3BFU

Structure of the ligand-binding core of GluR2 in complex with the agonist (R)-TDPA at 1.95 A resolution

Summary for 3BFU

• Entry DOI: 10.2210/pdb3bfu/pdb
• Related: 1FTM 3BFT
• Descriptor: Glutamate receptor 2, (2R)-2-amino-3-(4-hydroxy-1,2,5-thiadiazol-3-yl)propanoic acid (3 entities in total)
• Functional Keywords: ampa receptor, glur2, ligand-binding core, agonist, (r)-tdpa, alternative splicing, cell junction, endoplasmic reticulum, glycoprotein, ion transport, ionic channel, lipoprotein, membrane, palmitate, phosphoprotein, postsynaptic cell membrane, rna editing, synapse, transmembrane, transport, membrane protein
• Biological source: Rattus norvegicus (Rat); More
• Cellular location: Cell membrane; Multi-pass membrane protein: P19491
• Total number of polymer chains: 4
• Total formula weight: 117643.50

Authors

Beich-Frandsen, M.,Mirza, O.,Vestergaard, B.,Gajhede, M.,Kastrup, J.S. (deposition date: 2007-11-23, release date: 2008-10-14, Last modification date: 2024-10-16)

Primary citation

Beich-Frandsen, M.,Pickering, D.S.,Mirza, O.,Johansen, T.N.,Greenwood, J.,Vestergaard, B.,Schousboe, A.,Gajhede, M.,Liljefors, T.,Kastrup, J.S.
Structures of the ligand-binding core of iGluR2 in complex with the agonists (R)- and (S)-2-amino-3-(4-hydroxy-1,2,5-thiadiazol-3-yl)propionic acid explain their unusual equipotency.
J.Med.Chem., 51:1459-1463, 2008

PubMed Abstract: AMPA-type ionotropic glutamate receptors generally display high stereoselectivity in agonist binding. However, the stereoisomers of 2-amino-3-(4-hydroxy-1,2,5-thiadiazol-3-yl)propionic acid (TDPA) have similar enantiopharmacology. To understand this observation, we have determined the X-ray structures of ( R)-TDPA and ( S)-TDPA in complex with the ligand-binding core of iGluR2 and investigated the binding pharmacology at AMPA and kainate receptors. Both enantiomers induce full domain closure in iGluR2 but adopt different conformations when binding to the receptor, which may explain the similar enantiopharmacology.

PubMed: 18269227
DOI: 10.1021/jm701126w

Experimental method

X-RAY DIFFRACTION (1.95 Å)