title: Specific interactions of distamycin with G-quadruplex DNA.
abstract: Distamycin binds the minor groove of duplex DNA at AT-rich regions and has been a valuable probe of protein interactions with double-stranded DNA. We find that distamycin can also inhibit protein interactions with G-quadruplex (G4) DNA, a stable four-stranded structure in which the repeating unit is a G-quartet. Using NMR, we show that distamycin binds specifically to G4 DNA, stacking on the terminal G-quartets and contacting the flanking bases. These results demonstrate the utility of distamycin as a probe of G4 DNA-protein interactions and show that there are (at least) two distinct modes of protein-G4 DNA recognition which can be distinguished by sensitivity to distamycin.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT 06520, USA. cocco@csb.yale.edu
authors.forename: Melanie J
authors.initials: MJ
authors.lastname: Cocco
authors.forename: L A
authors.initials: LA
authors.lastname: Hanakahi
authors.forename: Michael D
authors.initials: MD
authors.lastname: Huber
authors.forename: Nancy
authors.initials: N
authors.lastname: Maizels
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D001667:Binding, Competitive; D004247:DNA / Q000737:chemistry* / Q000378:metabolism*; D004214:Distamycins / Q000737:chemistry* / Q000378:metabolism*; D054856:G-Quadruplexes; D006147:Guanine / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D010750:Phosphoproteins / Q000737:chemistry / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D016601:RNA-Binding Proteins / Q000737:chemistry / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D000097796:Nucleolin
chemical_list: D004247:DNA; D004214:Distamycins; D006147:Guanine; D008024:Ligands; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D000097796:Nucleolin; C030000:stallimycin