scholarly journals Thrombin binding aptamer G-quadruplex stabilized by pyrene-modified nucleotides

2020 ◽  
Vol 48 (7) ◽  
pp. 3975-3986 ◽  
Author(s):  
Matic Kovačič ◽  
Peter Podbevšek ◽  
Hisae Tateishi-Karimata ◽  
Shuntaro Takahashi ◽  
Naoki Sugimoto ◽  
...  
Keyword(s):  
Structural Changes ◽  
3D Structure ◽  
Binding Affinities ◽  
Nmr Data ◽  
System Characterization ◽  
G Quadruplex ◽  
Modes Of Interaction ◽  
Exposed Surface Area ◽  
Uridine Nucleotides ◽  
Nuclease Degradation

Abstract Guanine-rich regions of the human genome can adopt non-canonical secondary structures. Their role in regulating gene expression has turned them into promising targets for therapeutic intervention. Ligands based on polyaromatic moieties are especially suitable for targeting G-quadruplexes utilizing their size complementarity to interact with the large exposed surface area of four guanine bases. A predictable way of (de)stabilizing specific G-quadruplex structures through efficient base stacking of polyaromatic functional groups could become a valuable tool in our therapeutic arsenal. We have investigated the effect of pyrene-modified uridine nucleotides incorporated at several positions of the thrombin binding aptamer (TBA) as a model system. Characterization using spectroscopic and biophysical methods provided important insights into modes of interaction between pyrene groups and the G-quadruplex core as well as (de)stabilization by enthalpic and entropic contributions. NMR data demonstrated that incorporation of pyrene group into G-rich oligonucleotide such as TBA may result in significant changes in 3D structure such as formation of novel dimeric topology. Site specific structural changes induced by stacking of the pyrene moiety on nearby nucleobases corelate with distinct thrombin binding affinities and increased resistance against nuclease degradation.

scholarly journals Structure and Stability of a Dimeric G-Quadruplex Formed by Cyclic Oligonucleotides

2010 ◽  
Vol 2010 ◽  
pp. 1-6 ◽  
Author(s):  
Joan Casals ◽  
Júlia Viladoms ◽  
Enrique Pedroso ◽  
Carlos González
Keyword(s):  
Telomeric Repeat ◽  
High Melting ◽  
Structure And Stability ◽  
Dimeric Structure ◽  
Nmr Data ◽  
High Melting Temperature ◽  
Sodium Nmr ◽  
G Quadruplex ◽  
Global Topology ◽  
Quadruplex Formation

We have studied the structure and stability of the cyclic dodecamer d<pGGGTTAGGGTTA>, containing two copies of the human telomeric repeat. In the presence of sodium, NMR data are consistent with a dimeric structure of the molecule in which two cycles self-associate forming a quadruplex with three guanine tetrads connected by edgewise loops. The two macrocycles are arranged in a parallel way, and the dimeric structure exhibits a high melting temperature. These results indicate that cyclization of the phosphodiester chain does not prevent quadruplex formation, although it affects the global topology of the quadruplex.

scholarly journals Исследование строения, ионной, молекулярной подвижности и термических свойств гидратов пентафторидоцирконата аммония

2019 ◽  
Vol 126 (2) ◽  
pp. 147
Author(s):  
Е.И. Войт ◽  
А.Б. Слободюк ◽  
Н.А. Диденко
Keyword(s):  
Structural Changes ◽  
Chemical Shifts ◽  
Molecular State ◽  
Structural Motif ◽  
Nmr Data ◽  
State Of Water ◽  
Hydrate Number ◽  
Bond Strengths ◽  
Isotropic Chemical Shifts ◽  
Ir And Raman

