NMR Structure of a Triangulenium-Based Long-Lived Fluorescence Probe Bound to a G-Quadruplex

2016 ◽  
Vol 128 (40) ◽  
pp. 12696-12699 ◽  
Author(s):  
Anita Kotar ◽  
Baifan Wang ◽  
Arun Shivalingam ◽  
Jorge Gonzalez-Garcia ◽  
Ramon Vilar ◽  
...  
Keyword(s):  
Fluorescence Probe ◽  
Nmr Structure ◽  
G Quadruplex

NMR Structure of a Triangulenium-Based Long-Lived Fluorescence Probe Bound to a G-Quadruplex

2016 ◽  
Vol 55 (40) ◽  
pp. 12508-12511 ◽  
Author(s):  
Anita Kotar ◽  
Baifan Wang ◽  
Arun Shivalingam ◽  
Jorge Gonzalez-Garcia ◽  
Ramon Vilar ◽  
...  
Keyword(s):  
Fluorescence Probe ◽  
Nmr Structure ◽  
G Quadruplex

scholarly journals Intra-locked G-quadruplex structures formed by irregular DNA G-rich motifs

2020 ◽  
Vol 48 (6) ◽  
pp. 3315-3327 ◽  
Author(s):  
Arijit Maity ◽  
Fernaldo Richtia Winnerdy ◽  
Weili Denyse Chang ◽  
Gang Chen ◽  
Anh Tuân Phan
Keyword(s):  
Human Genome ◽  
Dna Sequences ◽  
Structural Features ◽  
Nmr Structure ◽  
Solution Nmr ◽  
Structural Studies ◽  
High Propensity ◽  
G Quadruplex ◽  
High Prevalence

Abstract G-rich DNA sequences with tracts of three or more continuous guanines (G≥3) are known to have high propensity to adopt stable G-quadruplex (G4) structures. Bioinformatic analyses suggest high prevalence of G-rich sequences with short G-tracts (G≤2) in the human genome. However, due to limited structural studies, the folding principles of such sequences remain largely unexplored and hence poorly understood. Here, we present the solution NMR structure of a sequence named AT26 consisting of irregularly spaced G2 tracts and two isolated single guanines. The structure is a four-layered G4 featuring two bi-layered blocks, locked between themselves in an unprecedented fashion making it a stable scaffold. In addition to edgewise and propeller-type loops, AT26 also harbors two V-shaped loops: a 2-nt V-shaped loop spanning two G-tetrad layers and a 0-nt V-shaped loop spanning three G-tetrad layers, which are named as VS- and VR-loop respectively, based on their distinct structural features. The intra-lock motif can be a basis for extending the G-tetrad core and a very stable intra-locked G4 can be formed by a sequence with G-tracts of various lengths including several G2 tracts. Findings from this study will aid in understanding the folding of G4 topologies from sequences containing irregularly spaced multiple short G-tracts.

NMR structure of dual site binding of mitoxantrone dimer to opposite grooves of parallel stranded G-quadruplex [d-(TTGGGGT)]4

Biochimie ◽  
2016 ◽  
Vol 128-129 ◽  
pp. 59-69 ◽  
Author(s):  
Tarikere Palakshan Pradeep ◽  
Ritu Barthwal
Keyword(s):  
Nmr Structure ◽  
G Quadruplex ◽  
Dual Site ◽  
Site Binding

scholarly journals Solution NMR Structure of a Ligand/Hybrid-2-G-Quadruplex Complex Reveals Rearrangements that Affect Ligand Binding

2017 ◽  
Vol 129 (25) ◽  
pp. 7208-7212 ◽  
Author(s):  
Julia Wirmer-Bartoschek ◽  
Lars Erik Bendel ◽  
Hendrik R. A. Jonker ◽  
J. Tassilo Grün ◽  
Francesco Papi ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Nmr Structure ◽  
Solution Nmr ◽  
G Quadruplex

Simple G-quadruplex-based 2-aminopurine fluorescence probe for highly sensitive and amplified detection of microRNA-21

