scholarly journals Dynamics Studies of DNA with Non-canonical Structure Using NMR Spectroscopy

2020 ◽  
Vol 21 (8) ◽  
pp. 2673 ◽  
Author(s):  
Kwang-Im Oh ◽  
Jinwoo Kim ◽  
Chin-Ju Park ◽  
Joon-Hwa Lee
Keyword(s):  
Nmr Spectroscopy ◽  
Biological Function ◽  
Conformational Exchange ◽  
Biological Processes ◽  
Dynamic Characterization ◽  
Dynamic Features ◽  
Dna Structures ◽  
Left Handed ◽  
G Quadruplex ◽  
Insight Into

The non-canonical structures of nucleic acids are essential for their diverse functions during various biological processes. These non-canonical structures can undergo conformational exchange among multiple structural states. Data on their dynamics can illustrate conformational transitions that play important roles in folding, stability, and biological function. Here, we discuss several examples of the non-canonical structures of DNA focusing on their dynamic characterization by NMR spectroscopy: (1) G-quadruplex structures and their complexes with target proteins; (2) i-motif structures and their complexes with proteins; (3) triplex structures; (4) left-handed Z-DNAs and their complexes with various Z-DNA binding proteins. This review provides insight into how the dynamic features of non-canonical DNA structures contribute to essential biological processes.

scholarly journals Subtle structural alterations in G-quadruplex DNA regulate site specificity of fluorescence light-up probes

2020 ◽  
Vol 48 (3) ◽  
pp. 1108-1119 ◽  
Author(s):  
Rajendra Kumar ◽  
Karam Chand ◽  
Sudipta Bhowmik ◽  
Rabindra Nath Das ◽  
Snehasish Bhattacharjee ◽  
...  
Keyword(s):  
Rational Design ◽  
Dna Structure ◽  
Biological Processes ◽  
Chemical Research ◽  
Quadruplex Dna ◽  
Dna Structures ◽  
Future Studies ◽  
G4 Dna ◽  
G Quadruplex ◽  
Fluorescence Light

Abstract G-quadruplex (G4) DNA structures are linked to key biological processes and human diseases. Small molecules that target specific G4 DNA structures and signal their presence would therefore be of great value as chemical research tools with potential to further advance towards diagnostic and therapeutic developments. However, the development of these types of specific compounds remain as a great challenge. In here, we have developed a compound with ability to specifically signal a certain c-MYC G4 DNA structure through a fluorescence light-up mechanism. Despite the compound's two binding sites on the G4 DNA structure, only one of them result in the fluorescence light-up effect. This G-tetrad selectivity proved to originate from a difference in flexibility that affected the binding affinity and tilt the compound out of the planar conformation required for the fluorescence light-up mechanism. The intertwined relation between the presented factors is likely the reason for the lack of examples using rational design to develop compounds with turn-on emission that specifically target certain G4 DNA structures. However, this study shows that it is indeed possible to develop such compounds and present insights into the molecular details of specific G4 DNA recognition and signaling to advance future studies of G4 biology.

scholarly journals N-methyl mesoporphyrin IX as a highly selective light-up probe for G-quadruplex DNA

2019 ◽  
Vol 23 (11n12) ◽  
pp. 1195-1215 ◽  
Author(s):  
Ariana Yett ◽  
Linda Yingqi Lin ◽  
Dana Beseiso ◽  
Joanne Miao ◽  
Liliya A. Yatsunyk
Keyword(s):  
Optical Properties ◽  
Small Molecules ◽  
Genomic Stability ◽  
Water Soluble ◽  
Biological Processes ◽  
Binding Properties ◽  
Quadruplex Dna ◽  
Dna Structures ◽  
G Quadruplex ◽  
High Fluorescence

[Formula: see text]-methyl mesoporphyrin IX (NMM) is a water-soluble, non-symmetric porphyrin with excellent optical properties and unparalleled selectivity for G-quadruplex (GQ) DNA. G-quadruplexes are non-canonical DNA structures formed by guanine-rich sequences. They are implicated in genomic stability, longevity, and cancer. The ability of NMM to selectively recognize GQ structures makes it a valuable scaffold for designing novel GQ binders. In this review, we survey the literature describing the GQ-binding properties of NMM as well as its wide utility in chemistry and biology. We start with the discovery of the GQ-binding properties of NMM and the development of NMM-binding aptamers. We then discuss the optical properties of NMM, focusing on the light-switch effect — high fluorescence of NMM induced upon its binding to GQ DNA. Additionally, we examine the affinity and selectivity of NMM for GQs, as well as its ability to stabilize GQ structures and favor parallel GQ conformations. Furthermore, a portion of the review is dedicated to the applications of NMM-GQ complexes as biosensors for heavy metals, small molecules ([Formula: see text] ATP and pesticides), DNA, and proteins. Finally and importantly, we discuss the utility of NMM as a probe to investigate the roles of GQs in biological processes.

