4FAT
Ligand-binding domain of GluA2 (flip) ionotropic glutamate receptor in complex with an allosteric modulator
Summary for 4FAT
| Entry DOI | 10.2210/pdb4fat/pdb |
| Descriptor | Glutamate receptor 2, GLUTAMIC ACID, 2-({[4-(hydroxymethyl)-3-(trifluoromethyl)-1H-pyrazol-1-yl]acetyl}amino)-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide, ... (7 entities in total) |
| Functional Keywords | transport protein, ion channel, chimera protein, membrane protein |
| Biological source | Rattus norvegicus (brown rat,rat,rats) More |
| Cellular location | Cell membrane; Multi-pass membrane protein: P19491 |
| Total number of polymer chains | 1 |
| Total formula weight | 30390.70 |
| Authors | Maclean, J.K.F.,Kazemier, B. (deposition date: 2012-05-22, release date: 2012-07-11, Last modification date: 2024-11-20) |
| Primary citation | Harms, J.E.,Benveniste, M.,Maclean, J.K.,Partin, K.M.,Jamieson, C. Functional analysis of a novel positive allosteric modulator of AMPA receptors derived from a structure-based drug design strategy. Neuropharmacology, 64:45-52, 2013 Cited by PubMed Abstract: Positive allosteric modulators of α-amino-3-hydroxy-5-methyl-isoxazole-propionic acid (AMPA) receptors facilitate synaptic plasticity and can improve various forms of learning and memory. These modulators show promise as therapeutic agents for the treatment of neurological disorders such as schizophrenia, ADHD, and mental depression. Three classes of positive modulator, the benzamides, the thiadiazides, and the biarylsulfonamides differentially occupy a solvent accessible binding pocket at the interface between the two subunits that form the AMPA receptor ligand-binding pocket. Here, we describe the electrophysiological properties of a new chemotype derived from a structure-based drug design strategy (SBDD), which makes similar receptor interactions compared to previously reported classes of modulator. This pyrazole amide derivative, JAMI1001A, with a promising developability profile, efficaciously modulates AMPA receptor deactivation and desensitization of both flip and flop receptor isoforms. This article is part of a Special Issue entitled 'Cognitive Enhancers'. PubMed: 22735771DOI: 10.1016/j.neuropharm.2012.06.008 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.4 Å) |
Structure validation
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