1a2e

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(New page: 200px<br /><applet load="1a2e" size="450" color="white" frame="true" align="right" spinBox="true" caption="1a2e, resolution 1.63&Aring;" /> '''CRYSTAL STRUCTURE OF...)
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Revision as of 20:11, 24 November 2007


1a2e, resolution 1.63Å

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CRYSTAL STRUCTURE OF A DOUBLE-STRANDED DNA DECAMER CONTAINING A CISPLATIN INTERSTRAND CROSS-LINK ADDUCT

Overview

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.

About this Structure

1A2E is a Protein complex structure of sequences from [1] with CPT as ligand. Full crystallographic information is available from OCA.

Reference

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

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