Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

The AT-selective drug berenil has been co-crystallized with the dodecanucleotide sequence d(CGCAAATTTGCG)2. The crystal structure has been solved to a resolution of 2.0 A and an R factor of 18.3%, with the location of 65 water molecules. The drug is symmetrically bound in the 5'-AATT region of the minor groove, with its amidinium groups hydrogen-bonding to O-2 atoms of the thymine base at each end of the binding site. This arrangement is distinct from that previously found for berenil with the sequence d(CGCGAATTCGCG)2, which has the drug bound to the sequencing 5'-ATT via hydrogen bonds to adenine N-3 atoms with the involvement of a bridging water molecule at one end of the binding site. The reasons for these differences are discussed in terms of changes in helical parameters; in particular propeller twist and base-pair roll are considered to be important. The conformational and base-pair geometry of the dodecanucleotide in the structure reported here, is closely similar to that for the native structure, suggesting that the 5'-AAATTT sequence does not significantly alter during drug binding, either because of its inflexibility or because its geometry is nearly ideal for berenil binding.

Original publication

DOI

10.1016/0022-2836(92)90962-j

Type

Journal article

Journal

J Mol Biol

Publication Date

20/07/1992

Volume

226

Pages

481 - 490

Keywords

Base Sequence, Binding Sites, Computer Graphics, Crystallography, DNA, Diminazene, Hydrogen Bonding, Models, Molecular, Molecular Sequence Data, Molecular Structure, Nucleic Acid Conformation, Oligodeoxyribonucleotides, Structure-Activity Relationship, Water