Locating monovalent cations in the grooves of B-DNA

Here we demonstrate that monovalent cations can localize around B-DNA in ge ometrically regular, sequence-specific sites in oligonucleotide crystals. P ositions of monovalent ions were determined from high-resolution X-ray diff raction of DNA crystals grown in the presence of thallium(1) cations (T1(+) ). T1(+) has previously been shown to be a useful K+ mimic. T1(+) positions determined by refinement of model to data are consistent with positions de termined using isomorphous F-Tl - F-K difference Fouriers and anomalous dif ference Fouriers. None of the observed T1(+) sites surrounding CGCGAATTCGCG are fully occupied by Tl+ ions. The most highly occupied sites, located wi thin the G-tract major groove, have estimated occupancies ranging from 20% to 35%. The occupancies of the minor groove sites are estimated to be aroun d 10%. The T1(+) positions in general are not in direct proximity to phosph ate groups. The A-tract major groove appears devoid of localized cations. T he majority of the observed T1(+) ngaged in lattice interactions or crystal packing. The locations of the cation sites are dictated by coordination ge ometry, electronegative potential, avoidance of electropositive amino group s, and cation-pi interactions. It appears that partially dehydrated monoval ent cations, hydrated divalent cations, and polyamines compete for a common binding region on the floor of the G-tract major groove.