Structural evidence for a programmed general base in the active site of a catalytic antibody.
The crystal structure of the complex of a catalytic antibody with its cationic hapten at 1.9-A 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-pi 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 complementarity to the hapten.
Golinelli-Pimpaneau
B
B
Laboratoire d'Enzymologie et Biochimie Structurales, Centre National de la Recherche Scientifique, Bâtiment 34, 1 Avenue de la Terrasse, 91198 Gif-sur-Yvette Cedex, France. beatrice.golinelli@lebs.cnrs-gif.fr
Goncalves
O
O
Dintinger
T
T
Blanchard
D
D
Knossow
M
M
Tellier
C
C
D000595:Amino Acid Sequence; D017151:Antibodies, Catalytic / Q000737:chemistry* / Q000378:metabolism; D001665:Binding Sites; D018360:Crystallography, X-Ray; D006241:Haptens / Q000737:chemistry; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry* / Q000378:metabolism; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation
D017151:Antibodies, Catalytic; D006241:Haptens; D007140:Immunoglobulin Fab Fragments