Structural highlights
Publication Abstract from PubMed
cis-diamminedichloroplatinum (II) (cisplatin) is a powerful anti-tumor drug whose target is cellular DNA. In the reaction between DNA and cisplatin, covalent intrastrand and interstrand cross-links (ICL) are formed. Two solution structures of the ICL have been published recently. In both models the double-helix is bent and unwound but with significantly different angle values. We solved the crystal structure at 100K of a double-stranded DNA decamer containing a single cisplatin ICL, using the anomalous scattering (MAD) of platinum as a unique source of phase information. We found 47 degrees for double-helix bending and 70 degrees for unwinding in agreement with previous electrophoretic assays. The crystals are stabilized by intermolecular contacts involving two cytosines extruded from the double-helix, one of which makes a triplet with a terminal G.C pair. The platinum coordination is nearly square and the platinum residue is embedded into a cage of nine water molecules linked to the cross-linked guanines, to the two amine groups, and to the phosphodiester backbone through other water molecules. This water molecule organization is discussed in relation with the chemical stability of the ICL.
Crystal structure of a double-stranded DNA containing a cisplatin interstrand cross-link at 1.63 A resolution: hydration at the platinated site.,Coste F, Malinge JM, Serre L, Shepard W, Roth M, Leng M, Zelwer C Nucleic Acids Res. 1999 Apr 15;27(8):1837-46. PMID:10101191[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Coste F, Malinge JM, Serre L, Shepard W, Roth M, Leng M, Zelwer C. Crystal structure of a double-stranded DNA containing a cisplatin interstrand cross-link at 1.63 A resolution: hydration at the platinated site. Nucleic Acids Res. 1999 Apr 15;27(8):1837-46. PMID:10101191
