GluR2 ligand-binding core complexes: Importance of the isoxazolol moiety and 5-substituent for the binding mode of AMPA-type agonists

C. Kasper, M. L. Lunn, T. Liljefors, Eric Gouaux, J. Egebjerg, J. S. Kastrup

Research output: Contribution to journalArticle

39 Citations (Scopus)

Abstract

X-ray structures of the GluR2 ligand-binding core in complex with (S)-Des-Me-AMPA and in the presence and absence of zinc ions have been determined. (S)-Des-Me-AMPA, which is devoid of a substituent in the 5-position of the isoxazolol ring, only has limited interactions with the partly hydrophobic pocket of the ligand-binding site, and adopts an AMPA-like binding mode. The structures, in comparison with other agonist complex structures, disclose the relative importance of the isoxazolol ring and of the substituent in the 5-position for the mode of binding. A relationship appears to exist between the extent of interaction of the ligand with the hydrophobic pocket and the affinity of the ligand.

Original languageEnglish (US)
Pages (from-to)173-178
Number of pages6
JournalFEBS Letters
Volume531
Issue number2
DOIs
StatePublished - Nov 6 2002
Externally publishedYes

Fingerprint

alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
Ligands
Zinc
Binding Sites
X-Rays
Ions
X rays
2-amino-3-(3-hydroxy-4-isoxazoyl)propionic acid

Keywords

  • Agonist
  • AMPA analogue
  • Ionotropic glutamate receptor
  • Ligand-binding core
  • X-ray crystallography

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

GluR2 ligand-binding core complexes : Importance of the isoxazolol moiety and 5-substituent for the binding mode of AMPA-type agonists. / Kasper, C.; Lunn, M. L.; Liljefors, T.; Gouaux, Eric; Egebjerg, J.; Kastrup, J. S.

In: FEBS Letters, Vol. 531, No. 2, 06.11.2002, p. 173-178.

Research output: Contribution to journalArticle

Kasper, C. ; Lunn, M. L. ; Liljefors, T. ; Gouaux, Eric ; Egebjerg, J. ; Kastrup, J. S. / GluR2 ligand-binding core complexes : Importance of the isoxazolol moiety and 5-substituent for the binding mode of AMPA-type agonists. In: FEBS Letters. 2002 ; Vol. 531, No. 2. pp. 173-178.
@article{2a053a225265433fbc00033fbc049b8c,
title = "GluR2 ligand-binding core complexes: Importance of the isoxazolol moiety and 5-substituent for the binding mode of AMPA-type agonists",
abstract = "X-ray structures of the GluR2 ligand-binding core in complex with (S)-Des-Me-AMPA and in the presence and absence of zinc ions have been determined. (S)-Des-Me-AMPA, which is devoid of a substituent in the 5-position of the isoxazolol ring, only has limited interactions with the partly hydrophobic pocket of the ligand-binding site, and adopts an AMPA-like binding mode. The structures, in comparison with other agonist complex structures, disclose the relative importance of the isoxazolol ring and of the substituent in the 5-position for the mode of binding. A relationship appears to exist between the extent of interaction of the ligand with the hydrophobic pocket and the affinity of the ligand.",
keywords = "Agonist, AMPA analogue, Ionotropic glutamate receptor, Ligand-binding core, X-ray crystallography",
author = "C. Kasper and Lunn, {M. L.} and T. Liljefors and Eric Gouaux and J. Egebjerg and Kastrup, {J. S.}",
year = "2002",
month = "11",
day = "6",
doi = "10.1016/S0014-5793(02)03496-8",
language = "English (US)",
volume = "531",
pages = "173--178",
journal = "FEBS Letters",
issn = "0014-5793",
publisher = "Elsevier",
number = "2",

}

TY - JOUR

T1 - GluR2 ligand-binding core complexes

T2 - Importance of the isoxazolol moiety and 5-substituent for the binding mode of AMPA-type agonists

AU - Kasper, C.

AU - Lunn, M. L.

AU - Liljefors, T.

AU - Gouaux, Eric

AU - Egebjerg, J.

AU - Kastrup, J. S.

PY - 2002/11/6

Y1 - 2002/11/6

N2 - X-ray structures of the GluR2 ligand-binding core in complex with (S)-Des-Me-AMPA and in the presence and absence of zinc ions have been determined. (S)-Des-Me-AMPA, which is devoid of a substituent in the 5-position of the isoxazolol ring, only has limited interactions with the partly hydrophobic pocket of the ligand-binding site, and adopts an AMPA-like binding mode. The structures, in comparison with other agonist complex structures, disclose the relative importance of the isoxazolol ring and of the substituent in the 5-position for the mode of binding. A relationship appears to exist between the extent of interaction of the ligand with the hydrophobic pocket and the affinity of the ligand.

AB - X-ray structures of the GluR2 ligand-binding core in complex with (S)-Des-Me-AMPA and in the presence and absence of zinc ions have been determined. (S)-Des-Me-AMPA, which is devoid of a substituent in the 5-position of the isoxazolol ring, only has limited interactions with the partly hydrophobic pocket of the ligand-binding site, and adopts an AMPA-like binding mode. The structures, in comparison with other agonist complex structures, disclose the relative importance of the isoxazolol ring and of the substituent in the 5-position for the mode of binding. A relationship appears to exist between the extent of interaction of the ligand with the hydrophobic pocket and the affinity of the ligand.

KW - Agonist

KW - AMPA analogue

KW - Ionotropic glutamate receptor

KW - Ligand-binding core

KW - X-ray crystallography

UR - http://www.scopus.com/inward/record.url?scp=0037032411&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037032411&partnerID=8YFLogxK

U2 - 10.1016/S0014-5793(02)03496-8

DO - 10.1016/S0014-5793(02)03496-8

M3 - Article

C2 - 12417307

AN - SCOPUS:0037032411

VL - 531

SP - 173

EP - 178

JO - FEBS Letters

JF - FEBS Letters

SN - 0014-5793

IS - 2

ER -