Immunological origins of binding and catalysis in a Diels-Alderase antibody

Science. 1998 Mar 20;279(5358):1929-33. doi: 10.1126/science.279.5358.1929.

Abstract

The three-dimensional structure of an antibody (39-A11) that catalyzes a Diels-Alder reaction has been determined. The structure suggests that the antibody catalyzes this pericyclic reaction through a combination of packing and hydrogen-bonding interactions that control the relative geometries of the bound substrates and electronic distribution in the dienophile. A single somatic mutation, serine-91 of the light chain to valine, is largely responsible for the increase in affinity and catalytic activity of the affinity-matured antibody. Structural and functional studies of the germ-line precursor suggest that 39-A11 and related antibodies derive from a family of germ-line genes that have been selected throughout evolution for the ability of the encoded proteins to form a polyspecific combining site. Germ line-encoded antibodies of this type, which can rapidly evolve into high-affinity receptors for a broad range of structures, may help to expand the binding potential associated with the structural diversity of the primary antibody repertoire.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antibodies / chemistry
  • Antibodies / genetics
  • Antibodies / immunology
  • Antibodies / metabolism
  • Antibodies, Catalytic / chemistry*
  • Antibodies, Catalytic / genetics
  • Antibodies, Catalytic / immunology
  • Antibodies, Catalytic / metabolism*
  • Antibody Affinity
  • Antibody Specificity
  • Binding Sites
  • Binding Sites, Antibody
  • Catalysis
  • Chemistry, Organic
  • Cloning, Molecular
  • Crystallography, X-Ray
  • Evolution, Molecular
  • Germ-Line Mutation
  • Haptens / immunology
  • Hydrogen Bonding
  • Immunoglobulin Fab Fragments / immunology
  • Immunoglobulin Fab Fragments / metabolism
  • Models, Molecular
  • Molecular Sequence Data
  • Mutation
  • Organic Chemistry Phenomena
  • Protein Conformation
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism

Substances

  • Antibodies
  • Antibodies, Catalytic
  • Haptens
  • Immunoglobulin Fab Fragments
  • Recombinant Proteins

Associated data

  • PDB/1A4J
  • PDB/1A4K