8R32

Crystal structure of the GluK2 ligand-binding domain in complex with L-glutamate and BPAM344 at 1.60 A resolution

Summary for 8R32

• Entry DOI: 10.2210/pdb8r32/pdb
• Descriptor: Glutamate receptor ionotropic, kainate 2, GLUTAMIC ACID, 4-cyclopropyl-7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide, ... (6 entities in total)
• Functional Keywords: ionotropic glutamate receptor, gluk2 ligand-binding domain, membrane protein, positive allosteric modulator, l-glutamate
• Biological source: Rattus norvegicus (Norway rat); More
• Total number of polymer chains: 2
• Total formula weight: 59474.62

Authors

Bay, Y.,Jeppesen, M.E.,Frydenvang, K.,Kastrup, J.S. (deposition date: 2023-11-08, release date: 2024-09-18, Last modification date: 2024-11-06)

Primary citation

Bay, Y.,Egeberg Jeppesen, M.,Frydenvang, K.,Francotte, P.,Pirotte, B.,Pickering, D.S.,Kristensen, A.S.,Kastrup, J.S.
The positive allosteric modulator BPAM344 and L-glutamate introduce an active-like structure of the ligand-binding domain of GluK2.
Febs Lett., 598:743-757, 2024

PubMed Abstract: Kainate receptors belong to the family of ionotropic glutamate receptors and contribute to the majority of fast excitatory neurotransmission. Consequently, they also play a role in brain diseases. Therefore, understanding how these receptors can be modulated is of importance. Our study provides a crystal structure of the dimeric ligand-binding domain of the kainate receptor GluK2 in complex with L-glutamate and the small-molecule positive allosteric modulator, BPAM344, in an active-like conformation. The role of Thr535 and Gln786 in modulating GluK2 by BPAM344 was investigated using a calcium-sensitive fluorescence-based assay on transiently transfected cells expressing GluK2 and mutants hereof. This study may aid in the design of compounds targeting kainate receptors, expanding their potential as targets for the treatment of brain diseases.

PubMed: 38369668
DOI: 10.1002/1873-3468.14824

Experimental method

X-RAY DIFFRACTION (1.6 Å)