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PDBsum entry 1a84
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References listed in PDB file
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Key reference
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Title
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Nmr solution structure of a DNA dodecamer duplex containing a cis-Diammineplatinum(ii) d(gpg) intrastrand cross-Link, The major adduct of the anticancer drug cisplatin.
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Authors
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A.Gelasco,
S.J.Lippard.
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Ref.
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Biochemistry, 1998,
37,
9230-9239.
[DOI no: ]
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PubMed id
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Abstract
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The structure of the DNA duplex dodecamer, d(CCTCTGGTCTCC. GGAGACCAGAGG),
containing the cisplatin d(GpG) 1,2-intrastrand cross-link at the position
denoted by asterisks, was determined in solution by high-resolution 2D NMR
spectroscopy and restrained molecular dynamics refinement. The
cis-[Pt(NH3)2¿d(GpG-N7(1), N7(2))¿] lesion causes the adjacent guanine bases
to roll toward one another by 49 degrees, leading to an overall helix bend angle
of 78 degrees. These features are more exaggerated than those observed in the
X-ray crystal structure determined for the same platinated duplex [Takahara et
al. (1995) Nature 377, 649-652]. A common property of the solution and crystal
structures is the widening and flattening of the minor groove opposite the
platinum adduct, affording geometric parameters resembling those found in A-form
DNA. This deformation is especially noteworthy for the solution structure
because its sugar puckers are primarily those of B-form DNA. The unwinding of
the helix at the site of platination is 25 degrees. The curvature and shape of
the platinated duplex are remarkably similar to those observed in DNA duplexes
complexed by the HMG-domain proteins SRY and LEF-1. The structure reveals how
cisplatin binding alters DNA in such a manner as to facilitate HMG-domain
protein recognition.
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Headers
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