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

Proc Natl Acad Sci U S A. 2000 Aug 29;97(18):9892-5. doi: 10.1073/pnas.97.18.9892.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Catalytic / chemistry*
  • Antibodies, Catalytic / metabolism
  • Binding Sites
  • Crystallography, X-Ray
  • Haptens / chemistry
  • Immunoglobulin Fab Fragments / chemistry*
  • Immunoglobulin Fab Fragments / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation

Substances

  • Antibodies, Catalytic
  • Haptens
  • Immunoglobulin Fab Fragments

Associated data

  • PDB/1F3D