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

Research output: Contribution to journalJournal articleResearchpeer-review

Marie-Louise Lunn, Anders Hogner, Tine B Stensbøl, Eric Gouaux, Jan Egebjerg, Jette Sandholm Jensen Kastrup

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.
Original languageEnglish
JournalJournal of Medicinal Chemistry
Volume46
Issue number5
Pages (from-to)872-5
Number of pages4
ISSN0022-2623
DOIs
Publication statusPublished - 27 Feb 2003

    Research areas

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

ID: 44729638