Light-Induced Formation of Thymine-Containing Mercury(II)-Mediated Base Pairs.
Ontology highlight
ABSTRACT:
SUBMITTER: Naskar S
PROVIDER: S-EPMC6972992 | biostudies-literature | 2019 Dec
REPOSITORIES: biostudies-literature
Publications
Light-Induced Formation of Thymine-Containing Mercury(II)-Mediated Base Pairs.
Naskar Shuvankar S Müller Jens J
Chemistry (Weinheim an der Bergstrasse, Germany) 20191119 71
By applying caged thymidine residues, DNA duplexes were created in which Hg<sup>II</sup> -mediated base pair formation can be triggered by irradiation with light. When a bidentate ligand was used as the complementary nucleobase, an unprecedented stepwise formation of different metal-mediated base pairs was achieved. ...[more]
Similar Datasets
Project description:We have determined the three-dimensional (3D) structure of DNA duplex that includes tandem Hg(II)-mediated T-T base pairs (thymine-Hg(II)-thymine, T-Hg(II)-T) with NMR spectroscopy in solution. This is the first 3D structure of metallo-DNA (covalently metallated DNA) composed exclusively of 'NATURAL' bases. The T-Hg(II)-T base pairs whose chemical structure was determined with the (15)N NMR spectroscopy were well accommodated in a B-form double helix, mimicking normal Watson-Crick base pairs. The Hg atoms aligned along DNA helical axis were shielded from the bulk water. The complete dehydration of Hg atoms inside DNA explained the positive reaction entropy (ΔS) for the T-Hg(II)-T base pair formation. The positive ΔS value arises owing to the Hg(II) dehydration, which was approved with the 3D structure. The 3D structure explained extraordinary affinity of thymine towards Hg(II) and revealed arrangement of T-Hg(II)-T base pairs in metallo-DNA.
| S-EPMC3973346 | biostudies-literature
Project description:Uracil DNA glycosylase (UNG) locates uracil and its structural congener thymine in the context of duplex DNA using a base flipping mechanism. NMR imino proton exchange measurements were performed on free and UNG-bound DNA duplexes in which a single thymine (T) was paired with a series of adenine analogues (X) capable of forming one, two, or three hydrogen bonds. The base pair opening equilibrium for the free DNA increased 55-fold as the number of hydrogen bonds decreased, but the opening rate constants were nearly the same in the absence and presence of UNG. In contrast, UNG was found to slow the base pair closing rate constants (kcl) compared to each free duplex by a factor of 3- to 23-fold. These findings indicate that regardless of the inherent thermodynamic stability of the TX pair, UNG does not alter the spontaneous opening rate. Instead, the enzyme holds the spontaneously expelled thymine (or uracil) in a transient extrahelical sieving site where it may partition forward into the enzyme active site (uracil) or back into the DNA base stack (thymine).
| S-EPMC2529456 | biostudies-literature
Project description:In nucleic acid chemistry, metal-mediated base pairs represent a versatile method for the site-specific introduction of metal-based functionality. In metal-mediated base pairs, the hydrogen bonds between complementary nucleobases are replaced by coordinate bonds to one or two transition metal ions located in the helical core. In recent years, the concept of metal-mediated base pairing has found a significant extension by applying it to parallel-stranded DNA duplexes. The antiparallel-stranded orientation of the complementary strands as found in natural B-DNA double helices enforces a cisoid orientation of the glycosidic bonds. To enable the formation of metal-mediated base pairs preferring a transoid orientation of the glycosidic bonds, parallel-stranded duplexes have been investigated. In many cases, such as the well-established cytosine-Ag(I)-cytosine base pair, metal complex formation is more stabilizing in parallel-stranded DNA than in antiparallel-stranded DNA. This review presents an overview of all metal-mediated base pairs reported as yet in parallel-stranded DNA, compares them with their counterparts in regular DNA (where available), and explains the experimental conditions used to stabilize the respective parallel-stranded duplexes.
