title: Stabilization of bound polycyclic aromatic hydrocarbons by a pi-cation interaction.
abstract: Proteins can use aromatic side-chains to stabilize bound cationic ligands through cation-pi interactions. Here, we report the first example of the reciprocal process, termed pi-cation, in which a cationic protein side-chain stabilizes a neutral aromatic ligand. Site-directed mutagenesis revealed that an arginine side-chain located in the deep binding pocket of a monoclonal antibody (4D5) is essential for binding the neutral polynuclear aromatic hydrocarbon benzo[a]pyrene. This Arg was very likely selected for in the primary response, further underscoring the importance of the pi-cation interaction for ligand binding, which should be considered in protein analysis and design when ligands include aromatic groups.
authors.affiliation: Department of Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Pellequer
authors.forename: B
authors.initials: B
authors.lastname: Zhao
authors.forename: H I
authors.initials: HI
authors.lastname: Kao
authors.forename: C W
authors.initials: CW
authors.lastname: Bell
authors.forename: K
authors.initials: K
authors.lastname: Li
authors.forename: Q X
authors.initials: QX
authors.lastname: Li
authors.forename: A E
authors.initials: AE
authors.lastname: Karu
authors.forename: V A
authors.initials: VA
authors.lastname: Roberts
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution / Q000235:genetics; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D000936:Antigen-Antibody Complex / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D001120:Arginine / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D001564:Benzo(a)pyrene / Q000737:chemistry* / Q000378:metabolism*; D001666:Binding Sites, Antibody / Q000235:genetics / Q000276:immunology; D002412:Cations / Q000737:chemistry* / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D006241:Haptens / Q000737:chemistry / Q000276:immunology / Q000378:metabolism; D007135:Immunoglobulin Variable Region / Q000737:chemistry* / Q000235:genetics / Q000276:immunology; D008024:Ligands; D008239:Lysine / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed / Q000235:genetics; D009154:Mutation / Q000235:genetics; D055672:Static Electricity; D013816:Thermodynamics
chemical_list: D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D002412:Cations; D006241:Haptens; D007135:Immunoglobulin Variable Region; D008024:Ligands; D001564:Benzo(a)pyrene; D001120:Arginine; D008239:Lysine