1DDP: Solution Structure Of A Cisplatin-Induced [catagctatg]2 Interstrand Cross-Link

The widely used antitumor drug cis-diamminedichloroplatinum(II) (cisplatin or cis-DDP) reacts with DNA, cross-linking two purine residues through the N7 atoms, which reside in the major groove in B-form DNA. The solution structure of the short duplex [d(CAT-AGCTATG)]2 cross-linked at the GC:GC site was determined by nuclear magnetic resonance (NMR). The deoxyguanosine-bridging cis-diammineplatinum(II) lies in the minor groove, and the complementary deoxycytidines are extrahelical. The double helix is locally reversed to a left-handed form, and the helix is unwound and bent toward the minor groove. These findings were independently confirmed by results from a phase-sensitive gel electrophoresis bending assay. The NMR structure differs markedly from previously proposed models but accounts for the chemical reactivity, the unwinding, and the bending of cis-DDP interstrand cross-linked DNA and may be important in the formation and repair of these cross-links in chromatin.
PDB ID: 1DDPDownload
MMDB ID: 48636
PDB Deposition Date: 1995/10/26
Updated in MMDB: 2011/10
Experimental Method:
solution nmr
Source Organism:
Biological Unit for 1DDP: dimeric; determined by author
Molecular Components in 1DDP
Label Count Molecule
Nucleotide(1 molecule)
DNA (5'-d(*cp*ap*tp*ap*gp*cp*tp*ap*tp*g)-3')
Molecule annotation
Chemical (1 molecule)
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