Book of Abstracts: Albany 2011
June 14-18 2011
©Adenine Press (2010)
A New Look at DNA Intercalation
Potential roles of intercalative binding have challenged researchers since Lerman’s discovery 50 years ago, with polarized light, that aromatic molecules may slide in between base-pairs. Also using polarized-light spectroscopy, combined with molecular modeling, we study DNA complexes with proteins as well as small molecules. Applied to human recombinase, Rad51, in its complex with dsDNA in solution, this approach resulted in a 3-D structure (1). In this and a corresponding prokaryotic recombinase complex in crystal (2) intercalation of hydrophobic residues is observed. This provides an explanation of a 50% elongation of DNA compared to double-helix pitch. Similarly, with ruthenium complexes [dppz(L) 2Ru] 2+ (L=phenanthroline or bipyridine), the dppz moiety intercalates and DNA undergoes significant local conformational changes, bases roll and tilt like in A-form DNA. Experimentally this is seen as a 10° roll of the dppz short axis. We notice additional effects that intercalation has on the DNA conformation, including a kink that the Δ (but not Λ) enantiomer of parental [phen3Ru] 2+ induces due to partial (“wedge”) intercalation of a phen-ring system, this DNA structure closely resembles the one observed in complex with a TATA-box binding protein.
Loop orientation and DNA binding. The modeled filament structure allows housing of a double-stranded DNA, as seen in side view. Both the L1 (magenta) and L2 (green) loops are facing the interior of the filament, available for interaction with DNA: Tyr-232 is intercalating between two DNA bases of one of the strands, and Arg-235 is located close to the sugar-phosphate backbone of the other DNA strand.
DNA bend upon “wedge” intercalation of [phen3Ru] 2+ the DNA helix axis exhibits a characteristic bend, also observed when TATA-box binding protein is in place.
Department of Chemistry and Biology