title: Structure of duplex DNA containing the cisplatin 1,2-{Pt(NH3)2}2+-d(GpG) cross-link at 1.77 A resolution.
abstract: We report the 1.77-A resolution X-ray crystal structure of a dodecamer DNA duplex with the sequence 5'-CCTCTGGTCTCC-3' that has been modified to contain a single engineered 1,2-cis-{Pt(NH(3))(2)}(2+)-d(GpG) cross-link, the major DNA adduct of cisplatin. These data represent a significant improvement in resolution over the previously published 2.6-A structure. The ammine ligands in this structure are clearly resolved, leading to improved visualization of the cross-link geometry with respect to both the platinum center and to the nucleobases, which adopt a higher energy conformation. Also better resolved are the deoxyribose sugar puckers, which allow us to re-examine the global structure of platinum-modified DNA. Another new feature of this model is the location of four octahedral [Mg(H(2)O)(6)](2+) ions associated with bases in the DNA major groove and the identification of 124 ordered water molecules that participate in hydrogen-bonding interactions with either the nucleic acid or the diammineplatinum(II) moiety.
authors.affiliation: Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, United States.
authors.forename: Ryan C
authors.initials: RC
authors.lastname: Todd
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lippard
mesh_terms: D002945:Cisplatin / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D008958:Models, Molecular; D009690:Nucleic Acid Conformation
chemical_list: D004247:DNA; D002945:Cisplatin