scholarly journals Intrastrand backbone-nucleobase interactions stabilize unwound right-handed helical structures of heteroduplexes of L-aTNA/RNA and SNA/RNA

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Yukiko Kamiya ◽  
Tadashi Satoh ◽  
Atsuji Kodama ◽  
Tatsuya Suzuki ◽  
Keiji Murayama ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Crystal Structures ◽  
Prebiotic Chemistry ◽  
Basic Research ◽  
Structural Features ◽  
Helical Structures ◽  
Base Pairs ◽  
Triplex Structure ◽  
Rna And Dna

Abstract Xeno nucleic acids, which are synthetic analogues of natural nucleic acids, have potential for use in nucleic acid drugs and as orthogonal genetic biopolymers and prebiotic precursors. Although few acyclic nucleic acids can stably bind to RNA and DNA, serinol nucleic acid (SNA) and L-threoninol nucleic acid (L-aTNA) stably bind to them. Here we disclose crystal structures of RNA hybridizing with SNA and with L-aTNA. The heteroduplexes show unwound right-handed helical structures. Unlike canonical A-type duplexes, the base pairs in the heteroduplexes align perpendicularly to the helical axes, and consequently helical pitches are large. The unwound helical structures originate from interactions between nucleobases and neighbouring backbones of L-aTNA and SNA through CH–O bonds. In addition, SNA and L-aTNA form a triplex structure via C:G*G parallel Hoogsteen interactions with RNA. The unique structural features of the RNA-recognizing mode of L-aTNA and SNA should prove useful in nanotechnology, biotechnology, and basic research into prebiotic chemistry.

scholarly journals The proto-Nucleic Acid Builder: a software tool for constructing nucleic acid analogs

2020 ◽  
Author(s):  
Asem Alenaizan ◽  
Joshua L Barnett ◽  
Nicholas V Hud ◽  
C David Sherrill ◽  
Anton S Petrov
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Rational Design ◽  
Chemical Space ◽  
Software Tool ◽  
Structural Features ◽  
Natural Polymers ◽  
Helical Structures ◽  
Dna And Rna ◽  
Nucleic Acid Analogs

Abstract The helical structures of DNA and RNA were originally revealed by experimental data. Likewise, the development of programs for modeling these natural polymers was guided by known structures. These nucleic acid polymers represent only two members of a potentially vast class of polymers with similar structural features, but that differ from DNA and RNA in the backbone or nucleobases. Xeno nucleic acids (XNAs) incorporate alternative backbones that affect the conformational, chemical, and thermodynamic properties of XNAs. Given the vast chemical space of possible XNAs, computational modeling of alternative nucleic acids can accelerate the search for plausible nucleic acid analogs and guide their rational design. Additionally, a tool for the modeling of nucleic acids could help reveal what nucleic acid polymers may have existed before RNA in the early evolution of life. To aid the development of novel XNA polymers and the search for possible pre-RNA candidates, this article presents the proto-Nucleic Acid Builder (https://github.com/GT-NucleicAcids/pnab), an open-source program for modeling nucleic acid analogs with alternative backbones and nucleobases. The torsion-driven conformation search procedure implemented here predicts structures with good accuracy compared to experimental structures, and correctly demonstrates the correlation between the helical structure and the backbone conformation in DNA and RNA.

scholarly journals Bat Red Blood Cells express Nucleic Acid Sensing Receptors and bind RNA and DNA

2022 ◽  
Author(s):  
LK Metthew Lam ◽  
Jane Dobkin ◽  
Kaitlyn A. Eckart ◽  
Ian Gereg ◽  
Andrew DiSalvo ◽  
...  
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Red Blood Cells ◽  
Immune Function ◽  
Blood Cells ◽  
Toll Like Receptors ◽  
Cpg Dna ◽  
Human Rbcs ◽  
Insight Into ◽  
Rna And Dna

Red blood cells (RBCs) demonstrate immunomodulatory capabilities through the expression of nucleic acid sensors. Little is known about bat RBCs, and no studies have examined the immune function of bat erythrocytes. Here we show that bat RBCs express the nucleic acid-sensing Toll-like receptors TLR7 and TLR9 and bind the nucleic acid ligands, single-stranded RNA, and CpG DNA. Collectively, these data suggest that, like human RBCs, bat erythrocytes possess immune function and may be reservoirs for nucleic acids. These findings provide unique insight into bat immunity and may uncover potential mechanisms by which virulent pathogens in humans are concealed in bats.

