1DDP

Solution structure of a CISPLATIN-INDUCED [CATAGCTATG]2 Interstrand cross-link

Summary for 1DDP

• Entry DOI: 10.2210/pdb1ddp/pdb
• Descriptor: DNA (5'-D(*CP*AP*TP*AP*GP*CP*TP*AP*TP*G)-3'), Cisplatin (2 entities in total)
• Functional Keywords: dna, double helix, antitumor drug, cis-ddp, interstrand cross-link
• Total number of polymer chains: 2
• Total formula weight: 6388.08

Authors

Zhu, L.,Huang, H.,Reid, B.R.,Drobny, G.P.,Hopkins, P.B. (deposition date: 1995-10-26, release date: 1996-03-08, Last modification date: 2024-03-13)

Primary citation

Huang, H.,Zhu, L.,Reid, B.R.,Drobny, G.P.,Hopkins, P.B.
Solution structure of a cisplatin-induced DNA interstrand cross-link.
Science, 270:1842-1845, 1995

PubMed Abstract: 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.

PubMed: 8525382

Experimental method

SOLUTION NMR