scholarly journals Solution Structure of a MYC Promoter G-Quadruplex with 1:6:1 Loop Length

ACS Omega ◽  
2019 ◽  
Vol 4 (2) ◽  
pp. 2533-2539 ◽  
Author(s):  
Jonathan Dickerhoff ◽  
Buket Onel ◽  
Luying Chen ◽  
Yuwei Chen ◽  
Danzhou Yang
Keyword(s):  
Solution Structure ◽  
Loop Length ◽  
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 G-quadruplex conformation and dynamics are determined by loop length and sequence

2014 ◽  
Vol 42 (12) ◽  
pp. 8106-8114 ◽  
Author(s):  
Ramreddy Tippana ◽  
Weikun Xiao ◽  
Sua Myong
Keyword(s):  
Loop Length ◽  
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.

scholarly journals A Sequence-Independent Analysis of the Loop Length Dependence of Intramolecular RNA G-Quadruplex Stability and Topology

Biochemistry ◽  
2011 ◽  
Vol 50 (33) ◽  
pp. 7251-7258 ◽  
Author(s):  
Amy Y. Q. Zhang ◽  
Anthony Bugaut ◽  
Shankar Balasubramanian
Keyword(s):  
Loop Length ◽  
Length Dependence ◽  
And Topology ◽  
Independent Analysis ◽  
G Quadruplex

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

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 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.

Sign in / Sign up

Export Citation Format

Share Document