1ddp

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Template:STRUCTURE 1ddp

SOLUTION STRUCTURE OF A CISPLATIN-INDUCED [CATAGCTATG]2 INTERSTRAND CROSS-LINK

Overview

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.

About this Structure

Full crystallographic information is available from OCA.

Reference

Solution structure of a cisplatin-induced DNA interstrand cross-link., Huang H, Zhu L, Reid BR, Drobny GP, Hopkins PB, Science. 1995 Dec 15;270(5243):1842-5. PMID:8525382 Page seeded by OCA on Fri May 2 13:44:08 2008