1D17

DNA-NOGALAMYCIN INTERACTIONS

1D17 の概要

• エントリーDOI: 10.2210/pdb1d17/pdb
• 分子名称: DNA (5'-D(*(5CM)P*GP*TP*AP*(5CM)P*G)-3'), NOGALAMYCIN (3 entities in total)
• 機能のキーワード: right handed dna, double helix, complexed with drug, modified, dna
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 2625.07

構造登録者

Egli, M.,Williams, L.D.,Frederick, C.A.,Rich, A. (登録日: 1990-08-08, 公開日: 1991-07-15, 最終更新日: 2024-02-07)

主引用文献

Egli, M.,Williams, L.D.,Frederick, C.A.,Rich, A.
DNA-nogalamycin interactions.
Biochemistry, 30:1364-1372, 1991

PubMed Abstract: The anthracycline antibiotic nogalamycin differs from the more common daunomycin-type anthracyclines by substitution on both ends of the intercalating chromophore, giving nogalamycin the approximate shape of a dumbbell. The chromophore of daunomycin is substituted on only one end. In nogalamycin, the positively charged amino sugar substituent of daunomycin is replaced by an uncharged nogalose sugar and a methyl ester group. The other end of nogalamycin, where daunomycin is unsubstituted, is fused to a bicyclo amino sugar with a positively charged dimethylamino group. Much larger DNA fluctuations are required for intercalative entry of nogalamycin than for entry of daunomycin. This report describes the X-ray crystal structure of the complex between nogalamycin and the self-complementary DNA hexamer d(me5CGTsAme5CG). The DNA contains cytosines methylated at the 5-positions and a phosphorothioate linkage at the TpA step. Nogalamycin intercalates at the terminal CpG steps and interacts with both strands in both grooves of the DNA. Large conformational adjustments in both nogalamycin and the DNA are necessary to form a stable, intercalative complex. The interactions of the bases with the nogalamycin substituents lead to sliding of bases relative to each other along the normal to Watson-Crick hydrogen bonds. The planarities of base pairs surrounding the intercalation site are distorted. The backbones of the two strands are distorted asymmetrically by nogalamycin with large deviations from standard B-DNA geometry. The complex between nogalamycin and DNA illustrates the conformational flexibility of DNA. The hydrogen-bonding interactions between nogalamycin and DNA do not suggest a sequence-specific binding of the drug, although additional secondary effects might lead to differences between various intercalation sites.

PubMed: 1991116
DOI: 10.1021/bi00219a029

実験手法

X-RAY DIFFRACTION (2 Å)