ON THE POTENTIAL ROLE OF THE AMINO NITROGEN ATOM AS A HYDROGEN-BOND ACCEPTOR IN MACROMOLECULES

Crystallographic studies of duplex DNA have indicated that opposing ex ocyclic amino groups may form close NH...N contacts. To study the natu re of such interactions, we have examined the database of small molecu le, high-resolution crystal structures for more accurate examples of t his type of unconventional interaction. We have found cases where the amino groups in guanine and adenine bases accept hydrogen bonds from c onventional donors, such as arn;ino or hydroxyl groups. More frequentl y, the purine amino group was found to contact closely electro-positiv e C-H groups. Searches of the nucleic acid structural databases also y ielded several examples where the purine amino group is contacted by h ydrogen bond donors in macromolecules. Ab initio calculations indicate that the hydrogen-amino contact is improved energetically when the am ino group moves from the conventional geometry, where all atoms are co -planar with the base, to one in which the hydrogen atoms lie out of t he plane and the nitrogen is at the apex of a pyramid, resulting in po larization of the amino group. The combined structural and theoretical data suggest that the amino group is flexible, and can accommodate cl ose contacts, because the resulting polarization permits electropositi ve atoms to approach the amino group nitrogen more closely than expect ed for their conventional van der Waals radii. The flexibility of the amino group may permit particular DNA conformations that enforce hydro gen-amino contacts to optimize favorable stacking interactions, and it may play a role in the recognition of nucleosides. We speculate that the amino group can accept hydrogen bonds under special circumstances in macromolecules, and that this ability might play a mechanistic role in catalytic processes such as deamination or amino transfer. (C) 199 8 Academic Press.