Coiled-coil conformation of a pentamidine-DNA complex

Departament d'Enginyeria Química, Universitat Politècnica de Catalunya, E-08028 Barcelona, Spain.
Acta Crystallographica Section D Biological Crystallography (Impact Factor: 2.67). 03/2010; 66(Pt 3):251-7. DOI: 10.1107/S0907444909055693
Source: PubMed


The coiled-coil structure formed by the complex of the DNA duplex d(ATATATATAT)(2) with pentamidine is presented. The duplex was found to have a mixed structure containing Watson-Crick and Hoogsteen base pairs. The drug stabilizes the coiled coil through the formation of cross-links between neighbouring duplexes. The central part of the drug is found in the minor groove as expected, whereas the charged terminal amidine groups protrude and interact with phosphates from neighbouring molecules. The formation of cross-links may be related to the biological effects of pentamidine, which is used as an antiprotozoal agent in trypanosomiasis, leishmaniasis and pneumonias associated with AIDS. The DNA sequence that was used is highly abundant in most eukaryotic genomes. However, very few data are available on DNA sequences which only contain A.T base pairs.

10 Reads
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: If any proof were needed of DNA's versatile roles and use, it is certainly provided by the numerous depositions of new three-dimensional (3D) structures to the coordinate databanks (PDB, NDB) over the last two years. Quadruplex motifs involving G-repeats, adducted sequences and oligo-2'-deoxynucleotides (ODNs) with bound ligands are particularly well represented. In addition, structures of chemically modified DNAs (CNAs) and artificial analogs are yielding insight into stability, pairing properties, and dynamics, including those of the native nucleic acids. Besides being of significance for establishing diagnostic tools and in the analysis of protein-DNA interactions, chemical modification in conjunction with investigations of the structural consequences may yield novel nucleic acid-based therapeutics. DNA's predictable and highly specific pairing behavior makes it the material of choice for constructing 3D-nanostructures of defined architecture. Recently the first examples of DNA nanoparticle and self-assembled 3D-crystals were reported. Although the structures discussed in this review are all based either on X-ray crystallography or solution NMR, small angle X-ray scattering (SAXS), and cryoEM are proving to be useful approaches for the characterization of nanoscale DNA architecture.
    Preview · Article · Apr 2010 · Current Opinion in Structural Biology
  • [Show abstract] [Hide abstract]
    ABSTRACT: We present the structure of coiled coils found in two oligonucleotide DNA crystals. The sequences d(ATATATATAT) and d(CGATATATAT) are used. In the first case several coiled coils with different structures are found. In the second case a single structure is present. The results are compared with other coiled coil structures. They might be used in the development of new nanomaterials.
    No preview · Article · Oct 2010 · Industrial & Engineering Chemistry Research
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: There are general features of chromosome dynamics, such as homologue recognition in early meiosis, which are expected to involve related sequence motifs in non-coding DNA, with a similar distribution in different species. A search for such motifs is presented here. It has been carried out with the CONREPP programme. It has been found that short alternating AT sequences (10-20 bases) have a similar distribution in most eukaryotic organisms, with some exceptions related to unique meiotic features. All other microsatellite and repeat sequences vary significantly in different organisms. It is concluded that the unique structural features and uniform distribution of alternating AT sequences indicate that they may facilitate homologous chromosome pairing in the early preleptotene stage of meiosis. They may also play a role in the compaction of DNA in mitotic chromosomes.
    Preview · Article · May 2011 · Journal of Theoretical Biology
Show more