Abstract
| - The topology of DNA quadruplexes depends on the nature and number of the nucleotides linkingG-quartet motifs. To assess the effects of a three-nucleotide TTT linker, the crystal structure of the DNAsequence d(G4T3G4) has been determined at 1.5 Å resolution, together with that of the brominated analogued(G4BrUTTG4) at 2.4 Å resolution. Both sequences form bimolecular intermolecular G-quadruplexes withlateral loops. d(G4BrUTTG4) crystallized in the monoclinic space group P21 with three quadruplex moleculesin the asymmetric unit, two associating together as a head-to-head stacked dimer, and the third as a singlehead-to-tail dimer. The head-to-head dimers have two lateral loops on the same G-quadruplex face andform an eight-G-quartet stack, with a linear array of seven K+ ions between the quartets. d(G4T3G4)crystallized in the orthorhombic space group C222 and has a structure very similar to the head-to-tail dimerin the P21 unit cell. The sequence studied here is able to form several different folds; however, all fourquadruplexes in the two structures have lateral loops, in contrast to the diagonal loops reported for theanalogous quadruplex with T4 loops. A total of seven independent T3 loops were observed in the twostructures. These can be classified into two discrete conformational classes, suggesting that these representpreferred loop conformations that are independent of crystal-packing forces.
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