Structure of duplex DNA containing the cisplatin 1,2-{Pt(NH3)2}[superscript 2]+-d(GpG) crosslink at 1.77 [Angstrom] resolution

Abstract

We report the 1.77-Å 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(NH3)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-Å 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(H2O)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.