2P2A

X-ray structure of the GluR2 ligand binding core (S1S2J) in complex with 2-Bn-tet-AMPA at 2.26A resolution

Summary for 2P2A

• Entry DOI: 10.2210/pdb2p2a/pdb
• Related: 1FTJ 1FTM 1M5B
• Descriptor: Glutamate receptor 2, SULFATE ION, GLUTAMIC ACID, ... (5 entities in total)
• Functional Keywords: ionotropic glutamate receptor glur2, ligand-binding core, agonist complex, membrane protein
• Biological source: Rattus norvegicus (Norway rat); More
• Cellular location: Cell membrane; Multi-pass membrane protein: P19491
• Total number of polymer chains: 2
• Total formula weight: 59208.98

Authors

Frydenvang, K.,Kastrup, J.S.,Gajhede, M. (deposition date: 2007-03-07, release date: 2007-06-19, Last modification date: 2024-11-20)

Primary citation

Vogensen, S.B.,Frydenvang, K.,Greenwood, J.R.,Postorino, G.,Nielsen, B.,Pickering, D.S.,Ebert, B.,Bolcho, U.,Egebjerg, J.,Gajhede, M.,Kastrup, J.S.,Johansen, T.N.,Clausen, R.P.,Krogsgaard-Larsen, P.
A tetrazolyl-substituted subtype-selective AMPA receptor agonist.
J.Med.Chem., 50:2408-2414, 2007

PubMed Abstract: Replacement of the methyl group of the AMPA receptor agonist 2-amino-3-[3-hydroxy-5-(2-methyl-2H-5-tetrazolyl)-4-isoxazolyl]propionic acid (2-Me-Tet-AMPA) with a benzyl group provided the first AMPA receptor agonist, compound 7, capable of discriminating GluR2-4 from GluR1 by its more than 10-fold preference for the former receptor subtypes. An X-ray crystallographic analysis of this new analogue in complex with the GluR2-S1S2J construct shows that accommodation of the benzyl group creates a previously unobserved pocket in the receptor, which may explain the remarkable pharmacological profile of compound 7.

PubMed: 17455929
DOI: 10.1021/jm061439q

Experimental method

X-RAY DIFFRACTION (2.26 Å)