4G8N

Crystal structure of the kainate receptor GluK3 ligand-binding domain in complex with the agonist G8M

Summary for 4G8N

• Entry DOI: 10.2210/pdb4g8n/pdb
• Related: 3S9E
• Descriptor: Glutamate receptor, ionotropic kainate 3, (1S,2R)-2-[(S)-amino(carboxy)methyl]cyclobutanecarboxylic acid, CHLORIDE ION, ... (5 entities in total)
• Functional Keywords: membrane protein, ionotropic glutamate receptor, ligand binding domain, agonist complex, membrane protein-agonist complex, membrane protein/agonist
• Biological source: Rattus norvegicus (rat); More
• Cellular location: Cell membrane; Multi-pass membrane protein: P42264
• Total number of polymer chains: 1
• Total formula weight: 29414.72

Authors

Venskutonyte, R.,Kastrup, J.S.,Frydenvang, K.,Gajhede, M. (deposition date: 2012-07-23, release date: 2012-08-29, Last modification date: 2024-10-30)

Primary citation

Juknaite, L.,Venskutonyte, R.,Assaf, Z.,Faure, S.,Gefflaut, T.,Aitken, D.J.,Nielsen, B.,Gajhede, M.,Kastrup, J.S.,Bunch, L.,Frydenvang, K.,Pickering, D.S.
Pharmacological and structural characterization of conformationally restricted (S)-glutamate analogues at ionotropic glutamate receptors.
J.Struct.Biol., 180:39-46, 2012

PubMed Abstract: Conformationally restricted glutamate analogues have been pharmacologically characterized at AMPA and kainate receptors and the crystal structures have been solved of the ligand (2S,1'R,2'S)-2-(2'-carboxycyclobutyl)glycine (CBG-IV) in complex with the ligand binding domains of the AMPA receptor GluA2 and the kainate receptor GluK3. These structures show that CBG-IV interacts with the binding pocket in the same way as (S)-glutamate. The binding affinities reveal that CBG-IV has high affinity at the AMPA and kainate receptor subtypes. Appreciable binding affinity of CBG-IV was not observed at NMDA receptors, where the introduction of the carbocyclic ring is expected to lead to a steric clash with binding site residues. CBG-IV was demonstrated to be an agonist at both GluA2 and the kainate receptor GluK1. CBG-IV showed high affinity binding to GluK1 compared to GluA2, GluK2 and GluK3, which exhibited lower affinity for CBG-IV. The structure of GluA2 LBD and GluK3 LBD in complex with CBG-IV revealed similar binding site interactions to those of (S)-glutamate. No major conformational rearrangements compared to the (S)-glutamate bound conformation were found in GluK3 in order to accommodate CBG-IV, in contrast with GluA2 where a shift in lobe D2 binding site residues occurs, leading to an increased binding cavity volume compared to the (S)-glutamate bound structure.

PubMed: 22789682
DOI: 10.1016/j.jsb.2012.07.001

Experimental method

X-RAY DIFFRACTION (2.3 Å)