1A2E: Crystal Structure Of A Double-Stranded Dna Decamer Containing A Cisplatin Interstrand Cross-Link Adduct

Citation:
Abstract
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.
PDB ID: 1A2EDownload
MMDB ID: 47723
PDB Deposition Date: 1998/1/5
Updated in MMDB: 2012/11
Experimental Method:
x-ray diffraction
Resolution: 1.63  Å
Source Organism:
Biological Unit for 1A2E: dimeric; determined by author
Molecular Components in 1A2E
Label Count Molecule
Nucleotides(2 molecules)
1
DNA (5'-d(*cp*cp*tp*cp*gp*cp*tp*cp*tp*c)-3')
Molecule annotation
1
DNA (5'-d(*gp*ap*gp*ap*gp*cp*gp*ap*gp*g)-3')
Molecule annotation
Chemical (1 molecule)
1
1
* Click molecule labels to explore molecular sequence information.

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