Catalysis of decarboxylation by a preorganized heterogeneous microenvironment: crystal structures of abzyme 21D8

J Mol Biol. 2000 Oct 6;302(5):1213-25. doi: 10.1006/jmbi.2000.4503.

Abstract

Antibody 21D8 catalyzes the solvent-sensitive decarboxylation of 3-carboxybenzisoxazoles. The crystal structure of chimeric Fab 21D8 with and without hapten at 1.61 A and 2.10 A, respectively, together with computational analysis, shows how a melange of polar and non-polar sites are exploited to achieve both substrate binding and acceleration of a reaction normally facilitated by purely aprotic dipolar media. The striking similarity of the decarboxylase and a series of unrelated esterase antibodies also highlights the chemical versatility of structurally conserved anion binding sites and the relatively subtle changes involved in fine-tuning the immunoglobulin pocket for recognition of different ligands and catalysis of different reactions.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Anions / metabolism
  • Antibodies, Catalytic / chemistry*
  • Antibodies, Catalytic / genetics
  • Antibodies, Catalytic / immunology
  • Antibodies, Catalytic / metabolism*
  • Binding Sites
  • Binding Sites, Antibody
  • Carboxy-Lyases / chemistry*
  • Carboxy-Lyases / genetics
  • Carboxy-Lyases / immunology
  • Carboxy-Lyases / metabolism*
  • Catalysis
  • Cloning, Molecular
  • Crystallography, X-Ray
  • Esterases / chemistry
  • Esterases / immunology
  • Esterases / metabolism
  • Haptens / chemistry
  • Haptens / immunology
  • Humans
  • Hydrogen Bonding
  • Immunoglobulin Fab Fragments / chemistry
  • Immunoglobulin Fab Fragments / genetics
  • Immunoglobulin Fab Fragments / immunology
  • Immunoglobulin Fab Fragments / metabolism
  • Isoxazoles / chemistry
  • Isoxazoles / metabolism
  • Ligands
  • Mice
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation
  • Recombinant Fusion Proteins / chemistry
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / immunology
  • Recombinant Fusion Proteins / metabolism
  • Serum Albumin / chemistry
  • Serum Albumin / metabolism
  • Solvents
  • Static Electricity

Substances

  • Anions
  • Antibodies, Catalytic
  • Haptens
  • Immunoglobulin Fab Fragments
  • Isoxazoles
  • Ligands
  • Recombinant Fusion Proteins
  • Serum Albumin
  • Solvents
  • abzyme 21D8
  • Esterases
  • Carboxy-Lyases

Associated data

  • PDB/1C5B
  • PDB/1C5C