Antitumor drug nogalamycin binds DNA in both grooves simultaneously: molecular structure of nogalamycin-DNA complex.
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.
Liaw
Y C
YC
Department of Physiology and Biophysics, University of Illinois at Urbana-Champaign 61801.
Gao
Y G
YG
Robinson
H
H
van der Marel
G A
GA
van Boom
J H
JH
Wang
A H
AH
D004247:DNA / Q000378:metabolism*; D003630:Daunorubicin / Q000031:analogs & derivatives* / Q000378:metabolism; D015394:Molecular Structure; D009621:Nogalamycin / Q000378:metabolism*; D009690:Nucleic Acid Conformation
D004247:DNA; D009621:Nogalamycin; D003630:Daunorubicin