title: Site selectivity of platinum anticancer therapeutics.
abstract: X-ray crystallographic and biochemical investigation of the reaction of cisplatin and oxaliplatin with nucleosome core particle and naked DNA reveals that histone octamer association can modulate DNA platination. Adduct formation also occurs at specific histone methionine residues, which could serve as a nuclear platinum reservoir influencing adduct transfer to DNA. Our findings suggest that the nucleosome center may provide a favorable target for the design of improved platinum anticancer drugs.
authors.affiliation: Division of Structural and Computational Biology, School of Biological Sciences, Nanyang Technological University, 60 Nanyang Drive, Singapore 637551, Singapore.
authors.forename: Bin
authors.initials: B
authors.lastname: Wu
authors.forename: Peter
authors.initials: P
authors.lastname: Dröge
authors.forename: Curt A
authors.initials: CA
authors.lastname: Davey
mesh_terms: D000595:Amino Acid Sequence; D000970:Antineoplastic Agents / Q000737:chemistry*; D001483:Base Sequence; D018360:Crystallography, X-Ray; D018736:DNA Adducts / Q000737:chemistry; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009707:Nucleosomes / Q000737:chemistry / Q000378:metabolism; D010984:Platinum / Q000737:chemistry*; D017434:Protein Structure, Tertiary; D012680:Sensitivity and Specificity
chemical_list: D000970:Antineoplastic Agents; D018736:DNA Adducts; D006657:Histones; D009707:Nucleosomes; D010984:Platinum