ISSN:
0020-7608
Keywords:
Computational Chemistry and Molecular Modeling
;
Atomic, Molecular and Optical Physics
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
The novel B-DNA dodecamer sequence d(CGCGTTAACGCG) and its complex with the anticancer drug netropsin have been determined using single crystal X-ray diffraction methods. The DNA conformations in both structures are compared to understand drug-induced conformational changes. The dodecamers crystallize in isomorphous orthorhombic space group P212121 with cell constants a = 25.49 Å, b = 40.84 Å, and c = 67.02 Å for the DNA itself, and a = 25.70 Å, b = 40.50 Å, and c = 67.00 Å for the complex. X-ray intensity data were collected on a Siemens area detector, and the structures were refined to R factors of about 19%. The DNA molecule is bent 18° in the native structure and 24° in the netropsin complex. The narrow “cleft” formed by the T2A2 sequence at the center serves as the binding site for the drug and on binding expands the cleft from about 4 to 4.3 Å. The drug is engaged in hydrogenbonding interactions with the adenine N3 and thymine O2 atoms in the floor of the minor groove covering the entire tetranucleotide stretch TTAA/AATT.
Additional Material:
2 Ill.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1002/qua.560400720
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