1mnv
From Proteopedia
|
Actinomycin D binding to ATGCTGCAT
Overview
The potent anticancer drug actinomycin D (ActD) acts by binding to DNA GpC, sequences, thereby interfering with essential biological processes, including replication, transcription and topoisomerase. Certain, neurological diseases are correlated with expansion of (CTG)n, trinucleotide sequences, which contain many contiguous GpC sites separated, by a single base pair. In order to characterize the binding of ActD to CTG, triplet repeat sequences, we carried out heat denaturation and CD, analyses, which showed that adjacent GpC sequences flanking a T:T mismatch, are preferred ActD-binding sites, and that ActD binding results in a, conformational transition to A-type structure. The structural basis of the, strong binding of ActD to neighboring GpC sites flanking a T:T mismatch, was provided by the crystal structure of ActD bound to ATGCTGCAT, which, contains a CTG triplet sequence. Binding of two ActD molecules to GCTGC, causes a kink in the DNA helix. In addition, using a synthetic, self-priming DNA model, 5'-(CAG)4(CTG)(16)-3', we observed that ActD can, trap the cruciform or duplexes of (CTG)n and interfere with the expansion, process of CTG triplet repeats as shown by gel electrophoretic expansion, assay. Our results may provide the possible biological consequence of ActD, bound to CTG triplet repeat sequences.
About this Structure
1MNV is a Protein complex structure of sequences from [1]. Full crystallographic information is available from OCA.
Reference
Crystal structure of actinomycin D bound to the CTG triplet repeat sequences linked to neurological diseases., Hou MH, Robinson H, Gao YG, Wang AH, Nucleic Acids Res. 2002 Nov 15;30(22):4910-7. PMID:12433994
Page seeded by OCA on Sun Nov 25 04:23:56 2007