The evolutionarily conserved MOS4-associated complex

2011 ◽  
Vol 6 (5) ◽  
pp. 776-784 ◽  
Author(s):  
Kaeli Johnson ◽  
Oliver Dong ◽  
Xin Li
Keyword(s):  
Biological Function ◽  
Plant Immunity ◽  
Biological Processes ◽  
Future Studies ◽  
Time Control ◽  
Core Member ◽  
Evolutionarily Conserved ◽  
Core Components ◽  
Flowering Time Control ◽  
Insight Into

AbstractRecent work in plant immunity has shown that MOS4, a known intermediate in R protein mediated resistance, is a core member of the nuclear MOS4-associated complex (MAC). This complex is highly conserved in eukaryotes, as orthologous complexes known as the CDC5L-SNEVPrp19-Pso4 complex and the Nineteen complex (NTC) were previously identified in human and yeast, respectively. The involvement of these complexes in pre-mRNA splicing and spliceosome assembly suggests that the MAC probably has a similar function in plants. Double mutants of any two MAC components are lethal, whereas single mutants of the MAC core components mos4, Atcdc5, mac3, and prl1 are all viable and display pleiotropic defects. This suggests that while the MAC is required for some essential biological function such as splicing, individual MAC components are not crucial for complex functionality and likely have regulatory roles in other biological processes such as plant immunity and flowering time control. Future studies on MAC components in Arabidopsis will provide further insight into the regulatory mechanisms of the MAC on specific biological processes.

scholarly journals The i-Motif as a Molecular Target: More Than a Complementary DNA Secondary Structure

2021 ◽  
Vol 14 (2) ◽  
pp. 96
Author(s):  
Susie L. Brown ◽  
Samantha Kendrick
Keyword(s):  
Gene Expression ◽  
Secondary Structure ◽  
Biological Function ◽  
Molecular Target ◽  
Therapeutic Approaches ◽  
Promoter Regions ◽  
New Therapeutic Approaches ◽  
G Quadruplex ◽  
Dna Elements ◽  
Insight Into

Stretches of cytosine-rich DNA are capable of adopting a dynamic secondary structure, the i-motif. When within promoter regions, the i-motif has the potential to act as a molecular switch for controlling gene expression. However, i-motif structures in genomic areas of repetitive nucleotide sequences may play a role in facilitating or hindering expansion of these DNA elements. Despite research on the i-motif trailing behind the complementary G-quadruplex structure, recent discoveries including the identification of a specific i-motif antibody are pushing this field forward. This perspective reviews initial and current work characterizing the i-motif and providing insight into the biological function of this DNA structure, with a focus on how the i-motif can serve as a molecular target for developing new therapeutic approaches to modulate gene expression and extension of repetitive DNA.

scholarly journals NMR solution and X-ray crystal structures of a DNA molecule containing both right- and left-handed parallel-stranded G-quadruplexes

2019 ◽  
Vol 47 (15) ◽  
pp. 8272-8281 ◽  
Author(s):  
Fernaldo Richtia Winnerdy ◽  
Blaž Bakalar ◽  
Arijit Maity ◽  
J Jeya Vandana ◽  
Yves Mechulam ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Double Helix ◽  
Quadruple Helix ◽  
Single Nucleotide ◽  
Quadruplex Dna ◽  
Dna Structures ◽  
X Ray ◽  
Left Handed ◽  
G Quadruplex ◽  
Quadruplex Formation

AbstractAnalogous to the B- and Z-DNA structures in double-helix DNA, there exist both right- and left-handed quadruple-helix (G-quadruplex) DNA. Numerous conformations of right-handed and a few left-handed G-quadruplexes were previously observed, yet they were always identified separately. Here, we present the NMR solution and X-ray crystal structures of a right- and left-handed hybrid G-quadruplex. The structure reveals a stacking interaction between two G-quadruplex blocks with different helical orientations and displays features of both right- and left-handed G-quadruplexes. An analysis of loop mutations suggests that single-nucleotide loops are preferred or even required for the left-handed G-quadruplex formation. The discovery of a right- and left-handed hybrid G-quadruplex further expands the polymorphism of G-quadruplexes and is potentially useful in designing a left-to-right junction in G-quadruplex engineering.

scholarly journals A DNA structural alphabet provides new insight into DNA flexibility

2018 ◽  
Vol 74 (1) ◽  
pp. 52-64 ◽  
Author(s):  
Bohdan Schneider ◽  
Paulína Božíková ◽  
Iva Nečasová ◽  
Petr Čech ◽  
Daniel Svozil ◽  
...  
Keyword(s):  
Biological Function ◽  
Graphical Representation ◽  
Structural Alphabet ◽  
Dna Structures ◽  
Binding Partners ◽  
Validation Score ◽  
Fibre Diffraction ◽  
Interactive 3D ◽  
Automated Protocol ◽  
Insight Into

