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Local mobility of nucleic acids as determined from crystallographic data:III. A daunomycin-DNA complex

Authors
Journal
Journal of Molecular Biology
0022-2836
Publisher
Elsevier
Publication Date
Volume
199
Issue
2
Identifiers
DOI: 10.1016/0022-2836(88)90318-x
Disciplines
  • Biology

Abstract

Abstract The local mobility of the complex between the anti-tumor drug daunomycin and a DNA hexanucleotide duplex of sequence d(CpGpTpApCpG) 2 has been determined by anisotropic refinement of single crystal X-ray diffraction data of 1·2 Å resolution (1 Å = 0·1 nm).The directions and amplitudes of the local motion indicate that changes in mobility of DNA due to daunomycin binding are primarily limited to the residues forming the intercalation site and do not propagate to the neighboring residues. The intercalated daunomycin ring system (aglycone) is rigidly fixed in the base stack, apparently serving as an anchor for the amino sugar segment of the drug which is one of the most mobile regions of the entire complex. The high flexibility of this amino sugar may be important for inhibition of replication and transcription not only by sterically blocking the minor groove, but also by allowing non-productive interactions to be formed with various polymerases or other DNA-binding proteins. The Crystallographic model is improved sufficiently by the rigid group anisotropic refinement to allow additional bound water molecules to be located.

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