Stabilization of bound polycyclic aromatic hydrocarbons by a pi-cation interaction

Proteins can use aromatic side-chains to stabilize bound cationic ligands t hrough cation-pi interactions. Here, we report the first example of the rec iprocal process, termed pi-cation, in which a cationic protein side-chain s tabilizes a neutral aromatic ligand. Site-directed mutagenesis revealed tha t an arginine side-chain located in the deep binding pocket of a monoclonal antibody (4D5) is essential for binding the neutral polynuclear aromatic h ydrocarbon benzo[a]pyrene. This Arg was very likely selected for in the pri mary response, further underscoring the importance of the pi-cation interac tion for ligand binding, which should be considered in protein analysis and design when Ligands include aromatic groups. (C) 2000 Academic Press.