4kgc

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

spinqualitylabelsall models 4kgc, resolution 2.69Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 4kgc is a 10 chain structure with sequence from Xenopus laevis and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: X-ray diffraction, Resolution 2.69Å Ligands: HRU, MG, SO4 Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function H32_XENLA Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. Publication Abstract from PubMed 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 [(eta(6)-p-cymene)Ru(ethylene-diamine)Cl]PF6 and the relatively non-cytotoxic antimetastasis compound [(eta(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. Ligand substitutions between ruthenium-cymene compounds can control protein versus DNA targeting and anticancer activity.,Adhireksan Z, Davey GE, Campomanes P, Groessl M, Clavel CM, Yu H, Nazarov AA, Yeo CH, Ang WH, Droge P, Rothlisberger U, Dyson PJ, Davey CA Nat Commun. 2014 Mar 18;5:3462. doi: 10.1038/ncomms4462. PMID:24637564 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Histone 3D structures

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