Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Positive and negative allosteric modulation of GluK2 kainate receptors by BPAM344 and antiepileptic perampanel.
Journal, issue, pages	Cell Rep, Vol. 42, Issue 2, Page 112124, Year 2023
Publish date	Feb 21, 2023
Authors	Shanti Pal Gangwar / Laura Y Yen / Maria V Yelshanskaya / Alexander I Sobolevsky /
PubMed Abstract	Kainate receptors (KARs) are a subtype of ionotropic glutamate receptors that control synaptic transmission in the central nervous system and are implicated in neurological, psychiatric, and ...Kainate receptors (KARs) are a subtype of ionotropic glutamate receptors that control synaptic transmission in the central nervous system and are implicated in neurological, psychiatric, and neurodevelopmental disorders. Understanding the regulation of KAR function by small molecules is essential for exploring these receptors as drug targets. Here, we present cryoelectron microscopy (cryo-EM) structures of KAR GluK2 in complex with the positive allosteric modulator BPAM344, competitive antagonist DNQX, and negative allosteric modulator, antiepileptic drug perampanel. Our structures show that two BPAM344 molecules bind per ligand-binding domain dimer interface. In the absence of an agonist or in the presence of DNQX, BPAM344 stabilizes GluK2 in the closed state. The closed state is also stabilized by perampanel, which binds to the ion channel extracellular collar sites located in two out of four GluK2 subunits. The molecular mechanisms of positive and negative allosteric modulation of KAR provide a guide for developing new therapeutic strategies.
External links	Cell Rep / PubMed:36857176 / PubMed Central
Methods	EM (single particle)
Resolution	3.03 - 3.96 Å
Structure data	29515 8fwq EMDB-29515, PDB-8fwq: Structure of kainate receptor GluK2 in complex with the positive allosteric modulator BPAM344 Method: EM (single particle) / Resolution: 3.96 Å 29516 8fwr EMDB-29516, PDB-8fwr: Structure of the amino-terminal domain of kainate receptor GluK2 in complex with the positive allosteric modulator BPAM344 Method: EM (single particle) / Resolution: 3.1 Å 29517 8fws EMDB-29517, PDB-8fws: Structure of the ligand-binding and transmembrane domains of kainate receptor GluK2 in complex with the positive allosteric modulator BPAM344 Method: EM (single particle) / Resolution: 3.23 Å 29518 8fwt EMDB-29518, PDB-8fwt: Structure of the amino terminal domain of kainate receptor GluK2 in complex with the positive allosteric modulator BPAM344 and competitive antagonist DNQX Method: EM (single particle) / Resolution: 3.09 Å 29519 8fwu EMDB-29519, PDB-8fwu: Structure of the ligand-binding and transmembrane domains of kainate receptor GluK2 in complex with the positive allosteric modulator BPAM344 and competitive antagonist DNQX Method: EM (single particle) / Resolution: 3.18 Å 29520 8fwv EMDB-29520, PDB-8fwv: Structure of the amino-terminal domain of kainate receptor GluK2 in complex with the positive allosteric modulator BPAM344 and noncompetitive inhibitor perampanel Method: EM (single particle) / Resolution: 3.03 Å 29521 8fww EMDB-29521, PDB-8fww: Structure of the ligand-binding and transmembrane domains of kainate receptor GluK2 in complex with the positive allosteric modulator BPAM344 and noncompetitive inhibitor perampanel Method: EM (single particle) / Resolution: 3.1 Å
Chemicals	ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose ChemComp-2J9: 4-cyclopropyl-7-fluoro-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide ChemComp-NA: Unknown entry ChemComp-POV: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / phospholipidYM ChemComp-CL: Unknown entry ChemComp-DNQ: 6,7-DINITROQUINOXALINE-2,3-DIONE / antagonistYM ChemComp-HOH: WATER ChemComp-6ZP: 2-(6'-oxo-1'-phenyl[1',6'-dihydro[2,3'-bipyridine]]-5'-yl)benzonitrile / medication*YM
Source	rattus norvegicus (Norway rat)
Keywords	MEMBRANE PROTEIN / ion channel / iGluR / Kainate receptor / positive allosteric modulator / DNQX / Perampanel