Three-dimensional structure of the ligand-binding core of GluR2 in complex with the agonist (S)-ATPA: implications for receptor subunit selectivity.
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.
Lunn
Marie-Louise
ML
Department of Medicinal Chemistry, Pharmaceutical University of Denmark, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
Hogner
Anders
A
Stensbøl
Tine B
TB
Gouaux
Eric
E
Egebjerg
Jan
J
Kastrup
Jette S
JS
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
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