Structural evidence for a programmed general base in the active site of a catalytic antibody

Béatrice Golinelli-Pimpaneau (1) , Olivier Gonçalves (2) , Thierry Dintinger , Dominique Blanchard (3) , Marcel Knossow (4) , Charles Tellier (5)

1 LEBS - Laboratoire d'Enzymologie et Biochimie Structurales
2 GEPEA-BAM - Bioprocédés Appliqués aux Microalgues
3 LMRS - Laboratoire de Mathématiques Raphaël Salem
4 MIKICA - Biochimie Structurale des Microtubules, des Kinésines et de leurs Cargos
5 U3B - Unité de Biotechnologie, Biocatalyse et Biorégulation

The crystal structure of the complex of a catalytic antibody with its cationic hapten at 1.9-Å resolution demonstrates that the hapten amidinium group is stabilized through an ionic pair interaction with the carboxylate of a combining-site residue. The location of this carboxylate allows it to act as a general base in an allylic rearrangement. When compared with structures of other antibody complexes in which the positive moiety of the hapten is stabilized mostly by cation-interactions, this structure shows that the amidinium moiety is a useful candidate to elicit a carboxylate in an antibody combining site at a predetermined location with respect to the hapten. More generally, this structure highlights the advantage of a bidentate hapten for the programmed positioning of a chemically reactive residue in an antibody through charge comple-mentarity to the hapten

Domaines: Chimie

Béatrice Golinelli-Pimpaneau, Olivier Gonçalves, Thierry Dintinger, Dominique Blanchard, Marcel Knossow, et al.. Structural evidence for a programmed general base in the active site of a catalytic antibody. Proceedings of the National Academy of Sciences of the United States of America, 2000, ⟨10.1073/pnas.97.18.9892⟩. ⟨hal-01916755v2⟩