Surprising roles of electrostatic interactions in DNA-ligand complexes

The positions of cations in x‐ray structures are modulated by sequence, conformation, and ligand interactions. The goal here is to use x‐ray diffraction to help resolve structural and thermodynamic roles of specifically localized cations in DNA–anthracycline complexes. We describe a 1.34 A˚ resoluti...

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Bibliographic Details
Published in:Biopolymers 2003-05, Vol.69 (1), p.87-99
Main Authors: Howerton, Shelley B., Nagpal, Akankasha, Dean Williams, Loren
Format: Article
Language:English
Subjects:
adriamycin
alkaline metal
anomalous scattering
Antibiotics, Antineoplastic - chemistry
Base Sequence
Binding Sites
Crystallography, X-Ray
Databases, Nucleic Acid
daunomycin
DNA - chemistry
Doxorubicin - chemistry
intercalation
Kinetics
Ligands
major groove
minor groove
Models, Molecular
Molecular Conformation
Nucleic Acid Conformation
Oligodeoxyribonucleotides - chemistry
Static Electricity
thallium
x-ray diffraction
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Summary:The positions of cations in x‐ray structures are modulated by sequence, conformation, and ligand interactions. The goal here is to use x‐ray diffraction to help resolve structural and thermodynamic roles of specifically localized cations in DNA–anthracycline complexes. We describe a 1.34 A˚ resolution structure of a CGATCG2–adriamycin2 complex obtained from crystals grown in the presence of thallium (I) ions. Tl+ can substitute for biological monovalent cations, but is readily detected by distinctive x‐ray scattering, obviating analysis of subtle differences in coordination geometry and x‐ray scattering of water, sodium, potassium, and ammonium. Six localized Tl+ sites are observable adjacent to each CGATCG2–adriamycin2 complex. Each of these localized monovalent cations are found within the G‐tract major groove of the intercalated DNA–drug complex. Adriamycin appears to be designed by nature to interact favorably with the electrostatic landscape of DNA, and to conserve the distribution of localized cationic charge. Localized inorganic cations in the major groove are conserved upon binding of adriamycin. In the minor groove, inorganic cations are substituted by a cationic functional group of adriamycin. This partitioning of cationic charge by adriamycin into the major groove of CG base pairs and the minor groove of AT base pairs may be a general feature of sequence‐specific DNA–small molecule interactions and a potentially useful important factor in ligand design. © 2003 Wiley Periodicals, Inc. Biopolymers 69: 87–99, 2003
ISSN:0006-3525
1097-0282
DOI:10.1002/bip.10319