4KGC

Nucleosome Core Particle Containing (ETA6-P-CYMENE)-(1, 2-ETHYLENEDIAMINE)-RUTHENIUM

4KGC の概要

• エントリーDOI: 10.2210/pdb4kgc/pdb
• 分子名称: Histone H3.2, Histone H4, Histone H2A, ... (9 entities in total)
• 機能のキーワード: dna-protein complex, nucleosome, ruthenium agents, structural protein-dna complex, structural protein/dna
• 由来する生物種: Xenopus laevis (clawed frog,common platanna,platanna); 詳細
• 細胞内の位置: Nucleus: P84233 P62799 P02281; Chromosome . Nucleus : Q6AZJ8
• タンパク質・核酸の鎖数: 10
• 化学式量合計: 200792.86

構造登録者

Adhireksan, Z.,Davey, C.A. (登録日: 2013-04-29, 公開日: 2014-03-26, 最終更新日: 2024-03-20)

主引用文献

Adhireksan, Z.,Davey, G.E.,Campomanes, P.,Groessl, M.,Clavel, C.M.,Yu, H.,Nazarov, A.A.,Yeo, C.H.,Ang, W.H.,Droge, P.,Rothlisberger, U.,Dyson, P.J.,Davey, C.A.
Ligand substitutions between ruthenium-cymene compounds can control protein versus DNA targeting and anticancer activity
Nat Commun, 5:3462-3462, 2014

PubMed Abstract: Ruthenium compounds have become promising alternatives to platinum drugs by displaying specific activities against different cancers and favourable toxicity and clearance properties. Nonetheless, their molecular targeting and mechanism of action are poorly understood. Here we study two prototypical ruthenium-arene agents-the cytotoxic antiprimary tumour compound [(η(6)-p-cymene)Ru(ethylene-diamine)Cl]PF6 and the relatively non-cytotoxic antimetastasis compound [(η(6)-p-cymene)Ru(1,3,5-triaza-7-phosphaadamantane)Cl2]-and discover that the former targets the DNA of chromatin, while the latter preferentially forms adducts on the histone proteins. Using a novel 'atom-to-cell' approach, we establish the basis for the surprisingly site-selective adduct formation behaviour and distinct cellular impact of these two chemically similar anticancer agents, which suggests that the cytotoxic effects arise largely from DNA lesions, whereas the protein adducts may be linked to the other therapeutic activities. Our study shows promise for developing new ruthenium drugs, via ligand-based modulation of DNA versus protein binding and thus cytotoxic potential, to target distinguishing epigenetic features of cancer cells.

PubMed: 24637564
DOI: 10.1038/ncomms4462

実験手法

X-RAY DIFFRACTION (2.69 Å)