Three-dimensional structure of the ligand-binding core of GluR2 in complex with the agonist (S)-ATPA: implications for receptor subunit selectivity

J Med Chem. 2003 Feb 27;46(5):872-5. doi: 10.1021/jm021020+.


Two X-ray structures of the GluR2 ligand-binding core in complex with (S)-2-amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid ((S)-ATPA) have been determined with and without Zn(2+) ions. (S)-ATPA induces a domain closure of ca. 21 degrees compared to the apo form. The tert-butyl moiety of (S)-ATPA is buried in a partially hydrophobic pocket and forces the ligand into the glutamate-like binding mode. The structures provide new insight into the molecular basis of agonist selectivity between AMPA and kainate receptors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Crystallography, X-Ray
  • Dimerization
  • Excitatory Amino Acid Agonists / chemistry*
  • Isoxazoles / chemistry*
  • Ligands
  • Models, Molecular
  • Propionates / chemistry*
  • Protein Conformation
  • Protein Subunits
  • Receptors, AMPA / agonists
  • Receptors, AMPA / chemistry*
  • Stereoisomerism
  • Zinc / chemistry


  • Excitatory Amino Acid Agonists
  • Isoxazoles
  • Ligands
  • Propionates
  • Protein Subunits
  • Receptors, AMPA
  • alpha-amino-3-hydroxy-5-tert-butyl-4-isoxazolepropionate
  • Zinc
  • glutamate receptor ionotropic, AMPA 2

Associated data

  • PDB/1NNK
  • PDB/1NNP