4GXS

Ligand binding domain of GluA2 (AMPA/glutamate receptor) bound to (-)-kaitocephalin

Summary for 4GXS

• Entry DOI: 10.2210/pdb4gxs/pdb
• Descriptor: Glutamate receptor 2, (5R)-2-[(1S,2R)-2-amino-2-carboxy-1-hydroxyethyl]-5-{(2S)-2-carboxy-2-[(3,5-dichloro-4-hydroxybenzoyl)amino]ethyl}-L-proline, ZINC ION, ... (4 entities in total)
• Functional Keywords: glutamate receptor, glua2, glur2, ampa receptor, neurotransmitter receptor, (-)-kaitocephalin, membrane protein
• Biological source: Rattus norvegicus (brown rat,rat,rats); More
• Cellular location: Cell membrane; Multi-pass membrane protein: P19491
• Total number of polymer chains: 2
• Total formula weight: 58855.43

Authors

Ahmed, A.H.,Oswald, R.E. (deposition date: 2012-09-04, release date: 2012-10-17, Last modification date: 2023-09-13)

Primary citation

Ahmed, A.H.,Hamada, M.,Shinada, T.,Ohfune, Y.,Weerasinghe, L.,Garner, P.P.,Oswald, R.E.
The structure of (-)-kaitocephalin bound to the ligand binding domain of the (S)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/glutamate receptor, GluA2.
J.Biol.Chem., 287:41007-41013, 2012

PubMed Abstract: Glutamate receptors mediate the majority of excitatory synaptic transmission in the central nervous system, and excessive stimulation of these receptors is involved in a variety of neurological disorders and neuronal damage from stroke. The development of new subtype-specific antagonists would be of considerable therapeutic interest. Natural products can provide important new lead compounds for drug discovery. The only natural product known to inhibit glutamate receptors competitively is (-)-kaitocephalin, which was isolated from the fungus Eupenicillium shearii and found to protect CNS neurons from excitotoxicity. Previous work has shown that it is a potent antagonist of some subtypes of glutamate receptors (AMPA and NMDA, but not kainate). The structure of kaitocephalin bound to the ligand binding domain of the AMPA receptor subtype, GluA2, is reported here. The structure suggests how kaitocephalin can be used as a scaffold to develop more selective and high affinity antagonists for glutamate receptors.

PubMed: 23076153
DOI: 10.1074/jbc.M112.416362

Experimental method

X-RAY DIFFRACTION (1.9634 Å)