CH/Π interaction in the packing of the adenine ring in protein structures

Abstract

One of the weak but directional interactions in protein structures involves the O-H or N-H bond that is oriented along the center of a benzene ring. Even a CH group can have enthalpically favorable interaction with an aromatic ring if the latter is made electron-rich by incorporating nitrogen atoms. This CH/Π interaction is brought into play in the binding of the adenine rings, which are sandwiched between protein residues such that saturated carbon atoms are on top of ring nitrogen atoms at distances of approximately 3.7 Å. There is a preponderance of residues with branched side-chains that have specific locations on the tertiary fold that is employed for binding the adenine-containing cofactors. In addition to the conventional hydrogen bonding, the CH/Π interaction can be important for the recognition of DNA and RNA molecules by proteins. The main- and the side-chain atoms of the same residue can participate in both types of interaction, so that a protein can engage an adenine moiety by employing only a limited number of residues.