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PDBsum entry 1n4b
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References listed in PDB file
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Key reference
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Title
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Solution structure of a DNA duplex containing mispair-Aligned n4c-Ethyl-N4c interstrand cross-Linked cytosines.
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Authors
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M.Webba da silva,
A.M.Noronha,
D.M.Noll,
P.S.Miller,
O.M.Colvin,
M.P.Gamcsik.
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Ref.
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Biochemistry, 2002,
41,
15181-15188.
[DOI no: ]
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PubMed id
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Abstract
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The solution structure of an interstrand cross-linked self-complementary
oligodeoxynucleotide containing directly opposed alkylated N(4)C-ethyl-N(4)C
cytosine bases was determined by molecular dynamics calculations guided by
NMR-derived restraints. The undecamer d(CGAAACTTTCG)(2), where C represents
directly opposed alkylated N(4)C-ethyl-N(4)C cytosine bases, serves as model for
the cytotoxic cross-links formed by bifunctional alkylating agents used in
cancer therapy. The structure of the duplex shows the cross-link protruding into
the major groove. An increase in the diameter of the DNA at the pseudoplatform
formed by the cross-linked residues creates an A-DNA characteristic hole in the
central portion of the DNA. This results in a centrally underwound base step and
a number of subsequent overwinding steps leading to an overall axis bend toward
the major groove. The structure shows narrowing of both minor and major grooves
in the proximity of the cross-link. The perturbation leads to preferential
intrastrand base stacking, disruption of adjacent canonical (A.T) base pairing,
and buckling of base pairs, the extent of which diminishes with progression away
from the lesion site. Overall, the distortion induced by the cross-link spreads
over three base pairs on the 5'- and 3'-sides of the cross-link.
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Headers
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