1ovf
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NMR Structure of ActD/5'-CCGTTTTGTGG-3' Complex
OverviewOverview
Binding of actinomycin D (ActD) to the seemingly single-stranded DNA, (ssDNA) oligomer 5'-CCGTT3 GTGG-3' has been studied in solution using, high-resolution nuclear magnetic resonance (NMR) techniques. A strong, binding constant (8 x 10(6) M(-1)) and high quality NMR spectra have, allowed us to determine the initial DNA structure using distance geometry, as well as the final ActD-5'-CCGTT3 GTGG-3' complex structure using, constrained molecular dynamics calculations. The DNA oligomer, 5'-CCGTT3GTGG-3' in the complex forms a hairpin structure with tandem G.T, mismatches at the stem region next to a loop of three stacked thymine, bases pointing toward the major groove. Bipartite T2O-GH1 and T2O-G2NH2, hydrogen bonds were detected for the G.T mismatches that further stabilize, this unusual DNA hairpin. The phenoxazone chromophore of ActD intercalates, nicely between the tandem G.T mismatches in essentially one major, orientation. Additional hydrophobic interactions between the ActD quinoid, amino acid residues with the loop T5-T6-T7 backbone protons were also, observed. The hydrophobic G-phenoxazone-G interaction in the, ActD-5'-CCGTT3GTGG-3' complex is more robust than that of the classical, ActD- 5'-CCGCT3GCGG-3' complex, consistent with the roughly 2-fold, stronger binding of ActD to the 5'-CCGTT3GTGG-3' sequence than to its, 5'-CCG CT3GCGG-3' counterpart. Stabilization by ActD of a hairpin, containing non-canonical stem base pairs further strengthens the notion, that ActD or other related compounds may serve as a sequence- specific, ssDNA-binding agent that inhibits human immunodeficiency virus (HIV) and, other retroviruses replicating through ssDNA intermediates.
About this StructureAbout this Structure
1OVF is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
ReferenceReference
Solution structure of the ActD-5'-CCGTT3GTGG-3' complex: drug interaction with tandem G.T mismatches and hairpin loop backbone., Chin KH, Chen FM, Chou SH, Nucleic Acids Res. 2003 May 15;31(10):2622-9. PMID:12736312
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