Protein-ligand binding amino-aromatic interactions

Like the other weakly polar interactions, amino-aromatic interactions are a mechanism of protein-ligand binding. Perutz et al. (1986) described a series of X-ray crystallographic studies of drugs and peptides bound to deoxy-Hb A. They characterized an amino-aromatic interaction between the 8+ N8—H group of asparagine-108 with the 8 7r-electron cloud of one of the phenyl rings of bezafibrate (see Fig. 20). 

S. K. Burley and G. A. Petsko cover the field of noncovalent interactions of proteins, with particular emphasis on weakly polar interactions. Their presentation of the whole field of electrostatic interactions should be of value to many workers in protein chemistry, but their special concern is with the weaker, but very important, interactions involving aromatic side chains, their orientation relative to one another, to oxygen and sulfur atoms, to amino groups, and to aromatic ligands that may bind to the protein. These interactions, only recently recognized for their influence on protein structure, play an important part in the formation of aromatic clusters in the interior of globular proteins and in other features of structure. The authors provide numerous illustrations of the principles involved, from recently determined structures, of both small molecules and proteins. 

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