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Structure of the B‐DNA dodecamer with the reversed central sequence d (CGCGTTAACGCG) and its netropsin complex
Author(s) -
Balendiran K.,
Sundaralingam M.
Publication year - 1991
Publication title -
international journal of quantum chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.484
H-Index - 105
eISSN - 1097-461X
pISSN - 0020-7608
DOI - 10.1002/qua.560400720
Subject(s) - netropsin , dodecameric protein , crystallography , thymine , dna , chemistry , orthorhombic crystal system , molecule , stereochemistry , crystal structure , minor groove , biochemistry , organic chemistry
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 P 2 1 2 1 2 1 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 T 2 A 2 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 TT AA / AA TT.