title: Three-dimensional structure of the ligand-binding core of GluR2 in complex with the agonist (S)-ATPA: implications for receptor subunit selectivity.
abstract: 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.
authors.affiliation: Department of Medicinal Chemistry, Pharmaceutical University of Denmark, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Marie-Louise
authors.initials: ML
authors.lastname: Lunn
authors.forename: Anders
authors.initials: A
authors.lastname: Hogner
authors.forename: Tine B
authors.initials: TB
authors.lastname: Stensbøl
authors.forename: Eric
authors.initials: E
authors.lastname: Gouaux
authors.forename: Jan
authors.initials: J
authors.lastname: Egebjerg
authors.forename: Jette S
authors.initials: JS
authors.lastname: Kastrup
mesh_terms: D001665:Binding Sites; D018360:Crystallography, X-Ray; D019281:Dimerization; D018690:Excitatory Amino Acid Agonists / Q000737:chemistry*; D007555:Isoxazoles / Q000737:chemistry*; D008024:Ligands; D008958:Models, Molecular; D011422:Propionates / Q000737:chemistry*; D011487:Protein Conformation; D021122:Protein Subunits; D018091:Receptors, AMPA / Q000819:agonists / Q000737:chemistry*; D013237:Stereoisomerism; D015032:Zinc / Q000737:chemistry
chemical_list: D018690:Excitatory Amino Acid Agonists; D007555:Isoxazoles; D008024:Ligands; D011422:Propionates; D021122:Protein Subunits; D018091:Receptors, AMPA; C081662:alpha-amino-3-hydroxy-5-tert-butyl-4-isoxazolepropionate; D015032:Zinc; C104722:glutamate receptor ionotropic, AMPA 2