Antitumor Drug Nogalamycin Binds DNA in Both Grooves Simultaneously: Molecular Structure of Nogalamycin-DNA Complex

Yen Chywan Liaw, Yi Gui Gao, Howard Robinson, Gijs A. van der Marel, Jacques H. van Boom, Andrew H.J. Wang

Research output: Contribution to journalArticlepeer-review

104 Citations (Scopus)

Abstract

The three-dimensional molecular structures of the complexes between an interesting antitumor drug, nogalamycin, and two DNA hexamers, d[CGT(pS)ACG] and d[m5CGT(pS)Am5CG], were determined at high resolution by X-ray diffraction analyses. Two nogalamycins bind to the DNA double helix in a 2:1 ratio with the aglycon chromophore intercalated between the CpG steps at both ends of the helix. The nogalose and aminoglucose sugars lie in the minor and major grooves, respectively, of the distorted B-DNA double helix. The binding of nogalamycin to DNA requires that the base pairs in DNA open up transiently to allow the bulky sugars to go through. Specific hydrogen bonds are found in the complex between the drug and guanine bases. We suggest that nogalamycin may prefer GC sequences embedded in a stretch of AT sequences.

Original languageEnglish
Pages (from-to)9913-9918
Number of pages6
JournalBiochemistry
Volume28
Issue number26
DOIs
Publication statusPublished - 1989
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry

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