AbstractThe effect of hydrate number on the structural changes, thermal properties, and ionic (molecular) mobility character in NH_4ZrF_5 ⋅ H_2O, NH_4ZrF_5 ⋅ 0.75H_2O crystal hydrates have been investigated by the methods of IR, Raman, nuclear magnetic resonance (NMR) (^1H, ^19F, including ^19F MAS), and TG-DTA spectroscopy. Differences in crystal hydrate structures—anion structure, molecular state of water, and O–H⋅⋅⋅F, N–H⋅⋅⋅F hydrogen bond strengths—have been corroborated by IR and Raman spectroscopy data. Isotropic chemical shifts of magnetic inequivalent positions have been determined and attributed to crystal structures of the studied compounds by the method of ^19F MAS NMR. It has been established that the removal of water molecules from NH_4ZrF_5 ⋅ H_2O and NH_4ZrF_5 ⋅ 0.75H_2O results in the transformation of chain or layered structures accompanied by the increase of the number of bridge bonds while retaining or increasing the dimensionality of the anion structural motif. According to the ^1H NMR data, the NH $$_{4}^{ + }$$ cation diffusion in NH_4ZrF_5 occurs only in the temperature range of 370–520 K.

scholarly journals Chasing Particularities of Guanine- and Cytosine-Rich DNA Strands

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 434 ◽  
Author(s):  
Marko Trajkovski ◽  
Janez Plavec
Keyword(s):  
Structural Changes ◽  
Polyacrylamide Gel Electrophoresis ◽  
Dna Recombination ◽  
Cd Spectroscopy ◽  
G Quadruplex ◽  
Recombination Processes ◽  
Dna Strands ◽  
Native Polyacrylamide Gel Electrophoresis ◽  
Myc Gene

By substitution of natural nucleotides by their abasic analogs (i.e., 1′,2′-dideoxyribose phosphate residue) at critically chosen positions within 27-bp DNA constructs originating from the first intron of N-myc gene, we hindered hybridization within the guanine- and cytosine-rich central region and followed formation of non-canonical structures. The impeded hybridization between the complementary strands leads to time-dependent structural transformations of guanine-rich strand that are herein characterized with the use of solution-state NMR, CD spectroscopy, and native polyacrylamide gel electrophoresis. Moreover, the DNA structural changes involve transformation of intra- into inter-molecular G-quadruplex structures that are thermodynamically favored. Intriguingly, the transition occurs in the presence of complementary cytosine-rich strands highlighting the inability of Watson–Crick base-pairing to preclude the transformation between G-quadruplex structures that occurs via intertwining mechanism and corroborates a role of G-quadruplex structures in DNA recombination processes.

Inferring structural changes of hydroxylic solvents from NMR data

1988 ◽  
Vol 37 (3-4) ◽  
pp. 281-287 ◽  
Author(s):  
Piero Mirti ◽  
Vincenzo Zelano
Keyword(s):  
Structural Changes ◽  
Nmr Data

scholarly journals The predicted 3D structure of the human D2 dopamine receptor and the binding site and binding affinities for agonists and antagonists

2004 ◽  
Vol 101 (11) ◽  
pp. 3815-3820 ◽  
Author(s):  
M. Y. S. Kalani ◽  
N. Vaidehi ◽  
S. E. Hall ◽  
R. J. Trabanino ◽  
P. L. Freddolino ◽  
...  
Keyword(s):  
Binding Site ◽  
Dopamine Receptor ◽  
3D Structure ◽  
Binding Affinities ◽  
D2 Dopamine Receptor

scholarly journals Mechanistic Insights into the Effects of Key Mutations on SARS-CoV-2 RBD-ACE2 Binding

2021 ◽  
Author(s):  
Abhishek Aggarwal ◽  
Supriyo Naskar ◽  
Nikhil Maroli ◽  
Biswajit Gorai ◽  
Narendra M Dixit ◽  
...  
Keyword(s):  
Structural Changes ◽  
Underlying Mechanism ◽  
Free Energy Calculations ◽  
Target Cells ◽  
Original Strain ◽  
Binding Affinities ◽  
Receptor Binding Domain ◽  
Wild Type ◽  
Dynamics Simulations ◽  
Insight Into

