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; E Gouaux; J Egebjerg; Jette Sandholm Jensen Kastrup

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, E Gouaux, J Egebjerg, Jette Sandholm Jensen Kastrup

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 language	English
Journal	F E B S Letters
Volume	531
Issue number	2
Pages (from-to)	173-8
Number of pages	6
ISSN	0014-5793
Publication status	Published - 6 Nov 2002

Keywords

Animals
Binding Sites
Crystallography, X-Ray
Hydrogen Bonding
Hydrophobic and Hydrophilic Interactions
Isoxazoles
Ligands
Macromolecular Substances
Methionine
Models, Molecular
Peptides
Protein Binding
Receptors, AMPA
Sulfates
Zinc
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid

Cite this

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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 = "Animals, Binding Sites, Crystallography, X-Ray, Hydrogen Bonding, Hydrophobic and Hydrophilic Interactions, Isoxazoles, Ligands, Macromolecular Substances, Methionine, Models, Molecular, Peptides, Protein Binding, Receptors, AMPA, Sulfates, Zinc, alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid",

author = "C Kasper and M-L Lunn and T Liljefors and E Gouaux and J Egebjerg and Kastrup, {Jette Sandholm Jensen}",

year = "2002",

month = nov,

day = "6",

language = "English",

volume = "531",

pages = "173--8",

journal = "F E B S Letters",

issn = "0014-5793",

publisher = "JohnWiley & Sons Ltd",

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, 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

SN - 0014-5793

VL - 531

SP - 173

EP - 178

JO - F E B S Letters

JF - F E B S Letters

IS - 2

ER -

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

Abstract

Keywords

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