Evolution of shape complementarity and catalytic efficiency from a primordial antibody template

Science. 1999 Dec 17;286(5448):2345-8. doi: 10.1126/science.286.5448.2345.

Abstract

The crystal structure of an efficient Diels-Alder antibody catalyst at 1.9 angstrom resolution reveals almost perfect shape complementarity with its transition state analog. Comparison with highly related progesterone and Diels-Alderase antibodies that arose from the same primordial germ line template shows the relatively subtle mutational steps that were able to evolve both structural complementarity and catalytic efficiency.

Publication types

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

MeSH terms

  • Antibodies, Catalytic / chemistry*
  • Antibodies, Catalytic / genetics
  • Antibodies, Catalytic / metabolism*
  • Binding Sites, Antibody
  • Catalysis
  • Chemical Phenomena
  • Chemistry, Physical
  • Crystallography, X-Ray
  • Evolution, Molecular*
  • Haptens / chemistry
  • Haptens / metabolism
  • Hydrogen Bonding
  • Immunoglobulin Fab Fragments / chemistry
  • Immunoglobulin Fab Fragments / metabolism
  • Ligands
  • Models, Molecular
  • Mutation
  • Progesterone / immunology
  • Protein Conformation
  • Solubility
  • Temperature
  • Templates, Genetic

Substances

  • Antibodies, Catalytic
  • Haptens
  • Immunoglobulin Fab Fragments
  • Ligands
  • Progesterone

Associated data

  • PDB/1C1E