| Structural highlights
6e7u is a 4 chain structure. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
| | Ligands: | , , , , , |
| Resources: | FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT |
Function
[NMDZ1_XENLA] Component of NMDA receptor complexes that function as heterotetrameric, ligand-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Channel activation requires binding of the neurotransmitter glutamate to the epsilon subunit, glycine binding to the zeta subunit, plus membrane depolarization to eliminate channel inhibition by Mg(2+) (PubMed:16214956, PubMed:19524674, PubMed:21677647, PubMed:25008524, PubMed:26912815, PubMed:27135925, Ref.11, PubMed:28232581). Sensitivity to glutamate and channel kinetics depend on the subunit composition (Probable).[1] [2] [3] [4] [5] [6] [7] [PDB:5IOV] [NMDE2_RAT] NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. In concert with DAPK1 at extrasynaptic sites, acts as a central mediator for stroke damage. Its phosphorylation at Ser-1303 by DAPK1 enhances synaptic NMDA receptor channel activity inducing injurious Ca2+ influx through them, resulting in an irreversible neuronal death (By similarity).
References
- ↑ Schmidt C, Werner M, Hollmann M. Revisiting the postulated "unitary glutamate receptor": electrophysiological and pharmacological analysis in two heterologous expression systems fails to detect evidence for its existence. Mol Pharmacol. 2006 Jan;69(1):119-29. doi: 10.1124/mol.105.016840. Epub 2005 Oct , 7. PMID:16214956 doi:http://dx.doi.org/10.1124/mol.105.016840
- ↑ Schmidt C, Hollmann M. Molecular and functional characterization of Xenopus laevis N-methyl-d-aspartate receptors. Mol Cell Neurosci. 2009 Oct;42(2):116-27. doi: 10.1016/j.mcn.2009.06.004. Epub, 2009 Jun 12. PMID:19524674 doi:http://dx.doi.org/10.1016/j.mcn.2009.06.004
- ↑ Karakas E, Simorowski N, Furukawa H. Subunit arrangement and phenylethanolamine binding in GluN1/GluN2B NMDA receptors. Nature. 2011 Jun 15;475(7355):249-53. doi: 10.1038/nature10180. PMID:21677647 doi:10.1038/nature10180
- ↑ Lee CH, Lu W, Michel JC, Goehring A, Du J, Song X, Gouaux E. NMDA receptor structures reveal subunit arrangement and pore architecture. Nature. 2014 Jul 10;511(7508):191-7. doi: 10.1038/nature13548. Epub 2014 Jun 22. PMID:25008524 doi:http://dx.doi.org/10.1038/nature13548
- ↑ Stroebel D, Buhl DL, Knafels JD, Chanda PK, Green M, Sciabola S, Mony L, Paoletti P, Pandit J. A novel binding mode reveals two distinct classes of NMDA receptor GluN2B-selective antagonists. Mol Pharmacol. 2016 Feb 24. pii: mol.115.103036. PMID:26912815 doi:http://dx.doi.org/10.1124/mol.115.103036
- ↑ Tajima N, Karakas E, Grant T, Simorowski N, Diaz-Avalos R, Grigorieff N, Furukawa H. Activation of NMDA receptors and the mechanism of inhibition by ifenprodil. Nature. 2016 May 2. doi: 10.1038/nature17679. PMID:27135925 doi:http://dx.doi.org/10.1038/nature17679
- ↑ Lu W, Du J, Goehring A, Gouaux E. Cryo-EM structures of the triheteromeric NMDA receptor and its allosteric modulation. Science. 2017 Feb 23. pii: eaal3729. doi: 10.1126/science.aal3729. PMID:28232581 doi:http://dx.doi.org/10.1126/science.aal3729
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