Talanta ◽  
2018 ◽  
Vol 178 ◽  
pp. 974-979 ◽  
Author(s):  
Shiyu Li ◽  
Chan Liu ◽  
Hang Gong ◽  
Chunyan Chen ◽  
Xiaoming Chen ◽  
...  
Keyword(s):  
Fluorescence Probe ◽  
Highly Sensitive ◽  
G Quadruplex

scholarly journals High-resolution three-dimensional NMR structure of theKRASproto-oncogene promoter reveals key features of a G-quadruplex involved in transcriptional regulation

2017 ◽  
Vol 292 (19) ◽  
pp. 8082-8091 ◽  
Author(s):  
Abdelaziz Kerkour ◽  
Julien Marquevielle ◽  
Stefaniia Ivashchenko ◽  
Liliya A. Yatsunyk ◽  
Jean-Louis Mergny ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
High Resolution ◽  
Three Dimensional ◽  
Nmr Structure ◽  
G Quadruplex ◽  
Key Features

scholarly journals Solution NMR Structure of a Ligand/Hybrid-2-G-Quadruplex Complex Reveals Rearrangements that Affect Ligand Binding

2017 ◽  
Vol 56 (25) ◽  
pp. 7102-7106 ◽  
Author(s):  
Julia Wirmer-Bartoschek ◽  
Lars Erik Bendel ◽  
Hendrik R. A. Jonker ◽  
J. Tassilo Grün ◽  
Francesco Papi ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Nmr Structure ◽  
Solution Nmr ◽  
G Quadruplex

scholarly journals Ligand Selectivity in the Recognition of Protoberberine Alkaloids by Hybrid-2 Human Telomeric G-Quadruplex: Binding Free Energy Calculation, Fluorescence Binding, and NMR Experiments

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1574 ◽  
Author(s):  
Nanjie Deng ◽  
Junchao Xia ◽  
Lauren Wickstrom ◽  
Clement Lin ◽  
Kaibo Wang ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Binding Free Energy ◽  
Nmr Structure ◽  
Free Energy Calculation ◽  
Energy Calculation ◽  
Ligand Selectivity ◽  
Protoberberine Alkaloids ◽  
Binding Free Energy Calculation ◽  
G Quadruplex

The human telomeric G-quadruplex (G4) is an attractive target for developing anticancer drugs. Natural products protoberberine alkaloids are known to bind human telomeric G4 and inhibit telomerase. Among several structurally similar protoberberine alkaloids, epiberberine (EPI) shows the greatest specificity in recognizing the human telomeric G4 over duplex DNA and other G4s. Recently, NMR study revealed that EPI recognizes specifically the hybrid-2 form human telomeric G4 by inducing large rearrangements in the 5′-flanking segment and loop regions to form a highly extensive four-layered binding pocket. Using the NMR structure of the EPI-human telomeric G4 complex, here we perform molecular dynamics free energy calculations to elucidate the ligand selectivity in the recognition of protoberberines by the human telomeric G4. The MM-PB(GB)SA (molecular mechanics-Poisson Boltzmann/Generalized Born) Surface Area) binding free energies calculated using the Amber force fields bsc0 and OL15 correlate well with the NMR titration and binding affinity measurements, with both calculations correctly identifying the EPI as the strongest binder to the hybrid-2 telomeric G4 wtTel26. The results demonstrated that accounting for the conformational flexibility of the DNA-ligand complexes is crucially important for explaining the ligand selectivity of the human telomeric G4. While the MD-simulated (molecular dynamics) structures of the G-quadruplex-alkaloid complexes help rationalize why the EPI-G4 interactions are optimal compared with the other protoberberines, structural deviations from the NMR structure near the binding site are observed in the MD simulations. We have also performed binding free energy calculation using the more rigorous double decoupling method (DDM); however, the results correlate less well with the experimental trend, likely due to the difficulty of adequately sampling the very large conformational reorganization in the G4 induced by the protoberberine binding.

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