| S-EPMC5753045 | biostudies-literature
Project description:The imidazole-Ag(I)-imidazole base pair is one of the best-investigated artificial metal-mediated base pairs. We show here that its stability can be further improved by formally replacing the imidazole moiety by a 2-methylimidazole or 4-methylimidazole moiety. A comparison of the thermal stability of several double helices shows that the addition of one equivalent of Ag(I) leads to a 50% larger increase in the melting temperature when a DNA duplex with methylated imidazole nucleosides is applied. This significant effect can likely be attributed to a better steric shielding of the metal ion within the metal-mediated base pair.
| S-EPMC4168905 | biostudies-literature
Project description:Metal-mediated base pairs involving artificial nucleobases have emerged as a promising means for the site-specific functionalization of nucleic acids with metal ions. In this context, a GNA-appended (GNA: glycol nucleic acid) nucleoside analogue containing the artificial nucleobase 1H-imidazo[4,5-f][1,10]phenanthroline (P) has already been applied successfully in a variety of homo- and heteroleptic metal-mediated base pairs, mainly involving Ag(I) ions. Herein, we report a thorough investigation of the Hg(II)-binding properties of P when incorporated into antiparallel-stranded DNA duplexes. The artificial nucleobase P is able to form Hg(II)-mediated homoleptic base pairs of the type P-Hg(II)-P with a [2?+?2] coordination environment. In addition, the heteroleptic P-Hg(II)-T pair was investigated. The addition of a stoichiometric amount of Hg(II) to a duplex comprising either a P:P pair or a P:T pair stabilizes the DNA duplex by 4.3 °C and 14.5 °C, respectively. The P-Hg(II)-T base pair, hence, represents the most stabilizing non-organometallic Hg(II)-mediated base pair reported to date. The formation of the Hg(II)-mediated base pairs was investigated by means of temperature-dependent UV spectroscopy and CD spectroscopy.
| S-EPMC7239801 | biostudies-literature
Project description:The dimerization of viral RNA through noncovalent interactions at their 5' ends is a key step in the life cycle of retroviruses. In Moloney murine leukemia virus, three stem-loops are important in this process. One is a self-complementary tetraloop (H1), but the other two stem-loops (H2, H3) contain highly conserved GACG tetraloops that are not self-complementary sequences. Using two-dimensional NMR, we determined the structure of the H3 stem-loop. Surprisingly, it forms a stable, homodimeric kissing complex through only two intermolecular G small middle dotC base pairs. Cross-strand interactions of the adenines adjacent to the intermolecular G small middle dotC base pairs, plus unusual strong electrostatic interactions around the base pairs, contribute to the unexpected stability. This structure shows how even stem-loops without self-complementary sequences can facilitate the intermolecular recognition between two identical RNAs, and thus initiate dimerization and encapsidation of retroviral RNAs.
| S-EPMC16875 | biostudies-literature
Project description:Base pairs involving post-transcriptionally modified nucleobases are believed to play important roles in a wide variety of functional RNAs. Here we present our attempts toward understanding the structural and functional role of naturally occurring modified base pairs using a combination of X-ray crystal structure database analysis, sequence analysis, and advanced quantum chemical methods. Our bioinformatics analysis reveals that despite their presence in all major secondary structural elements, modified base pairs are most prevalent in tRNA crystal structures and most commonly involve guanine or uridine modifications. Further, analysis of tRNA sequences reveals additional examples of modified base pairs at structurally conserved tRNA regions and highlights the conservation patterns of these base pairs in three domains of life. Comparison of structures and binding energies of modified base pairs with their unmodified counterparts, using quantum chemical methods, allowed us to classify the base modifications in terms of the nature of their electronic structure effects on base-pairing. Analysis of specific structural contexts of modified base pairs in RNA crystal structures revealed several interesting scenarios, including those at the tRNA:rRNA interface, antibiotic-binding sites on the ribosome, and the three-way junctions within tRNA. These scenarios, when analyzed in the context of available experimental data, allowed us to correlate the occurrence and strength of modified base pairs with their specific functional roles. Overall, our study highlights the structural importance of modified base pairs in RNA and points toward the need for greater appreciation of the role of modified bases and their interactions, in the context of many biological processes involving RNA.
