4IGR
Crystal structure of the kainate receptor GluK3 ligand-binding domain in complex with the agonist ZA302
Summary for 4IGR
| Entry DOI | 10.2210/pdb4igr/pdb |
| Related | 3S9E 4IGT |
| Descriptor | Glutamate receptor, ionotropic kainate 3, (4R)-4-{3-[hydroxy(methyl)amino]-3-oxopropyl}-L-glutamic acid, POTASSIUM ION, ... (6 entities in total) |
| Functional Keywords | membrane protein, ionotropic glutamate receptor, kainate receptor, ligand-binding domain, agonist |
| Biological source | Rattus norvegicus (rat) More |
| Cellular location | Cell membrane; Multi-pass membrane protein: P42264 |
| Total number of polymer chains | 1 |
| Total formula weight | 29549.31 |
| Authors | Larsen, A.P.,Venskutonyte, R.,Gajhede, M.,Kastrup, J.S.,Frydenvang, K. (deposition date: 2012-12-18, release date: 2013-03-06, Last modification date: 2024-10-30) |
| Primary citation | Assaf, Z.,Larsen, A.P.,Venskutonyte, R.,Han, L.,Abrahamsen, B.,Nielsen, B.,Gajhede, M.,Kastrup, J.S.,Jensen, A.A.,Pickering, D.S.,Frydenvang, K.,Gefflaut, T.,Bunch, L. Chemoenzymatic synthesis of new 2,4-syn-functionalized (S)-glutamate analogues and structure-activity relationship studies at ionotropic glutamate receptors and excitatory amino acid transporters. J.Med.Chem., 56:1614-1628, 2013 Cited by PubMed Abstract: In the mammalian central nervous system, (S)-glutamate (Glu) is released from the presynaptic neuron where it activates a plethora of pre- and postsynaptic Glu receptors. The fast acting ionotropic Glu receptors (iGluRs) are ligand gated ion channels and are believed to be involved in a vast number of neurological functions such as memory and learning, synaptic plasticity, and motor function. The synthesis of 14 enantiopure 2,4-syn-Glu analogues 2b-p is accessed by a short and efficient chemoenzymatic approach starting from readily available cyclohexanone 3. Pharmacological characterization at the iGluRs and EAAT1-3 subtypes revealed analogue 2i as a selective GluK1 ligand with low nanomolar affinity. Two X-ray crystal structures of the key analogue 2i in the ligand-binding domain (LBD) of GluA2 and GluK3 were determined. Partial domain closure was seen in the GluA2-LBD complex with 2i comparable to that induced by kainate. In contrast, full domain closure was observed in the GluK3-LBD complex with 2i, similar to that of GluK3-LBD with glutamate bound. PubMed: 23414088DOI: 10.1021/jm301433m PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.65 Å) |
Structure validation
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