title: Mg2+ in the major groove modulates B-DNA structure and dynamics.
abstract: This study investigates the effect of Mg(2+) bound to the DNA major groove on DNA structure and dynamics. The analysis of a comprehensive dataset of B-DNA crystallographic structures shows that divalent cations are preferentially located in the DNA major groove where they interact with successive bases of (A/G)pG and the phosphate group of 5'-CpA or TpG. Based on this knowledge, molecular dynamics simulations were carried out on a DNA oligomer without or with Mg(2+) close to an ApG step. These simulations showed that the hydrated Mg(2+) forms a stable intra-strand cross-link between the two purines in solution. ApG generates an electrostatic potential in the major groove that is particularly attractive for cations; its intrinsic conformation is well-adapted to the formation of water-mediated hydrogen bonds with Mg(2+). The binding of Mg(2+) modulates the behavior of the 5'-neighboring step by increasing the BII (ε-ζ>0°) population of its phosphate group. Additional electrostatic interactions between the 5'-phosphate group and Mg(2+) strengthen both the DNA-cation binding and the BII character of the 5'-step. Cation binding in the major groove may therefore locally influence the DNA conformational landscape, suggesting a possible avenue for better understanding how strong DNA distortions can be stabilized in protein-DNA complexes.
authors: Dynamique des Structures et Interactions des Macromolécules Biologiques, UMR 665 INSERM-Université Paris Diderot, Sorbonne Paris Cité, Institut National de la Transfusion Sanguine, Paris, France.
authors: Marc
authors: M
authors: Guéroult
authors: Olivier
authors: O
authors: Boittin
authors: Oliver
authors: O
authors: Mauffret
authors: Catherine
authors: C
authors: Etchebest
authors: Brigitte
authors: B
authors: Hartmann
mesh_terms: D018360:Crystallography, X-Ray; D059371:DNA, B-Form / Q000737:chemistry* / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D056004:Molecular Dynamics Simulation; D009690:Nucleic Acid Conformation / Q000187:drug effects*; D009707:Nucleosomes / Q000187:drug effects / Q000378:metabolism; D055672:Static Electricity
chemical_list: D059371:DNA, B-Form; D009707:Nucleosomes; D008274:Magnesium