Helicase mechanisms and the coupling of helicases within macromolecular machines Part I: Structures and properties of isolated helicases

2002 ◽  
Vol 35 (4) ◽  
pp. 431-478 ◽  
Author(s):  
Emmanuelle Delagoutte ◽  
Peter H. von Hippel
Keyword(s):  
Crystal Structure ◽  
Nucleic Acid ◽  
Nucleic Acids ◽  
Binding Site ◽  
Crystal Structures ◽  
Base Pair ◽  
Biochemical Properties ◽  
Functional Coupling ◽  
Hexameric Helicases ◽  
Base Pair Opening

1. Mechanisms of nucleic acid (NA) unwinding by helicases 4322. Helicases may take advantage of ‘breathing’ fluctuations in dsNAs 4342.1 Stability and dynamics of dsNAs 4342.2 dsNAs ‘breathe’ in isolation 4352.3 Thermodynamics of terminal base pairs of dsNA 4382.4 Thermal fluctuations may be responsible for sequential base-pair opening at replication forks 4392.5 Helicases may capture single base-pair opening events sequentially 4403. Biochemical properties of helicases 4433.1 Binding of NAs 4433.2 Binding and hydrolysis of NTP 4453.3 Coordination between NA binding and NTP binding and hydrolysis activities 4464. Helicase structures and mechanistic consequences 4474.1 Amino-acid sequence analysis reveals conserved motifs that constitute the NTP-binding pocket and a portion of the NA-binding site 4474.2 Organization of hepatitis virus C NS3 RNA helicase 4494.2.1 Biochemical properties of HCV NS3 4494.2.2 Crystal structures of HCV NS3 helicase 4504.2.2.1 The apoprotein 4504.2.2.2 The protein–dU8 complex 4504.2.3 A possible unwinding mechanism 4524.2.4 What is the functional oligomeric state of HCV NS3? 4524.3 Organization of the PcrA helicase 4534.3.1 The apoenzyme and ADP–PcrA complex 4544.3.2 The protein–DNA–sulfate complex 4564.3.3 The PcrA–DNA–ADPNP complex 4564.3.4 A closer look at the NTP-binding site in the crystal structure of PcrA–ADPNP–DNA 4574.3.5 Communication between domains A and B 4574.3.6 How might ssDNA stimulate the ATPase activity of PcrA? 4574.3.7 A possible helicase translocation mechanism 4584.3.8 A possible unwinding mechanism 4584.4 Organization of the Rep helicase 4594.4.1 Biochemical properties 4594.4.2 Crystal structure of Rep bound to ssDNA 4624.5 Organization of the RecG helicase 4624.6 Hexameric helicases 4664.6.1 Insights from crystal structures of hexameric helicases 4674.6.2 Possible translocation and unwinding mechanisms 4685. Conclusions 4696. Acknowledgments 4727. References 472Helicases are proteins that harness the chemical free energy of ATP hydrolysis to catalyze the unwinding of double-stranded nucleic acids. These enzymes have been much studied in isolation, and here we review what is known about the mechanisms of the unwinding process. We begin by considering the thermally driven ‘breathing’ of double-stranded nucleic acids by themselves, in order to ask whether helicases might take advantage of some of these breathing modes. We next provide a brief summary of helicase mechanisms that have been elucidated by biochemical, thermodynamic, and kinetic studies, and then review in detail recent structural studies of helicases in isolation, in order to correlate structural findings with biophysical and biochemical results. We conclude that there are certainly common mechanistic themes for helicase function, but that different helicases have devised solutions to the nucleic acid unwinding problem that differ in structural detail. In Part II of this review (to be published in the next issue of this journal) we consider how these mechanisms are further modified to reflect the functional coupling of these proteins into macromolecular machines, and discuss the role of helicases in several central biological processes to illustrate how this coupling actually works in the various processes of gene expression.

scholarly journals The degradation of nucleic acids in, and the removal of breakdown products from the small intestines of steers