Some recent SARS-CoV-2 variants appear to have increased transmissibility than the original strain. An underlying mechanism could be the improved ability of the variants to bind receptors on target cells and infect them. In this study, we provide atomic-level insight into the binding of the receptor binding domain (RBD) of the wild-type SARS-CoV-2 spike protein and its single (N501Y), double (E484Q, L452R) and triple (N501Y, E484Q, L452R) mutated variants to the human ACE2 receptor. Using extensive all-atom molecular dynamics simulations and advanced free energy calculations, we estimate the associated binding affinities and binding hotspots. We observe significant secondary structural changes in the RBD of the mutants, which lead to different binding affinities. We find higher binding affinities of the double (E484Q, L452R) and triple (N501Y, E484Q, L452R) mutated variants than the wild type and the N501Y variant, which could contribute to the higher transmissibility of recent variants containing these mutations.

scholarly journals Retinitis pigmentosa and molar tooth sign caused by novel AHI1 compound heterozygote pathogenic variants

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Chunyan Chen ◽  
Jiong Gao ◽  
Qing Lv ◽  
Chen Xu ◽  
Yu Xia ◽  
...  
Keyword(s):  
Structural Changes ◽  
Novel Mutation ◽  
3D Structure ◽  
Brain Magnetic Resonance Imaging ◽  
Chinese Patient ◽  
Molar Tooth ◽  
Compound Heterozygous ◽  
3D Protein Structure ◽  
Molar Tooth Sign ◽  
New Variant

Abstract Background Joubert syndrome (JS) is a group of rare congenital disorders characterized by cerebellar vermis dysplasia, developmental delay, and retina dysfunctions. Herein, we reported a Chinese patient carrying a new variant in the AHI1 gene with mild JS, and the 3D structure of the affected Jouberin protein was also predicted. Case presentation The patient was a 31-year-old male, who presented difficulty at finding toys at the age of 2 years, night blindness from age of 5 years, intention tremor and walking imbalance from 29 years of age. Tubular visual field and retina pigmentation were observed on ophthalmology examinations, as well as molar tooth sign on brain magnetic resonance imaging (MRI). Whole exome sequence revealed two compound heterozygous variants at c.2105C>T (p.T702M) and c.1330A>T (p.I444F) in AHI1 gene. The latter one was a novel mutation. The 3D protein structure was predicted using I-TASSER and PyMOL, showing structural changes from functional β-sheet and α-helix to non-functional D-loop, respectively. Conclusions Mild JS due to novel variants at T702M and I444F in the AHI1 gene was reported. The 3D-structural changes in Jouberin protein might underlie the pathogenesis of JS.

scholarly journals Moving toward generalizable NZ-1 labeling for 3D structure determination with optimized epitope-tag insertion

2021 ◽  
Vol 77 (5) ◽  
pp. 645-662
Author(s):  
Risako Tamura-Sakaguchi ◽  
Rie Aruga ◽  
Mika Hirose ◽  
Toru Ekimoto ◽  
Takuya Miyake ◽  
...  
Keyword(s):  
Complex Formation ◽  
Structure Determination ◽  
Structural Changes ◽  
Insertion Site ◽  
3D Structure ◽  
Binding Pocket ◽  
Crystallographic Analysis ◽  
Stable Complex ◽  
X Ray Crystallography ◽  
Dynamics Simulations

Antibody labeling has been conducted extensively for structure determination using both X-ray crystallography and electron microscopy (EM). However, establishing target-specific antibodies is a prerequisite for applying antibody-assisted structural analysis. To expand the applicability of this strategy, an alternative method has been developed to prepare an antibody complex by inserting an exogenous epitope into the target. It has already been demonstrated that the Fab of the NZ-1 monoclonal antibody can form a stable complex with a target containing a PA12 tag as an inserted epitope. Nevertheless, it was also found that complex formation through the inserted PA12 tag inevitably caused structural changes around the insertion site on the target. Here, an attempt was made to improve the tag-insertion method, and it was consequently discovered that an alternate tag (PA14) could replace various loops on the target without inducing large structural changes. Crystallographic analysis demonstrated that the inserted PA14 tag adopts a loop-like conformation with closed ends in the antigen-binding pocket of the NZ-1 Fab. Due to proximity of the termini in the bound conformation, the more optimal PA14 tag had only a minor impact on the target structure. In fact, the PA14 tag could also be inserted into a sterically hindered loop for labeling. Molecular-dynamics simulations also showed a rigid structure for the target regardless of PA14 insertion and complex formation with the NZ-1 Fab. Using this improved labeling technique, negative-stain EM was performed on a bacterial site-2 protease, which enabled an approximation of the domain arrangement based on the docking mode of the NZ-1 Fab.

