PDBsum entry 1vso

Membrane protein

PDB id: 1vso

Contents

Protein chain

243 a.a. *

Ligands

AT1

GOL

Waters ×204

* Residue conservation analysis

PDB id:

1vso

Name:

Membrane protein

Title:

Crystal structure of the ligand-binding core of iglur5 in complex with the antagonist (s)-atpo at 1.85 a resolution

Structure:

Glutamate receptor, ionotropic kainate 1. Chain: a. Synonym: glutamate receptor 5, glur-5, glur5. Engineered: yes

Source:

Rattus norvegicus. Norway rat. Organism_taxid: 10116. Gene: grik1, glur5. Expressed in: escherichia coli. Expression_system_taxid: 562.

Resolution:

1.85Å R-factor: 0.202 R-free: 0.231

Authors:

H.Hald,P.Naur,M.Gajhede,J.S.Kastrup

Key ref:

H.Hald et al. (2007). Partial Agonism and Antagonism of the Ionotropic Glutamate Receptor iGLuR5: STRUCTURES OF THE LIGAND-BINDING CORE IN COMPLEX WITH DOMOIC ACID AND 2-AMINO-3-[5-tert-BUTYL-3-(PHOSPHONOMETHOXY)-4-ISOXAZOLYL]PROPIONIC ACID. J Biol Chem, 282, 25726-25736. PubMed id: 17581823 DOI: 10.1074/jbc.M700137200

Date:

29-Mar-07 Release date: 03-Jul-07

Protein chain

P22756  (GRIK1_RAT) -  Glutamate receptor ionotropic, kainate 1 from Rattus norvegicus

Seq: 949 a.a.

Struc: 243 a.a.*

* PDB and UniProt seqs differ at 1 residue position (black cross)

Enzyme reactions

• Enzyme class: E.C.?

DOI no: 10.1074/jbc.M700137200

J Biol Chem 282:25726-25736 (2007)

PubMed id: 17581823

Partial Agonism and Antagonism of the Ionotropic Glutamate Receptor iGLuR5: STRUCTURES OF THE LIGAND-BINDING CORE IN COMPLEX WITH DOMOIC ACID AND 2-AMINO-3-[5-tert-BUTYL-3-(PHOSPHONOMETHOXY)-4-ISOXAZOLYL]PROPIONIC ACID.

H.Hald, P.Naur, D.S.Pickering, D.Sprogøe, U.Madsen, D.B.Timmermann, P.K.Ahring, T.Liljefors, A.Schousboe, J.Egebjerg, M.Gajhede, J.S.Kastrup.

ABSTRACT

More than 50 structures have been reported on the ligand-binding core of the ionotropic glutamate receptor iGluR2 that belongs to the 2-amino-3-(3-hydroxy-5-methyl-4-isoxazolyl)propionic acid-type of receptors. In contrast, the ligand-binding core of the kainic acid-type receptor iGluR5 has only been crystallized with three different ligands. Hence, additional structures of iGluR5 are needed to broaden the understanding of the ligand-binding properties of iGluR5, and the conformational changes leading to channel opening and closing. Here, we present two structures of the ligand-binding core of iGluR5; one as a complex with the partial agonist (2S,3S,4S)-3-carboxymethyl-4-[(1Z,3E,5R)-5-carboxy-1-methyl-hexa-1,3-dienyl]-pyrrolidine-2-carboxylic acid (domoic acid) and one as a complex with the antagonist (S)-2-amino-3-[5-tert-butyl-3-(phosphonomethoxy)-4-isoxazolyl]propionic acid ((S)-ATPO). In agreement with the partial agonist activity of domoic acid, the ligand-binding core of the iGluR5 complex is stabilized by domoic acid in a conformation that is 11 degrees more open than the conformation observed in the full agonist (S)-glutamic acid complex. This is primarily caused by the 5-carboxy-1-methyl-hexa-1,3-dienyl moiety of domoic acid and residues Val(685)-Thr(690) of iGluR5. An even larger domain opening of 28 degrees is introduced upon binding of the antagonist (S)-ATPO. It appears that the span of domain opening is much larger in the ligand-binding core of iGluR5 (30 degrees ) compared with what has been observed in iGluR2 (19 degrees ). Similarly, much larger variation in the distances between transmembrane linker residues in the two protomers comprising the dimer is observed in iGluR5 as compared with iGluR2.

Selected figure(s)

Figure 1.
FIGURE 1. Chemical structures of domoic acid, kainic acid, (S)-ATPO, UBP302, and UBP310. The atom numbering of domoic acid is shown in italics and is according to Nanao et al. (46) (PDB entry code 1YAE). The numbering of (S)-ATPO is according to Hogner et al. (14) (PDB entry code 1N0T). See abbreviations for compound names.

Figure 4.
FIGURE 4. Two-dimensional ligand-receptor interaction plots of iGluR5-S1S2 in complex with domoic acid (A) and (S)-ATPO (B). iGluR5-S1S2 polar residues are shown as purple circles, acidic residues as purple/red, basic residues as purple/blue, and hydrophobic residues in green. Contacts from ligand to receptor side chains as calculated by the program MOE are shown as green arrows and from ligand to receptor backbone as blue arrows. Water molecules in contact with ligands are shown as white circles and their contacts as yellow lines. The extent of ligand and receptor exposure is shown as blue spheres differing in size.

The above figures are reprinted by permission from the ASBMB: J Biol Chem (2007, 282, 25726-25736) copyright 2007.

Figures were selected by an automated process.