1980 ◽  
Vol 44 (1) ◽  
pp. 99-112 ◽  
Author(s):  
A. B. McAllan
Keyword(s):  
Uric Acid ◽  
Small Intestine ◽  
Polyethylene Glycol ◽  
Nucleic Acid ◽  
Nucleic Acids ◽  
Terminal Ileum ◽  
Pyrimidine Nucleosides ◽  
Small Intestines ◽  
Rna And Dna ◽  
Serum And Urine

1. Nucleic acids and breakdown products were estimated in digesta taken from different sites in the small intestines of slaughtered steers given different diets. Amounts passing different sites were compared using cellulose as a non-digestible marker. The validity of this marker was checked with chromic oxide in some experiments. In other experiments, nucleic acids or derivatives were infused into the proximal duodenum of steers receiving diets of approximately equal proportions of flaked maize and hay. The amounts disappearing during passage through the small intestine were estimated using polyethylene glycol (PEG) as a non- absorbable marker.2. In the slaughter experiments the amounts of nucleic acids entering the small intestine varied with the type of diet. RNA and DNA disappeared on average, to extents of 89% and 80% respectively between the abomasum and the terminal ileum, irrespective of the diet. RNA disappearance occurred almost entirely in the proximal quarter of the small intestine, whereas that of DNA extended further along the tract.3. Nucleic acid degradation in the upper small intestine was accompanied by the transient appearance of adenosine, guanosine and pyrimidine nucleosides. These products were in greatest concentration in digesta from the first quarter of the small intestine and had generally completely disappeared by the terminal ileum.4. Of the different substances infused into the small intestine, free nucleic acids were removed to extents greater than 97%, adenine, guanine and uracil had completely disappeared, thymine and xanthine to approximately 80% and 95% and hypoxanthine and cytosine to only 51% and 48% respectively. The nucleosides adenosine and cytidine were also completely removed in the small intestine but were replaced, in part, by the catabolic products inosine plus hypoxanthine or cytosine respectively. Other nucleosides were removed to approximately half the extent of the corresponding bases.5. Serum and urine allantoin and uric acid levels were related to the amounts of purines entering the small intestines in free or bound form.

Highly stable triple helix formation by homopyrimidine (l)-acyclic threoninol nucleic acids with single stranded DNA and RNA

2015 ◽  
Vol 13 (8) ◽  
pp. 2366-2374 ◽  
Author(s):  
Vipin Kumar ◽  
Venkitasamy Kesavan ◽  
Kurt V. Gothelf
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Triple Helix ◽  
Helical Structures ◽  
Single Stranded Dna ◽  
Dna And Rna ◽  
Helix Formation ◽  
Triple Helix Formation

Homopyrimidine acyclic (l)-threoninol nucleic acid (aTNA) was synthesized and found to form highly stable (l)-aTNA–DNA–(l)-aTNA and (l)-aTNA–RNA–(l)-aTNA triple helical structures.

scholarly journals Nucleic acid-based nanoengineering: novel structures for biomedical applications

2011 ◽  
Vol 1 (5) ◽  
pp. 702-724 ◽  
Author(s):  
Hanying Li ◽  
Thomas H. LaBean ◽  
Kam W. Leong
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Single Molecule ◽  
Biomedical Applications ◽  
Three Dimensional ◽  
Base Pairs ◽  
Single Molecule Level ◽  
Stimulus Responsive ◽  
Bioactive Agents ◽  
Novel Structures

Nanoengineering exploits the interactions of materials at the nanometre scale to create functional nanostructures. It relies on the precise organization of nanomaterials to achieve unique functionality. There are no interactions more elegant than those governing nucleic acids via Watson–Crick base-pairing rules. The infinite combinations of DNA/RNA base pairs and their remarkable molecular recognition capability can give rise to interesting nanostructures that are only limited by our imagination. Over the past years, creative assembly of nucleic acids has fashioned a plethora of two-dimensional and three-dimensional nanostructures with precisely controlled size, shape and spatial functionalization. These nanostructures have been precisely patterned with molecules, proteins and gold nanoparticles for the observation of chemical reactions at the single molecule level, activation of enzymatic cascade and novel modality of photonic detection, respectively. Recently, they have also been engineered to encapsulate and release bioactive agents in a stimulus-responsive manner for therapeutic applications. The future of nucleic acid-based nanoengineering is bright and exciting. In this review, we will discuss the strategies to control the assembly of nucleic acids and highlight the recent efforts to build functional nucleic acid nanodevices for nanomedicine.