Three new ZnII coordination polymers constructed from a semi-rigid tricarboxylic acid: structural changes caused by flexibility and luminescence sensing for hexavalent chromate anions

2019 ◽  
Vol 75 (9) ◽  
pp. 1286-1298 ◽  
Author(s):  
Yanyan An ◽  
Liping Lu ◽  
Miaoli Zhu
Keyword(s):  
Aqueous Solution ◽  
Hexavalent Chromium ◽  
Coordination Polymers ◽  
Structural Changes ◽  
Ph Value ◽  
Limit Of Detection ◽  
Weak Interactions ◽  
3D Structure ◽  
Tricarboxylic Acid ◽  
Hydrothermal Conditions

Coordination polymers (CPs) with specific structures and functional luminescence have been widely designed as sensors for detecting small molecules and ions. In this study, with or without the help of an N-donor auxiliary linker, three new ZnII CPs, namely, three-dimensional (3D) poly[[pentaaquabis[μ3-5-(4-carboxybenzyloxy)isophthalato]bis[μ6-5-(4-carboxylatobenzyloxy)isophthalato]di-μ3-hydroxido-hexazinc(II)] trihydrate], {[Zn6(C16H10O7)2(C16H9O7)2(OH)2(H2O)5]·3H2O} n or {[Zn6(μ3-HL)2(μ6-L)2(μ3-OH)2(H2O)5]·3H2O} n , (I), one-dimensional (1D) catena-poly[[[aqua(1,10-phenanthroline)zinc(II)]-μ2-5-(4-carboxybenzyloxy)isophthalato] dihydrate], {[Zn(C16H10O7)(C12H8N2)(H2O)]·2H2O} n or {[Zn(μ2-HL)(phen)(H2O)]·2H2O} n (phen is 1,10-phenanthroline), (II), and 3D poly[diaquatetrakis(4,4′-bipyridine)bis[μ6-5-(4-carboxylatobenzyloxy)isophthalato]di-μ3-formato-di-μ3-hydroxido-pentazinc(II)], [Zn5(C16H9O7)2(HCOO)2(OH)2(C10H8N2)4(H2O)2] n or [Zn5(μ4-L)2(bpy)4(μ2-OH)2(μ3-HCOO)2(H2O)2] n (bpy is 4,4′-bipyridine), (III), have been constructed from the semi-rigid tricarboxylic acid 5-(4-carboxybenzyloxy)isophthalic acid (H3 L) under hydrothermal conditions. CP (I) exhibits a twofold interpenetrated 3D+3D→3D skeleton with a 3,5-conn topology constructed from triangular trinuclear [Zn3(COO)4(μ3-OH)] clusters, in which the H3 L ligand adopts three different coordination modes. CP (II) exhibits a 1D infinite chain and stacking that gives a 3D structure mediated by hydrogen bonds and weak interactions. CP (III) is an interesting 3D 3,4,8-conn network including linear tetranuclear [Zn4(μ2-OH)2(HCOO)2(COO)2] clusters with a new {4·62}2{4·64·8}{46·619·83} topological symbol. The influences of the flexible –CH2–O– linker of the H3 L ligand and subtle environmental factors, such as solvent, pH value and auxiliary ligands, on the formation of the final structures are also discussed. The solid-state fluorescence spectra of CPs (I)–(III) were recorded at room temperature and all show better fluorescence performances than H3 L. In particular, (II) can act as a potential multifunctional fluorescent material for sensing hexavalent chromium ions in aqueous solution with high stability, selectivity and sensitivity. Under ultraviolet light of 365 nm from a UV lamp, a signal response of fluorescence from turning on to off can be observed with the naked eye. It was found that the detection for hexavalent chromium (i.e. Cr2O7 2−) by (II) has a high selectivity [K SV = 1.61 × 104 M −1 and limit of detection (LOD) = 0.434 µM] in aqueous solution. Quenching mechanisms were also studied in detail.

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