4DLD

Crystal structure of the GluK1 ligand-binding domain (S1S2) in complex with the antagonist (S)-2-amino-3-(2-(2-carboxyethyl)-5-chloro-4-nitrophenyl)propionic acid at 2.0 A resolution

Summary for 4DLD

• Entry DOI: 10.2210/pdb4dld/pdb
• Related: 3TZA
• Descriptor: Glutamate receptor, ionotropic kainate 1, (S)-2-amino-3-(2-(2-carboxyethyl)-5-chloro-4-nitrophenyl)propionic acid, CHLORIDE ION, ... (6 entities in total)
• Functional Keywords: ionotropic glutamate receptor, glutamate, membrane, membrane protein
• Biological source: Rattus norvegicus (rat); More
• Cellular location: Cell membrane; Multi-pass membrane protein: P22756
• Total number of polymer chains: 2
• Total formula weight: 59073.90

Authors

Venskutonyte, R.,Frydenvang, K.,Kastrup, J.S. (deposition date: 2012-02-06, release date: 2012-10-10, Last modification date: 2024-10-30)

Primary citation

Venskutonyte, R.,Frydenvang, K.,Valades, E.A.,Szymanska, E.,Johansen, T.N.,Kastrup, J.S.,Pickering, D.S.
Structural and pharmacological characterization of phenylalanine-based AMPA receptor antagonists at kainate receptors
Chemmedchem, 7:1793-1798, 2012

PubMed Abstract: Continued efforts into the discovery of ligands that target ionotropic glutamate receptors (iGluRs) are important for studies of the physiological roles of the various iGluR subtypes as well as for the search for drugs that can be used in the treatment of diseases of the central nervous system. A new series of phenylalanine derivatives that target iGluRs was reported to bind AMPA receptors. Herein we report our studies of these compounds at the kainate receptors GluK1-3. Several compounds bind with micromolar affinity at GluK1 and GluK3, but do not bind GluK2. The crystal structure of the most potent compound in the ligand binding domain of GluK1 revealed different modes of binding to GluK1 and GluA2, due primarily to residues Ser741 (GluK1) and Met729 (GluA2). The compound was shown to be slightly more potent at GluK1 than at AMPA receptors and to induce a domain closure similar to that observed in GluK1 structures with partial agonists.

PubMed: 22407805
DOI: 10.1002/cmdc.201100599

Experimental method

X-RAY DIFFRACTION (2 Å)