scholarly journals Nucleic acid metabolism in the ruminant

1969 ◽  
Vol 23 (3) ◽  
pp. 671-682 ◽  
Author(s):  
A. B. Mcallan ◽  
R. H. Smith
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Acid Solution ◽  
Perchloric Acid ◽  
Trichloroacetic Acid ◽  
Acid Metabolism ◽  
Nucleic Acid Metabolism ◽  
Trichloroacetic Acid Solution ◽  
Rna And Dna

1. Procedures, based on those of Schmidt & Thannhauser (1945) and Schneider (1945), for the extraction and estimation of nucleic acids in bovine digesta were examined in detail.2. Final methods which were suitable for routine determination of RNA and DNA were essentially as follows. Digesta samples were extracted in the cold, first with a solution of trichloroacetic acid in ethanol, then with aqueous trichloroacetic acid solution and finally with lipid solvents. The dried residue was hydrolysed with alkali, purified by passage through a Dowex resin, and the RNA, in the form of mononucleotides, determined by U.V. absorption. DNA was determined separately in hot perchloric acid extracts of the original dried residue by colorimetric estimation of the deoxyribose content.

scholarly journals Recent progress in non-native nucleic acid modifications

2021 ◽  
Vol 50 (8) ◽  
pp. 5126-5164 ◽  
Author(s):  
Luke K. McKenzie ◽  
Roberto El-Khoury ◽  
James D. Thorpe ◽  
Masad J. Damha ◽  
Marcel Hollenstein
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Genetic Information ◽  
Recent Progress ◽  
Vast Array ◽  
Synthetic Accessibility ◽  
Rna And Dna

While Nature harnesses RNA and DNA to store, read and write genetic information, the inherent programmability, synthetic accessibility and wide functionality of these nucleic acids make them attractive tools for use in a vast array of applications.

scholarly journals Changes in nucleic acid and protein levels during in vitro germ¬nation and elongation of Lilium longifforum cv. "Ace" polleni

2014 ◽  
Vol 50 (1-2) ◽  
pp. 39-50
Author(s):  
William V. Dashek
Keyword(s):  
Nucleic Acid ◽  
Nucleic Acids ◽  
Total Protein ◽  
Time Course ◽  
Lilium Longiflorum ◽  
Protein Levels ◽  
Dna And Rna ◽  
Rna And Dna ◽  
Rna Levels

While changes in nucleic acid and protein levels during germination and subsequent tube elongation have been determined for a number of pollens, they have not been extensively examined for <em>in vitro</em> grown <em>Lilium longiflorum</em>, cv. `Ace' pollen. Nucleic acids and proteins were extracted with cold trichloroacetic acrid (TCA), cold-hot TCA or cold TCA and potassium hydroxide-perchloric acid (KOH-HClO<sub>4</sub>). Following extraction, RNA, DNA and total protein were assayed colorimetrically with orcinol, diphenylamine and Folin-Phenol reagents, respectively. Extraction of 500 x g supernatants with KOH-HClO<sub>4</sub>, yielded less RNA than either of the TCA-extraction procedures which gave similar nucleic acids and protein recoveries. Whereas total protein levels decreased initially and then increased during 36 h, RNA and DNA levels rose throughout the time-course. Precipitation and quaritiation of nucleic acids and protein from homogenized and soaicated 500 x g pellets resulted in time-dependent alterations in levels of macromolecules which differed from those for 500 x g supernatants. Whereas DNA and RNA levels increased and then decreased over 36 h, total protein levels remained constant for 12 h and then declined during the : next 24 h. Addition of the data obtained for 500 x g supernatants to those for 500 x g pellets revealed that total protein levels increased 2.4 times for the first 12 h and thereafter remained constant, that RNA levels increased 9.8 times for the first 12 h and then levelled off and that the DNA content rose more than 5 times over 36 h.

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