Solution Structure of an Intramolecular (3 + 1) Human Telomeric G-Quadruplex Bound to a Telomestatin Derivative

2013 ◽  
Vol 135 (36) ◽  
pp. 13495-13501 ◽  
Author(s):  
Wan Jun Chung ◽  
Brahim Heddi ◽  
Masayuki Tera ◽  
Keisuke Iida ◽  
Kazuo Nagasawa ◽  
...  
Keyword(s):  
Solution Structure ◽  
G Quadruplex

scholarly journals Overlapping but distinct: a new model for G-quadruplex biochemical specificity

2021 ◽  
Author(s):  
Martin Volek ◽  
Sofia Kolesnikova ◽  
Katerina Svehlova ◽  
Pavel Srb ◽  
Ráchel Sgallová ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Drug Design ◽  
Solution Structure ◽  
Biochemical Data ◽  
Biological Regulation ◽  
New Model ◽  
G Quadruplex ◽  
Range Of Functions ◽  
Nucleic Acid Structures ◽  
Sequence Requirements

Abstract G-quadruplexes are noncanonical nucleic acid structures formed by stacked guanine tetrads. They are capable of a range of functions and thought to play widespread biological roles. This diversity raises an important question: what determines the biochemical specificity of G-quadruplex structures? The answer is particularly important from the perspective of biological regulation because genomes can contain hundreds of thousands of G-quadruplexes with a range of functions. Here we analyze the specificity of each sequence in a 496-member library of variants of a reference G-quadruplex with respect to five functions. Our analysis shows that the sequence requirements of G-quadruplexes with these functions are different from one another, with some mutations altering biochemical specificity by orders of magnitude. Mutations in tetrads have larger effects than mutations in loops, and changes in specificity are correlated with changes in multimeric state. To complement our biochemical data we determined the solution structure of a monomeric G-quadruplex from the library. The stacked and accessible tetrads rationalize why monomers tend to promote a model peroxidase reaction and generate fluorescence. Our experiments support a model in which the sequence requirements of G-quadruplexes with different functions are overlapping but distinct. This has implications for biological regulation, bioinformatics, and drug design.

Solution Structure of a Parallel-stranded G-Quadruplex DNA

1993 ◽  
Vol 234 (4) ◽  
pp. 1171-1183 ◽  
Author(s):  
Yong Wang ◽  
Dinshaw J. Patel
Keyword(s):  
Solution Structure ◽  
Quadruplex Dna ◽  
G Quadruplex

scholarly journals Molecular Recognition of the Hybrid-Type G-Quadruplexes in Human Telomeres

Molecules ◽  
2019 ◽  
Vol 24 (8) ◽  
pp. 1578 ◽  
Author(s):  
Guanhui Wu ◽  
Luying Chen ◽  
Wenting Liu ◽  
Danzhou Yang
Keyword(s):  
Small Molecule ◽  
Solution Structure ◽  
Structural Information ◽  
Rational Drug Design ◽  
Hybrid Type ◽  
G4 Dna ◽  
Rational Drug ◽  
G Quadruplex ◽  
Molecule Recognition ◽  
Dna Secondary Structures

G-quadruplex (G4) DNA secondary structures formed in human telomeres have been shown to inhibit cancer-specific telomerase and alternative lengthening of telomere (ALT) pathways. Thus, human telomeric G-quadruplexes are considered attractive targets for anticancer drugs. Human telomeric G-quadruplexes are structurally polymorphic and predominantly form two hybrid-type G-quadruplexes, namely hybrid-1 and hybrid-2, under physiologically relevant solution conditions. To date, only a handful solution structures are available for drug complexes of human telomeric G-quadruplexes. In this review, we will describe two recent solution structural studies from our labs. We use NMR spectroscopy to elucidate the solution structure of a 1:1 complex between a small molecule epiberberine and the hybrid-2 telomeric G-quadruplex, and the structures of 1:1 and 4:2 complexes between a small molecule Pt-tripod and the hybrid-1 telomeric G-quadruplex. Structural information of small molecule complexes can provide important information for understanding small molecule recognition of human telomeric G-quadruplexes and for structure-based rational drug design targeting human telomeric G-quadruplexes.

Abstract LB-200: Solution structure of c-Myc G-quadruplex complex with a quindoline compound

2011 ◽  
Author(s):  
Jixun Dai ◽  
Megan Carver ◽  
Raveendra I. Mathad ◽  
Lawrence Hurley ◽  
Danzhou Yang
Keyword(s):  
Solution Structure ◽  
G Quadruplex

Abstract 860: Solution structure of a dGMP fill-in G-quadruplex forms in PDGFR-bpromoter

2019 ◽  
Author(s):  
Kaibo Wang ◽  
Jonathan Dickerhoff ◽  
Guanhui Wu ◽  
Clement Lin ◽  
Danzhou Yang
Keyword(s):  
Solution Structure ◽  
G Quadruplex

scholarly journals Insights into G-quadruplex specific recognition by the DEAH-box helicase RHAU: Solution structure of a peptide–quadruplex complex

2015 ◽  
Vol 112 (31) ◽  
pp. 9608-9613 ◽  
Author(s):  
Brahim Heddi ◽  
Vee Vee Cheong ◽  
Herry Martadinata ◽  
Anh Tuân Phan
Keyword(s):  
Electrostatic Interactions ◽  
Solution Structure ◽  
Binding Mode ◽  
Structural Basis ◽  
Cellular Processes ◽  
Charged Amino Acids ◽  
G Quadruplex ◽  
Guanine Base ◽  
Nucleic Acid Structures ◽  
Phosphate Groups

Four-stranded nucleic acid structures called G-quadruplexes have been associated with important cellular processes, which should require G-quadruplex–protein interaction. However, the structural basis for specific G-quadruplex recognition by proteins has not been understood. The DEAH (Asp-Glu-Ala-His) box RNA helicase associated with AU-rich element (RHAU) (also named DHX36 or G4R1) specifically binds to and resolves parallel-stranded G-quadruplexes. Here we identified an 18-amino acid G-quadruplex-binding domain of RHAU and determined the structure of this peptide bound to a parallel DNA G-quadruplex. Our structure explains how RHAU specifically recognizes parallel G-quadruplexes. The peptide covers a terminal guanine base tetrad (G-tetrad), and clamps the G-quadruplex using three-anchor-point electrostatic interactions between three positively charged amino acids and negatively charged phosphate groups. This binding mode is strikingly similar to that of most ligands selected for specific G-quadruplex targeting. Binding to an exposed G-tetrad represents a simple and efficient way to specifically target G-quadruplex structures.

Abstract 860: Solution structure of a dGMP fill-in G-quadruplex forms in PDGFR-bpromoter

2019 ◽  
Author(s):  
Kaibo Wang ◽  
Jonathan Dickerhoff ◽  
Guanhui Wu ◽  
Clement Lin ◽  
Danzhou Yang
Keyword(s):  
Solution Structure ◽  
G Quadruplex

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.

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