DNA is a structurally plastic molecule, and its biological function is enabled by adaptation to its binding partners. To identify the DNA structural polymorphisms that are possible in such adaptations, the dinucleotide structures of 60 000 DNA steps from sequentially nonredundant crystal structures were classified and an automated protocol assigning 44 distinct structural (conformational) classes called NtC (for Nucleotide Conformers) was developed. To further facilitate understanding of the DNA structure, the NtC were assembled into the DNA structural alphabet CANA (Conformational Alphabet of Nucleic Acids) and the projection of CANA onto the graphical representation of the molecular structure was proposed. The NtC classification was used to define a validation score called confal, which quantifies the conformity between an analyzed structure and the geometries of NtC. NtC and CANA assignment were applied to analyze the structural properties of typical DNA structures such as Dickerson–Drew dodecamers, guanine quadruplexes and structural models based on fibre diffraction. NtC, CANA and confal assignment, which is accessible at the website https://dnatco.org, allows the quantitative assessment and validation of DNA structures and their subsequent analysis by means of pseudo-sequence alignment. An animated Interactive 3D Complement (I3DC) is available in Proteopedia at http://proteopedia.org/w/Journal:Acta_Cryst_D:2.

scholarly journals Insight into the Complexity of the i-Motif and G-Quadruplex DNA Structures Formed in the KRAS Promoter and Subsequent Drug-Induced Gene Repression

2017 ◽  
Vol 139 (25) ◽  
pp. 8522-8536 ◽  
Author(s):  
Christine E. Kaiser ◽  
Natalie A. Van Ert ◽  
Prashansa Agrawal ◽  
Reena Chawla ◽  
Danzhou Yang ◽  
...  
Keyword(s):  
Gene Repression ◽  
Drug Induced ◽  
Quadruplex Dna ◽  
Dna Structures ◽  
G Quadruplex ◽  
Insight Into

An Insight into Oligopeptide Transporter 3 (OPT3) family proteins

2020 ◽  
Vol 27 ◽  
Author(s):  
Fırat Kurt
Keyword(s):  
Stress Responses ◽  
Chelating Agent ◽  
Biological Processes ◽  
Biotic And Abiotic Stress ◽  
Oligopeptide Transporter ◽  
Binding Residues ◽  
Fe Homeostasis ◽  
Proteins Interactions ◽  
Insight Into ◽  
Selection Of

: Oligopeptide transporter 3 (OPT3) proteins are one of the subsets of OPT clade, yet little is known about these transporters. Therefore, homolog OPT3 proteins in several plant species were investigated and characterized using bioinformatical tools. Motif and co-expression analyses showed that OPT3 proteins may be involved in both biotic and abiotic stress responses as well as growth and developmental processes. AtOPT3 usually seemed to take part in Fe homeostasis whereas ZmOPT3 putatively interacted with proteins involved in various biological processes from plant defense system to stress responses. Glutathione (GSH), as a putative alternative chelating agent, was used in the AtOPT3 and ZmOPT3 docking analyses to identify their putative binding residues. The information given in this study will contribute to the understanding of OPT3 proteins’ interactions in various pathways and to the selection of potential ligands for OPT3s.

scholarly journals DNA G-quadruplexes for native mass spectrometry in potassium: a database of validated structures in electrospray-compatible conditions

2021 ◽  
Author(s):  
Anirban Ghosh ◽  
Eric Largy ◽  
Valérie Gabelica
Keyword(s):  
Mass Spectrometry ◽  
Drug Targets ◽  
Native Mass Spectrometry ◽  
Drug Binding ◽  
Quadruplex Dna ◽  
Dna Structures ◽  
Nmr Structures ◽  
G Quadruplex ◽  
Screening Assays

Abstract G-quadruplex DNA structures have become attractive drug targets, and native mass spectrometry can provide detailed characterization of drug binding stoichiometry and affinity, potentially at high throughput. However, the G-quadruplex DNA polymorphism poses problems for interpreting ligand screening assays. In order to establish standardized MS-based screening assays, we studied 28 sequences with documented NMR structures in (usually ∼100 mM) potassium, and report here their circular dichroism (CD), melting temperature (Tm), NMR spectra and electrospray mass spectra in 1 mM KCl/100 mM trimethylammonium acetate. Based on these results, we make a short-list of sequences that adopt the same structure in the MS assay as reported by NMR, and provide recommendations on using them for MS-based assays. We also built an R-based open-source application to build and consult a database, wherein further sequences can be incorporated in the future. The application handles automatically most of the data processing, and allows generating custom figures and reports. The database is included in the g4dbr package (https://github.com/EricLarG4/g4dbr) and can be explored online (https://ericlarg4.github.io/G4_database.html).

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