Specific interactions of distamycin with G‐quadruplex DNA

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...

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Bibliographic Details
Published in:Nucleic acids research 2003-06, Vol.31 (11), p.2944-2951
Main Authors: Cocco, Melanie J., Hanakahi, L. A., Huber, Michael D., Maizels, Nancy
Format: Article
Language:English
Subjects:
Base Sequence
Binding Sites
Binding, Competitive
Distamycins - chemistry
Distamycins - metabolism
DNA - chemistry
DNA - metabolism
G-Quadruplexes
Guanine - chemistry
Ligands
Models, Molecular
Nuclear Magnetic Resonance, Biomolecular
Nucleolin
Phosphoproteins - chemistry
Phosphoproteins - metabolism
Protein Binding
Protein Structure, Tertiary
Repetitive Sequences, Nucleic Acid
RNA-Binding Proteins - chemistry
RNA-Binding Proteins - metabolism
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Summary: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.
ISSN:0305-1048
1362-4962
1362-4962
DOI:10.1093/nar/gkg392