/day under refrigeration) and the analytical platform had a significant impact, with Architect (Abbott) showing the greatest instability. Initial catalytic concentrations of ALT only had a slight impact on stability, whereas the experimental model had no impact at all.ConclusionsThe constant decrease in serum ALT is reduced when refrigerated. Scarcely studied variables were found to have a significant impact on ALT stability. This observation, added to a considerable inter-individual variability, makes larger studies necessary for the definition of stability equations.

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