93del is a 16-nucleotide G-quadruplex-forming aptamer which can inhibit the activity of the HIV-1 integrase enzyme at nanomolar concentration. Previous structural analyses of 93del using NMR spectroscopy have shown that the aptamer forms an interlocked G-quadruplex structure in K solution. Due to its exceptional stability and unique topology, 93del has been used in many different studies involving DNA G-quadruplexes, such as DNA aptamer and multimer design, as well as DNA fluorescence research. To gain further insights on the structure of this unique aptamer, we have determined several high-resolution crystal structures of 93del and its variants. While confirming the overall dimeric interlocked G-quadruplex folding topology previously determined by NMR, our results reveal important detailed structural information, particularly the formation of a water-mediated A•G•G•G•G pentad. These insights allow us to better understand the formation of various structural elements in G-quadruplexes and should be useful for designing and manipulating G-quadruplex scaffolds with desired properties.
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http://dx.doi.org/10.1016/j.bbrc.2022.04.020 | DOI Listing |
Molecules
December 2024
State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry & Chemical Engineering and Center of Materials Analysis, Nanjing University, 163 Xianlin Avenue, Nanjing 210023, China.
G-quadruplex (G4), an important secondary structure of nucleic acids, is polymorphic in structure. G4 monomers can associate with each other to form multimers, which show better application performance than monomers in some aspects. G4 dimers, the simplest and most widespread multimeric structures, are often used as a representative for studying multimers.
View Article and Find Full Text PDFJ Am Chem Soc
September 2024
Laboratoire de Biologie et Pharmacologie Appliquée (LBPA), UMR8113 CNRS, ENS Paris-Saclay, Université Paris-Saclay, 4 Avenue des sciences, Gif-sur-Yvette 91190, France.
G-quadruplexes are noncanonical structures of nucleic acids formed mainly by G-rich sequences and play crucial roles in important cellular processes. They are also increasingly used in nanotechnology for their valuable properties. Various unexpected structures of G-quadruplexes have been solved recently, including a stable G-quadruplex lacking one guanine in the G-tetrad core, harboring a vacant site.
View Article and Find Full Text PDFInt J Biol Macromol
December 2023
ISBE-IT, University of Naples Federico II, Corso Umberto I, 80138 Naples, Italy; Department of Molecular Medicine and Medical Biotechnologies, University of Naples Federico II, Via Sergio Pansini 5, 80131 Naples, Italy.
G-wires are supramolecular DNA structures based on the G-quadruplex (G4) structural motif obtained by the self-assembly of interlocked slipped G-rich oligonucleotide (ON) strands, or by end-to-end stacking of G4 units. Despite the increasing interest towards G-wires due to their potential applications in DNA nanotechnologies, the self-assembly process to obtain G-wires having a predefined length and stability is still neither completely understood nor controlled. In our previous studies, we demonstrated that the d(5'CG-3'-3'-GC5') ON, characterized by the presence of a 3'-3'-inversion of polarity site self-assembles into a G-wire structure when annealed in the presence of K ions.
View Article and Find Full Text PDFBiochem Biophys Res Commun
July 2022
School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, 637371, Singapore; NTU Institute of Structural Biology, Nanyang Technological University, Singapore, 636921, Singapore. Electronic address:
93del is a 16-nucleotide G-quadruplex-forming aptamer which can inhibit the activity of the HIV-1 integrase enzyme at nanomolar concentration. Previous structural analyses of 93del using NMR spectroscopy have shown that the aptamer forms an interlocked G-quadruplex structure in K solution. Due to its exceptional stability and unique topology, 93del has been used in many different studies involving DNA G-quadruplexes, such as DNA aptamer and multimer design, as well as DNA fluorescence research.
View Article and Find Full Text PDFRSC Chem Biol
April 2021
Institute of Biochemistry, Universität Greifswald Felix-Hausdorff-Str. 4 D-17487 Greifswald Germany +49 3834 420-4427 +49 3834 420-4426.
Guanine(G)-rich DNA or RNA sequences can assemble or intramolecularly fold into G-quadruplexes formed through the stacking of planar G·G·G·G tetrads in the presence of monovalent cations. These secondary nucleic acid structures have convincingly been shown to also exist within a cellular environment exerting important regulatory functions in physiological processes. For identifying nucleic acid segments prone to quadruplex formation, a putative quadruplex sequence motif encompassing closely spaced tracts of three or more guanosines is frequently employed for bioinformatic search algorithms.
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