Solution structure of DAPI selectively bound in the minor groove of a DNA T.T mismatch-containing site: NMR and molecular dynamics studies

The solution structure of the complex between 4', 6-diamidino-2-phenylindole (DAPI) and DNA oligomer [d(GCGATTCGC)]2, containing a central T.T mismatch, has been characterized by combined use of proton one- and two-dimensional NMR spectroscopy, molecular mechanics and molecular dynamics computa...

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Bibliographic Details
Published in:Nucleic acids research 1998-10, Vol.26 (20), p.4706-4713
Main Authors: Trotta, E, Paci, M
Format: Article
Language:English
Subjects:
Base Pair Mismatch
Base Pairing
Binding Sites
Computer Simulation
Indoles - chemistry
Indoles - metabolism
Magnetic Resonance Spectroscopy
Models, Molecular
Nucleic Acid Conformation
Oligodeoxyribonucleotides - chemistry
Oligodeoxyribonucleotides - genetics
Oligodeoxyribonucleotides - metabolism
Protons
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Summary:The solution structure of the complex between 4', 6-diamidino-2-phenylindole (DAPI) and DNA oligomer [d(GCGATTCGC)]2, containing a central T.T mismatch, has been characterized by combined use of proton one- and two-dimensional NMR spectroscopy, molecular mechanics and molecular dynamics computations including relaxation matrix refinement. The results show that the DAPI molecule binds in the minor groove of the central region 5'-ATT-3' of the DNA oligomer, which predominantly adopts a duplex structure with a global right-handed B-like conformation. In the final models of the complex, the DAPI molecule is located nearly isohelical with its NH indole proton oriented towards the DNA helix axis and forming a bifurcated hydrogen bond with the carbonyl O2 groups of a mismatched T5 and the T6 residue of the opposite strand. Mismatched thymines adopt a wobble base pair conformation and are found stacked between the flanking base pairs, inducing only minor local conformational changes in global duplex structure. In addition, no other binding mechanisms were observed, showing that minor groove binding of DAPI to the mismatch-containing site is favoured in comparison with any other previously reported interaction with G.C sequences.
ISSN:0305-1048
1362-4962