 |
PDBsum entry 1d10
|
|
|
|
References listed in PDB file
|
 |
|
Key reference
|
|
|
Title
|
|
Structural comparison of anticancer drug-Dna complexes: adriamycin and daunomycin.
|
|
|
Authors
|
|
C.A.Frederick,
L.D.Williams,
G.Ughetto,
G.A.Van der marel,
J.H.Van boom,
A.Rich,
A.H.Wang.
|
|
|
Ref.
|
|
Biochemistry, 1990,
29,
2538-2549.
[DOI no: ]
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
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.
|
|
|
|
|
|
|
|
Headers
|
|
|
|
|
|
