1d17
From Proteopedia
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[[Image:1d17.gif|left|200px]] | [[Image:1d17.gif|left|200px]] | ||
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'''DNA-NOGALAMYCIN INTERACTIONS''' | '''DNA-NOGALAMYCIN INTERACTIONS''' | ||
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==About this Structure== | ==About this Structure== | ||
- | + | Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D17 OCA]. | |
==Reference== | ==Reference== | ||
DNA-nogalamycin interactions., Egli M, Williams LD, Frederick CA, Rich A, Biochemistry. 1991 Feb 5;30(5):1364-72. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/1991116 1991116] | DNA-nogalamycin interactions., Egli M, Williams LD, Frederick CA, Rich A, Biochemistry. 1991 Feb 5;30(5):1364-72. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/1991116 1991116] | ||
- | [[Category: Protein complex]] | ||
[[Category: Egli, M.]] | [[Category: Egli, M.]] | ||
[[Category: Frederick, C A.]] | [[Category: Frederick, C A.]] | ||
[[Category: Rich, A.]] | [[Category: Rich, A.]] | ||
[[Category: Williams, L D.]] | [[Category: Williams, L D.]] | ||
- | [[Category: | + | [[Category: Complexed with drug]] |
- | [[Category: | + | [[Category: Double helix]] |
- | [[Category: | + | [[Category: Modified]] |
- | [[Category: | + | [[Category: Right handed dna]] |
- | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May 2 13:20:03 2008'' | |
- | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + |
Revision as of 10:20, 2 May 2008
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
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 Fri May 2 13:20:03 2008