5un1
From Proteopedia
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== Function == | == Function == | ||
[[http://www.uniprot.org/uniprot/NMDZ1_XENLA 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).<ref>PMID:16214956</ref> <ref>PMID:19524674</ref> <ref>PMID:21677647</ref> <ref>PMID:25008524</ref> <ref>PMID:26912815</ref> <ref>PMID:27135925</ref> <ref>PMID:28232581</ref> [PDB:5IOV] | [[http://www.uniprot.org/uniprot/NMDZ1_XENLA 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).<ref>PMID:16214956</ref> <ref>PMID:19524674</ref> <ref>PMID:21677647</ref> <ref>PMID:25008524</ref> <ref>PMID:26912815</ref> <ref>PMID:27135925</ref> <ref>PMID:28232581</ref> [PDB:5IOV] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The NMDA (N-methyl-D-aspartate) receptor transduces the binding of glutamate and glycine, coupling it to the opening of a calcium-permeable ion channel (1) . Owing to the lack of high-resolution structural studies of the NMDA receptor, the mechanism by which ion-channel blockers occlude ion permeation is not well understood. Here we show that removal of the amino-terminal domains from the GluN1-GluN2B NMDA receptor yields a functional receptor and crystals with good diffraction properties, allowing us to map the binding site of the NMDA receptor blocker, MK-801. This crystal structure, together with long-timescale molecular dynamics simulations, shows how MK-801 and memantine (a drug approved for the treatment of Alzheimer's disease) bind within the vestibule of the ion channel, promote closure of the ion channel gate and lodge between the M3-helix-bundle crossing and the M2-pore loops, physically blocking ion permeation. | ||
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| + | Mechanism of NMDA receptor channel block by MK-801 and memantine.,Song X, Jensen MO, Jogini V, Stein RA, Lee CH, Mchaourab HS, Shaw DE, Gouaux E Nature. 2018 Apr;556(7702):515-519. doi: 10.1038/s41586-018-0039-9. Epub 2018 Apr, 18. PMID:29670280<ref>PMID:29670280</ref> | ||
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| + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
| + | </div> | ||
| + | <div class="pdbe-citations 5un1" style="background-color:#fffaf0;"></div> | ||
== References == | == References == | ||
<references/> | <references/> | ||
Revision as of 08:25, 2 May 2018
Crystal structure of GluN1/GluN2B delta-ATD NMDA receptor
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