1d17
From Proteopedia
|
DNA-NOGALAMYCIN INTERACTIONS
Overview
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.
About this Structure
1D17 is a Protein complex structure of sequences from [1] with NGM as ligand. Full crystallographic information is available from OCA.
Reference
DNA-nogalamycin interactions., Egli M, Williams LD, Frederick CA, Rich A, Biochemistry. 1991 Feb 5;30(5):1364-72. PMID:1991116
Page seeded by OCA on Sun Nov 25 02:14:03 2007
