5DNN

Nucleosome core particle containing adducts of gold(I)-triethylphosphane and ruthenium(II)-toluene PTA complexes

5DNN の概要

• エントリーDOI: 10.2210/pdb5dnn/pdb
• 関連するPDBエントリー: 5DNM
• 分子名称: Histone H3.2, dichloro[(1,2,3,4,5,6-eta)-6-methylbenzene]1,3,5-triaza-7lambda~5~-phosphatricyclo[3.3.1.1~3,7~]dec-7-ylruthenium, Histone H4, ... (10 entities in total)
• 機能のキーワード: nucleosome, gold antitumour compound, ruthenium antitumour compound, histone binding, structural protein-dna complex, structural protein/dna
• 由来する生物種: Xenopus laevis (African clawed frog); 詳細
• 細胞内の位置: Nucleus: P84233 P62799 P02281
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 199920.43

構造登録者

Adhireksan, Z.,Ma, Z.,Davey, C.A. (登録日: 2015-09-10, 公開日: 2016-09-14, 最終更新日: 2023-11-08)

主引用文献

Adhireksan, Z.,Palermo, G.,Riedel, T.,Ma, Z.,Muhammad, R.,Rothlisberger, U.,Dyson, P.J.,Davey, C.A.
Allosteric cross-talk in chromatin can mediate drug-drug synergy
Nat Commun, 8:14860-14860, 2017

PubMed Abstract: Exploitation of drug-drug synergism and allostery could yield superior therapies by capitalizing on the immensely diverse, but highly specific, potential associated with the biological macromolecular landscape. Here we describe a drug-drug synergy mediated by allosteric cross-talk in chromatin, whereby the binding of one drug alters the activity of the second. We found two unrelated drugs, RAPTA-T and auranofin, that yield a synergistic activity in killing cancer cells, which coincides with a substantially greater number of chromatin adducts formed by one of the compounds when adducts from the other agent are also present. We show that this occurs through an allosteric mechanism within the nucleosome, whereby defined histone adducts of one drug promote reaction of the other drug at a distant, specific histone site. This opens up possibilities for epigenetic targeting and suggests that allosteric modulation in nucleosomes may have biological relevance and potential for therapeutic interventions.

PubMed: 28358030
DOI: 10.1038/ncomms14860

実験手法

X-RAY DIFFRACTION (2.8 Å)