Three-dimensional structure of the ligand-binding core of GluR2 in complex with the agonist (S)-ATPA

Implications for receptor subunit selectivity

Marie Louise Lunn, Anders Hogner, Tine B. Stensbøl, Eric Gouaux, Jan Egebjerg, Jette S. Kastrup

Research output: Contribution to journalArticle

47 Citations (Scopus)

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 Zn2+ ions. (S)-ATPA induces a domain closure of ca. 21° 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 (US)
Pages (from-to)872-875
Number of pages4
JournalJournal of Medicinal Chemistry
Volume46
Issue number5
DOIs
StatePublished - Feb 27 2003
Externally publishedYes

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Ligands
Kainic Acid Receptors
AMPA Receptors
Glutamic Acid
X-Rays
Ions
X rays
S(2) complex
propionic acid

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Three-dimensional structure of the ligand-binding core of GluR2 in complex with the agonist (S)-ATPA : Implications for receptor subunit selectivity. / Lunn, Marie Louise; Hogner, Anders; Stensbøl, Tine B.; Gouaux, Eric; Egebjerg, Jan; Kastrup, Jette S.

In: Journal of Medicinal Chemistry, Vol. 46, No. 5, 27.02.2003, p. 872-875.

Research output: Contribution to journalArticle

Lunn, Marie Louise ; Hogner, Anders ; Stensbøl, Tine B. ; Gouaux, Eric ; Egebjerg, Jan ; Kastrup, Jette S. / Three-dimensional structure of the ligand-binding core of GluR2 in complex with the agonist (S)-ATPA : Implications for receptor subunit selectivity. In: Journal of Medicinal Chemistry. 2003 ; Vol. 46, No. 5. pp. 872-875.
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