1d10: Difference between revisions

Revision as of 13:19, 2 May 2008

STRUCTURAL COMPARISON OF ANTICANCER DRUG-DNA COMPLEXES. ADRIAMYCIN AND DAUNOMYCIN

OverviewOverview

The anticancer drugs adriamycin and daunomycin have each been crystallized with the DNA sequence d(CGATCG) and the three-dimensional structures of the complexes solved at 1.7- and 1.5-A resolution, respectively. These antitumor drugs have significantly different clinical properties, yet they differ chemically by only the additional hydroxyl at C14 of adriamycin. In these complexes the chromophore is intercalated at the CpG steps at either end of the DNA helix with the amino sugar extended into the minor groove. Solution of the structure of daunomycin bound to d(CGATCG) has made it possible to compare it with the previously reported structure of daunomycin bound to d(CGTACG). Although the two daunomycin complexes are similar, there is an interesting sequence dependence of the binding of the amino sugar to the A-T base pair outside the intercalation site. The complex of daunomycin with d(CGATCG) has tighter binding than the complex with d(CGTACG), leading us to infer a sequence preference in the binding of this anthracycline drug. The structures of daunomycin and adriamycin with d(CGATCG) are very similar. However, there are additional solvent interactions with the adriamycin C14 hydroxyl linking it to the DNA. Surprisingly, under the influence of the altered solvation, there is considerable difference in the conformation of spermine in these two complexes. The observed changes in the overall structures of the ternary complexes amplify the small chemical differences between these two antibiotics and provide a possible explanation for the significantly different clinical activities of these important drugs.

About this StructureAbout this Structure

Full crystallographic information is available from OCA.

ReferenceReference

Structural comparison of anticancer drug-DNA complexes: adriamycin and daunomycin., Frederick CA, Williams LD, Ughetto G, van der Marel GA, van Boom JH, Rich A, Wang AH, Biochemistry. 1990 Mar 13;29(10):2538-49. PMID:2334681 Page seeded by OCA on Fri May 2 13:19:37 2008

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OCA

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 [[Image:1d10.gif|left|200px]]
- {{Structure
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-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=1d10 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=1d10 OCA], [http://www.ebi.ac.uk/pdbsum/1d10 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=1d10 RCSB]</span>
-}}
 '''STRUCTURAL COMPARISON OF ANTICANCER DRUG-DNA COMPLEXES. ADRIAMYCIN AND DAUNOMYCIN'''
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 ==About this Structure==
-D10 is a [[Protein complex]] structure of sequences from [http://en.wikipedia.org/wiki/ ]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D10 OCA].
+Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1D10 OCA].
 ==Reference==
 Structural comparison of anticancer drug-DNA complexes: adriamycin and daunomycin., Frederick CA, Williams LD, Ughetto G, van der Marel GA, van Boom JH, Rich A, Wang AH, Biochemistry. 1990 Mar 13;29(10):2538-49. PMID:[http://www.ncbi.nlm.nih.gov/pubmed/2334681 2334681]
-[[Category: Protein complex]]
 [[Category: Boom, J H.Van.]]
 [[Category: Frederick, C A.]]
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 [[Category: Wang, A H.J.]]
 [[Category: Williams, L D.]]
-[[Category: complexed with drug]]
+[[Category: Complexed with drug]]
-[[Category: double helix]]
+[[Category: Double helix]]
-[[Category: right handed dna]]
+[[Category: Right handed dna]]
+''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Fri May  2 13:19:37 2008''
-''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Mar 30 19:32:21 2008''