| S-EPMC5435857 | biostudies-literature
Project description:The cis-syn thymine cyclobutane dimer is a DNA photoproduct implicated in skin cancer. We compared the stability of individual base pairs in thymine dimer-containing duplexes to undamaged parent 10-mer duplexes. UV melting thermodynamic measurements, CD spectroscopy, and 2D NOESY NMR spectroscopy confirm that the thymine dimer lesion is locally and moderately destabilizing within an overall B-form duplex conformation. We measured the rates of exchange of individual imino protons by NMR using magnetization transfer from water and determined the equilibrium constant for the opening of each base pair K(op). In the normal duplex K(op) decreases from the frayed ends of the duplex toward the center, such that the central TA pair is the most stable with a K(op) of 8 × 10??. In contrast, base pair opening at the 5'T of the thymine dimer is facile. The 5'T of the dimer has the largest equilibrium constant (K(op) = 3 × 10??) in its duplex, considerably larger than even the frayed penultimate base pairs. Notably, base pairing by the 3'T of the dimer is much more stable than by the 5'T, indicating that the predominant opening mechanism for the thymine dimer lesion is not likely to be flipping out into solution as a single unit. The dimer asymmetrically affects the stability of the duplex in its vicinity, destabilizing base pairing on its 5' side more than on the 3' side. The striking differences in base pair opening between parent and dimer duplexes occur independently of the duplex-single strand melting transitions.
| S-EPMC3912563 | biostudies-literature
Project description:A DNA fragment d(GCGAAAGCT), known to adopt a stable mini-hairpin structure in solution, has been crystallized in the space group I4(1)22 with the unit-cell dimensions a = b = 53.4 A and c = 54.0 A, and the crystal structure has been determined at 2.5 A resolution. The four nucleotide residues CGAA of the first half of the oligomer form a parallel duplex with another half through the homo base pairs, C2:C2+ (singly-protonated between the Watson- Crick sites), G3:G3 (between the minor groove sites), A4:A4 (between the major groove sites) and A5:A5 (between the Watson-Crick sites). The two strands remaining in the half of the parallel duplex are split away in different directions, and they pair in an anti-parallel B-form duplex with the second half extending from a neighboring parallel duplex, so that an infinite column is formed in a head-to-tail fashion along the c-axis. It seems that a hexa-ammine cobalt cation supports such a branched and bent conformation of the oligomer. One end of the parallel duplex is stacked on the corresponding end of the adjacent parallel duplex; between them, the guanine base of the first residue is stacked on the fourth ribose of another duplex.
| S-EPMC137954 | biostudies-literature
Project description:Graphene quantum dots (GQDs) were connected to [Ru(bpy)3]2+ to sense DNA-mediated charge transfer. Interaction between abasic site double stranded DNA (Abasic-DNA) and [Ru(bpy)3-GQD]2+ was investigated by absorption spectroscopy, gel electrophoresis, circular dichroism, and melting temperature measurements. The results indicate that [Ru(bpy)3-GQD]2+ could be intercalated into double stranded DNA. Using [Ru(bpy)3-GQD]2+ as a signal molecule, the charge transfer performance of DNA-intercalated [Ru(bpy)3-GQD]2+ was determined using electrochemical and electrochemiluminescence measurements. Various DNA types were immobilized on Au electrodes via Au-S bonds. Electrochemiluminescence and electrochemical measurements indicate that [Ru(bpy)3-GQD]2+ could enhance DNA-mediated charge transfer when intercalated into an abasic site of double stranded DNA. And comparing with [Ru(bpy)3]2+, it can be concluded that GQDs intercalate into the DNA duplex by acting as a base analog, thus enhancing DNA charge transfer. These findings suggest that the DNA-GQD structure could aid the development of molecular devices and electric drivers, and broaden the application of DNA charge transfer.
| S-EPMC9072722 | biostudies-literature