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

ABSTRACT: 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.

SUBMITTER: Golinelli-Pimpaneau B

PROVIDER: S-EPMC27617 | biostudies-literature | 2000 Aug

REPOSITORIES: biostudies-literature

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

Golinelli-Pimpaneau B B Goncalves O O Dintinger T T Blanchard D D Knossow M M Tellier C C

Proceedings of the National Academy of Sciences of the United States of America 20000801 18

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 ...[more]

PMID: 10963661

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