4XUJ

Nucleosome core particle containing adducts from treatment with a thiomorpholine-substituted [(eta-6-p-cymene)Ru(3-hydroxy-2-pyridone)Cl] compound

Summary for 4XUJ

• Entry DOI: 10.2210/pdb4xuj/pdb
• Descriptor: Histone H3.2, Histone H4, Histone H2A, ... (10 entities in total)
• Functional Keywords: nucleosome, ruthenium agent, dna-bindig protein-dna complex, dna-binding protein-dna complex, dna-binding protein/dna
• Biological source: Xenopus laevis (African clawed frog); More
• Cellular location: Nucleus: P84233 P62799 Q6AZJ8 P02281
• Total number of polymer chains: 10
• Total formula weight: 199153.51

Authors

Adhireksan, Z.,Davey, C.A. (deposition date: 2015-01-26, release date: 2016-01-27, Last modification date: 2025-08-20)

Primary citation

Hanif, M.,Meier, S.M.,Adhireksan, Z.,Henke, H.,Martic, S.,Movassaghi, S.,Labib, M.,Kandioller, W.,Jamieson, S.M.F.,Hejl, M.,Jakupec, M.A.,Kraatz, H.B.,Davey, C.A.,Keppler, B.K.,Hartinger, C.G.
Functionalization of Ruthenium(II)( eta 6 -p-cymene)(3-hydroxy-2-pyridone) Complexes with (Thio)Morpholine: Synthesis and Bioanalytical Studies.
Chempluschem, 82:841-847, 2017

PubMed Abstract: Hydroxypyr(id)ones constitute an emerging platform for the design of drug molecules, owing to their favorable biocompatibility and toxicity profiles. Herein, [Ru (η -p-cymene)] complexes with 3-hydroxy-2-pyridinone functionalized with morpholine and thiomorpholine, as a means often used in medicinal chemistry to alter the physicochemical properties of drug compounds, are reported. The compounds underwent hydrolysis of the Ru-Cl bond and the aqua species were stable for up to 48 h in aqueous solution, as observed by H NMR spectroscopy and ESI-MS. The compounds formed adducts with amino acids and proteins through cleavage of the pyridinone ligand. Binding experiments to the nucleosome core particle by means of X-ray crystallography revealed similar reactivity and exclusive binding to histidine moieties of the histone proteins. Preliminary cyclin-dependent kinase 2 (CDK2)/cyclin A kinase inhibitory studies revealed promising activity similar to that of structurally related organometallic compounds.

PubMed: 31961568
DOI: 10.1002/cplu.201700050

Experimental method

X-RAY DIFFRACTION (3.18 Å)