6e7t: Difference between revisions

Latest revision as of 06:20, 11 October 2023

Heterodimer of the GluN1b-GluN2B NMDA receptor amino-terminal domains bound to allosteric inhibitor 93-6

Structural highlights

6e7t is a 4 chain structure with sequence from Rattus norvegicus and Xenopus laevis. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	X-ray diffraction, Resolution 2.31Å
Ligands:	BMA, CL, HYY, MAN, NA, NAG
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]

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:https://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:https://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:https://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:https://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:https://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:https://dx.doi.org/10.1126/science.aal3729

Proteopedia Page Contributors and Editors (what is this?)

OCA

[1] 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:https://dx.doi.org/10.1124/mol.105.016840

[2] 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:https://dx.doi.org/10.1016/j.mcn.2009.06.004

[3] 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

[4] 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:https://dx.doi.org/10.1038/nature13548

[5] 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:https://dx.doi.org/10.1124/mol.115.103036

[6] 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:https://dx.doi.org/10.1038/nature17679

[7] 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:https://dx.doi.org/10.1126/science.aal3729

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[2]

[3]

[4]

[5]

[6]

[7]

@@ Line 3: / Line 3: @@
 <StructureSection load='6e7t' size='340' side='right'caption='[[6e7t]], [[Resolution|resolution]] 2.31&Aring;' scene=''>
 == Structural highlights ==
-<table><tr><td colspan='2'>[[6e7t]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/African_clawed_frog African clawed frog] and [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E7T OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6E7T FirstGlance]. <br>
+<table><tr><td colspan='2'>[[6e7t]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] and [https://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6E7T OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=6E7T FirstGlance]. <br>
-</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=HYY:N-{4-[(2S)-3-{[2-(3,4-dichlorophenyl)ethyl](propyl)amino}-2-hydroxypropoxy]phenyl}methanesulfonamide'>HYY</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
+</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.31&#8491;</td></tr>
-<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">grin1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=8355 African clawed frog]), Grin2b ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BMA:BETA-D-MANNOSE'>BMA</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=HYY:N-{4-[(2S)-3-{[2-(3,4-dichlorophenyl)ethyl](propyl)amino}-2-hydroxypropoxy]phenyl}methanesulfonamide'>HYY</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6e7t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e7t OCA], [http://pdbe.org/6e7t PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6e7t RCSB], [http://www.ebi.ac.uk/pdbsum/6e7t PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6e7t ProSAT]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=6e7t FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6e7t OCA], [https://pdbe.org/6e7t PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=6e7t RCSB], [https://www.ebi.ac.uk/pdbsum/6e7t PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=6e7t ProSAT]</span></td></tr>
 </table>
 == 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/NMDE2_RAT 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).
+[https://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]
 ==See Also==
@@ Line 17: / Line 17: @@
 __TOC__
 </StructureSection>
-[[Category: African clawed frog]]
-[[Category: Buffalo rat]]
 [[Category: Large Structures]]
-[[Category: Furukawa, H]]
+[[Category: Rattus norvegicus]]
-[[Category: Regan, M C]]
+[[Category: Xenopus laevis]]
-[[Category: Allosteric modulation]]
+[[Category: Furukawa H]]
-[[Category: Extracellular domain]]
+[[Category: Regan MC]]
-[[Category: Ion channel]]
-[[Category: Nmda receptor]]
-[[Category: Transport protein]]

6e7t: Difference between revisions

Latest revision as of 06:20, 11 October 2023

Heterodimer of the GluN1b-GluN2B NMDA receptor amino-terminal domains bound to allosteric inhibitor 93-6

Structural highlights

Function

See Also

References

Contents

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