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

Stephen R. Holbrook, Andrew H.J. Wang, Alexander Rich, Sung Hou Kim

研究成果: 雜誌貢獻文章同行評審

22 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)349-357
頁數9
期刊Journal of Molecular Biology
199
發行號2
DOIs
出版狀態已發佈 - 1月 20 1988
對外發佈

ASJC Scopus subject areas

  • 結構生物學
  • 分子生物學

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