REFINED SOLUTION STRUCTURE OF A DNA HETERODUPLEX CONTAINING AN ALDEHYDIC ABASIC SITE

The solution structure of the DNA duplex d(C(1)G(2)C(3)G(4) 21)G(20)C( 19)T(18)A(17)T(16)G(15)C(14)G(13)G(12)), with D indicating a deoxyribo se aldehyde abasic site and numbering from 5' to 3', has been determin ed by the combined use of NMR and restrained molecular dynamics. The P -31 and P-31-H-1 correlation data indicate that the backbones of these duplex DNAs are regular. One- and two-dimensional H-1 NMR data indica te that the duplexes are right-handed and B-form. Conformational chang es due to the presence of the abasic site extends to the base pairs ad jacent to the lesion site with the local conformation of the DNA being dependent on whether the abasic site is in the alpha or beta configur ation. When the sugar of the abasic site is in the beta configuration the deoxyribose is within the helix, whereas when the sugar is in the cu configuration the deoxyribose is out of the helix. The base of resi due A(17) in the position opposite the abasic site is predominantly st acked in the helix in both cases. A water molecule can apparently form a hydrogen bond bridge between the beta abasic site and A(17).