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1mnv

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{{STRUCTURE_1mnv| PDB=1mnv | SCENE= }}
{{STRUCTURE_1mnv| PDB=1mnv | SCENE= }}
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'''Actinomycin D binding to ATGCTGCAT'''
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===Actinomycin D binding to ATGCTGCAT===
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==Overview==
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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.
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{{ABSTRACT_PUBMED_12433994}}
==About this Structure==
==About this Structure==
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[[Category: Neurological disease]]
[[Category: Neurological disease]]
[[Category: X-ray diffraction]]
[[Category: X-ray diffraction]]
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Revision as of 21:30, 2 July 2008

Image:1mnv.png

Template:STRUCTURE 1mnv

Actinomycin D binding to ATGCTGCAT

Template:ABSTRACT PUBMED 12433994

About this Structure

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

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