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PDBsum entry 1a2e
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References listed in PDB file
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Key reference
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Title
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Crystal structure of a double-Stranded DNA containing a cisplatin interstrand cross-Link at 1.63 a resolution: hydration at the platinated site.
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Authors
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F.Coste,
J.M.Malinge,
L.Serre,
W.Shepard,
M.Roth,
M.Leng,
C.Zelwer.
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Ref.
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Nucleic Acids Res, 1999,
27,
1837-1846.
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PubMed id
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Abstract
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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.
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Headers
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