Site selectivity of platinum anticancer therapeutics.
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.
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
D000970:Antineoplastic Agents; D018736:DNA Adducts; D006657:Histones; D009707:Nucleosomes; D010984:Platinum