title: Computational structural analysis of an anti-L-amino acid antibody and inversion of its stereoselectivity.
abstract: The binding site of a monoclonal anti-L-amino acid antibody (anti-L-AA) was modeled using the program SWISS-MODEL. Docking experiments with the enantiomers of phenylalanine revealed that the antibody interacts with L-phenylalanine via hydrogen bonds and hydrophobic contacts, whereas the D-enantiomer is rejected due to steric hindrance. Comparison of the sequences of this antibody and an anti-D-amino acid antibody (anti-D-AA) indicates that both immunoglobulins derived from the same germline progenitor. Substitution of four amino acids residues, three in the framework and one in the complementarity determining regions (CDRs), allowed in silico conversion of the anti-L-AA into an antibody that stereoselectively binds D-phenylalanine.
authors.affiliation: Department of Chemistry and Biochemistry, Northern Illinois University, DeKalb 60115-2862, USA.
authors.forename: Daniel I
authors.initials: DI
authors.lastname: Ranieri
authors.forename: Heike
authors.initials: H
authors.lastname: Hofstetter
authors.forename: Oliver
authors.initials: O
authors.lastname: Hofstetter
mesh_terms: D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000737:chemistry* / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D001665:Binding Sites; D003198:Computer Simulation; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010649:Phenylalanine / Q000737:chemistry* / Q000276:immunology*; D016415:Sequence Alignment; D013237:Stereoisomerism
chemical_list: D000911:Antibodies, Monoclonal; D010649:Phenylalanine