PDBsum entry 1mqd

Membrane protein

PDB id: 1mqd

Contents

Protein chains

258 a.a. *

Ligands

SO4 ×3

SHI ×4

GOL

Waters ×2626

* Residue conservation analysis

PDB id:

1mqd

Name:

Membrane protein

Title:

X-ray structure of the glur2 ligand-binding core (s1s2j) in complex with (s)-des-me-ampa at 1.46 a resolution. Crystallization in the presence of lithium sulfate.

Structure:

Glutamate receptor subunit 2. Chain: a, b, c, d. Fragment: glur2-flop ligand-binding core (s1s2j). Synonym: glur-2. Engineered: yes. Other_details: tetherd dimer linked by gly 115 and thr 116

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Expressed in: escherichia coli bl21(de3). Expression_system_taxid: 469008.

Biol. unit:

Dimer (from PDB file)

Resolution:

1.46Å R-factor: 0.180 R-free: 0.192

Authors:

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

Key ref:

C.Kasper et al. (2002). GluR2 ligand-binding core complexes: importance of the isoxazolol moiety and 5-substituent for the binding mode of AMPA-type agonists. FEBS Lett, 531, 173-178. PubMed id: 12417307 DOI: 10.1016/S0014-5793(02)03496-8

Date:

16-Sep-02 Release date: 01-Jul-03

Protein chains

P19491  (GRIA2_RAT) -  Glutamate receptor 2 from Rattus norvegicus

Seq: 883 a.a.

Struc: 258 a.a.*

* PDB and UniProt seqs differ at 2 residue positions (black crosses)

DOI no: 10.1016/S0014-5793(02)03496-8

FEBS Lett 531:173-178 (2002)

PubMed id: 12417307

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, J.S.Kastrup.

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.

Selected figure(s)

Figure 1.
Fig. 1. A: The GluR2-S1S2J construct, comprising the ligand-binding core of the AMPA-receptor subunit GluR2, is composed of segments S1 and S2, joined by a linker (dashed line). The two domains D1 and D2 are shown in yellow and green, respectively. The amino-terminal domain is outlined as a red sphere, and integral membrane parts are blue. B: The chemical structures of (S)-Des-Me-AMPA, (S)-AMPA and (S)-2-Me-Tet-AMPA.

Figure 3.
Fig. 3. The ligand-binding site of GluR2-S1S2J. A: Interactions between GluR2-S1S2J and (S)-Des-Me-AMPA. Dashed lines indicate potential hydrogen bonds/ionic interactions (up to 3.3 Å). Water molecules are displayed as red spheres. Nitrogen atoms are shown in blue, oxygen atoms in red, and sulfur atoms in dark green. B: Superimposition of the (S)-Des-Me-AMPA (cyan), (S)-AMPA (green), (S)-2-Me-Tet-AMPA (magenta) and (S)-glutamate (yellow) complexes (shown in stereo). For all structures MolA is used as a representative. The conformation of Met708 in the glutamate complex is unique for MolA, as the other two molecules have extended Met708 chains.

The above figures are reprinted by permission from the Federation of European Biochemical Societies: FEBS Lett (2002, 531, 173-178) copyright 2002.

Figures were selected by an automated process.