1MNV

Actinomycin D binding to ATGCTGCAT

1MNV の概要

• エントリーDOI: 10.2210/pdb1mnv/pdb
• 関連するPDBエントリー: 173D 1A7Y 1A7Z 1DSC 1DSD 1FJA 1I3W 1L1V 1OVF 1QFI 1UNJ 1UNM 209D 2D55 316D
• 関連するBIRD辞書のPRD_ID: PRD_000001
• 分子名称: 5'-D(*AP*TP*GP*CP*TP*GP*CP*AP*T)-3', ACTINOMYCIN D (3 entities in total)
• 機能のキーワード: actinomycin d, actinomycin, antibiotic, anti cancer, antitumor, chromophore, depsipeptide, dna-antibiotic complex, dna/antibiotic
• 由来する生物種: STREPTOMYCES ANTIBIOTICUS; 詳細
• タンパク質・核酸の鎖数: 4
• 化学式量合計: 8044.51

構造登録者

Hou, M.-H.,Robinson, H.,Gao, Y.-G.,Wang, A.H.-J. (登録日: 2002-09-06, 公開日: 2002-11-22, 最終更新日: 2024-10-30)

主引用文献

Hou, M.-H.,Robinson, H.,Gao, Y.-G.,Wang, A.H.-J.
Crystal Structure of Actinomycin D Bound to the Ctg Triplet Repeat Sequences Linked to Neurological Diseases
Nucleic Acids Res., 30:4910-, 2002

PubMed Abstract: 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.

PubMed: 12433994
DOI: 10.1093/NAR/GKF619

実験手法

X-RAY DIFFRACTION (2.6 Å)