Crystal Structures of Oligonucleotides

DNA is not the perfect double helix of traditional textbooks. Slight, but significant structiu e variations have been demonstrated from comparison of crystal structures of oligonucleotides. It has also become evident that these structure variations are not entirely determined by the individual base-steps (AA, AT, GC, etc), but are influenced by sequence contexts (1,2). The emerging picture of the DNA duplex, in fact, suggests a dynamic structure that is continuously contorted in a sequence-dependent manner. 

The spatial arrangement of solute heavy atoms of biological molecules is available from a wide variety of sources, especially those from X-ray crystallography. The Brookhaven Protein Data Bank (PDB) contains over 600 sets of coordinates for proteins, and NDB contains over 200 crystal structures of oligonucleotides. X-ray crystal structures of protein—DNA complexes are also available from both sources. Increasingly, solution structures of DNA and protein, solved by NMR spectroscopy, are becoming available. Structures of canonical DNA can also be derived by means of fiber diffraction data. ... 

In 1994 and 1995, two crystal structures of hammerhead ribozymes [31,32] and a structural analysis based on fluorescence resonance energy transfer studies [41] were published. In case of the crystal structure analyses, both ribozyme variants contained certain modifications that had been introduced to avoid self-cleavage [31,32]. In one case a DNA-analog of the substrate oligonucleotide was used [31], in the other case the all-RNA substrate contained a I -O-CR modification at the attacking 2 -OH group to avoid cleavage in the crystal [32] for reviews see [8,42,43]. 

In an oligonucleotide-drug hydrate complex, the appearance of a clathrate hydrate-like water structure prompt a molecular dynamics simulation (40). Again the results were only partially successful, prompting the statement, "The predictive value of simulation for use in analysis and interpretation of crystal hydrates remains to be established." However, recent molecular dynamics calculations have been more successful in simulating the water structure in Ae host lattice of a-cyclodextrin and P-cyclodextrin in the crystal structures of these hydrates (41.42). 

Vicens, Q. Westhof, E. Crystal structure of a complex between the aminoglycoside tobramycin and an oligonucleotide containing the ribosomal decoding a site. Chem. Biol. 2002, 9, 747-755. 

Vicens, Q. and Westhof, E. (2003). Crystal structure of geneticin bound to a bacterial 16S ribosomal RNA A site oligonucleotide. /. Mol. Biol. 326,1175-1188. 

Detailed studies of the structures (including crystal structures) of the formed adducts of cisplatin with oligonucleotides and DNA (again from several sources). 

Figure 2.37 Two views of the crystal structure of [Rh(R, R-Me2trien) (phi)]3+ bound within an eight-base-pair oligonucleotide. (Reproduced with permission from [18] 1999, American Chemical Society).

TnpA behaves as a dimer in solution and a crystal structure indicated that the molecule forms an elongated and flat dimer (8). The crystal structure of the complex formed by TnpA and a 22 nt long, single-stranded oligonucleotide that represents the RE palindrome showed a DNA hairpin (an imperfect palindrome) bound to each of the two recognition sites in the TnpA dimer (8). 

The crystal structures of 9-substituted adenines confirm the 6-amino structure. Specific stacking patterns are found in crystals of purine derivatives which are also observed for nucleosides, mono- and oligonucleotides. For X-ray results on tautomerism see Table 2 (p 309). Other sources of X-ray data are given in Table 6. 

A number of oligonucleotide hairpin, quadruplexes and other higher ordered tertiary structures have also been reported the solution structure of the transcriptional antiterminator LicT from Bacillus subtilis bound to a 29 bp ribonucleic antiterminator RNA hairpin " a crystal structure of a kissing complex of the HIV-1 RNA dimerisation initiation site " the crystal structure of the Za high affinity-binding domain of the RNA editing enzyme ADARl bound to left-handed Z-DNA " the crystal structure of parallel quadruplexes from human telomeric DNA. " ... 

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