GluR2 ligand-binding core complexes: importance of the isoxazolol moiety and 5-substituent for the binding mode of AMPA-type agonists
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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, E; Egebjerg, J; Kastrup, Jette Sandholm Jensen.
In: F E B S Letters, Vol. 531, No. 2, 06.11.2002, p. 173-8.Research output: Contribution to journal › Journal article › Research › peer-review
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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, E
AU - Egebjerg, J
AU - Kastrup, Jette Sandholm Jensen
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 - Animals
KW - Binding Sites
KW - Crystallography, X-Ray
KW - Hydrogen Bonding
KW - Hydrophobic and Hydrophilic Interactions
KW - Isoxazoles
KW - Ligands
KW - Macromolecular Substances
KW - Methionine
KW - Models, Molecular
KW - Peptides
KW - Protein Binding
KW - Receptors, AMPA
KW - Sulfates
KW - Zinc
KW - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
M3 - Journal article
C2 - 12417307
VL - 531
SP - 173
EP - 178
JO - F E B S Letters
JF - F E B S Letters
SN - 0014-5793
IS - 2
ER -
ID: 44729582