Nucleic Acids Research, Vol 27, Issue 21 4261-4268, Copyright © 1999 by Oxford University Press
F Paquet, M Boudvillain, G Lancelot and M Leng
The DNA duplex d(CTCTCG*AGTCTC).d(GAGAC-TC*GAGAG) containing a single
trans- diammine-dichloroplatinum(II) interstrand cross-link (where G* and
C* represent the platinated bases) has been studied by two- dimensional
NMR. All the exchangeable and non-exchangeable proton resonance lines were
assigned (except H5'/H5") and the NOE intensities were transformed into
distances via the RELAZ program. By combining the NOESY and COSY data (330
constraints) and NMR-constrained molecular mechanics using JUMNA, a
solution structure of the cross-linked duplex has been determined. The
duplex is distorted over two base pairs on each side of the interstrand
cross-link and exhibits a slight bending of its axis ( approximately 20
degrees ) towards the minor groove. The platinated guanine G* adopts a syn
conformation. The rotation results in a Hoogsteen-type pairing between the
complementary G(6)* and C(19)* residues which is mediated by the platinum
moiety and is stabilized by a hydrogen bond between O6(G(6)*) and
N4H(C(19)*). The rise between the cross-linked residues and the adjacent
residues is increased owing to the interaction between these adjacent
residues and the ammine groups of the platinum moiety. These results are
discussed in relation to the slow rate of closure of the monofunctional
adducts into interstrand cross-links.
ARTICLES
NMR solution structure of a DNA dodecamer containing a transplatin interstrand GN7-CN3 cross-link
Centre de Biophysique Moleculaire, CNRS-UPR 4301, Rue Charles Sadron, F- 45071 Orleans Cedex 2, France. paquet@cnrs-orleans.fr
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