3qem - Revision history

OCA at 11:43, 14 March 2024

2024-03-14T11:43:09Z

←Older revision		Revision as of 11:43, 14 March 2024
Line 3:		Line 3:
	<StructureSection load='3qem' size='340' side='right'caption='[[3qem]], [[Resolution\|resolution]] 3.00Å' scene=''>		<StructureSection load='3qem' size='340' side='right'caption='[[3qem]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3qem]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/~~African_clawed_frog African clawed frog~~] and [https://en.wikipedia.org/wiki/~~Buffalo_rat Buffalo rat~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QEM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QEM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3qem]] 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=3QEM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QEM FirstGlance]. <br>
-	</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=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=QEM:4-[(1R,2S)-3-(4-BENZYLPIPERIDIN-1-YL)-1-HYDROXY-2-METHYLPROPYL]PHENOL'>QEM</scene>~~, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</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]] 3.003Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3jpw\|3jpw]], [[3qek\|3qek]], [[3qel\|3qel]]</div></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=MAN:ALPHA-D-MANNOSE'>MAN</scene>, <scene name='pdbligand=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=QEM:4-[(1R,2S)-3-(4-BENZYLPIPERIDIN-1-YL)-1-HYDROXY-2-METHYLPROPYL]PHENOL'>QEM</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">grin1, NR1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=8355 African clawed frog]), Grin2b ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=3qem FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qem OCA], [https://pdbe.org/3qem PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qem RCSB], [https://www.ebi.ac.uk/pdbsum/3qem PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qem 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=3qem FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qem OCA], [https://pdbe.org/3qem PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qem RCSB], [https://www.ebi.ac.uk/pdbsum/3qem PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qem ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://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]
-	~~<div style="background-color:#fffaf0;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	~~Since it was discovered that~~ the ~~anti-hypertensive agent ifenprodil has neuroprotective activity through its effects on NMDA (N-methyl-D-aspartate) receptors, a determined effort has been made~~ to ~~understand~~ the mechanism of action and to develop improved therapeutic compounds on the basis of this knowledge. Neurotransmission mediated by NMDA receptors is essential for basic brain development and function. These receptors form heteromeric ion channels and become activated after concurrent binding ~~of glycine and glutamate~~ to the ~~GluN1 and GluN2 subunits~~, ~~respectively. A functional hallmark of NMDA receptors is that their ion-~~channel ~~activity is allosterically regulated~~ by ~~binding of small compounds to the amino-terminal domain~~ (~~ATD~~) ~~in a subtype-specific manner. Ifenprodil and related phenylethanolamine compounds~~, ~~which specifically inhibit GluN1 and GluN2B NMDA receptors~~, ~~have been intensely studied for their potential use in the treatment of various neurological disorders and diseases~~, ~~including depression~~, ~~Alzheimer's disease and Parkinson's disease. Despite considerable enthusiasm~~, ~~mechanisms underlying the recognition of phenylethanolamines and ATD-mediated allosteric inhibition remain limited owing to a lack of structural information~~. ~~Here we report that the GluN1 and GluN2B ATDs form a heterodimer and that phenylethanolamine binds at the interface between GluN1 and GluN2B~~, ~~rather than within the GluN2B cleft~~. ~~The crystal structure of the heterodimer formed between the GluN1b ATD from Xenopus laevis~~ and the ~~GluN2B ATD from Rattus norvegicus shows a highly distinct pattern of~~ subunit arrangement that is different from the arrangements observed in homodimeric non-NMDA receptors and reveals the molecular determinants for phenylethanolamine binding. Restriction of domain movement in the bi-lobed structure of the GluN2B ATD, by engineering of an inter-subunit disulphide bond, markedly decreases sensitivity to ifenprodil, indicating that conformational freedom in the GluN2B ATD is essential for ifenprodil-mediated allosteric inhibition of NMDA receptors. These findings pave the way for improving the design of subtype-specific compounds with therapeutic value for neurological disorders and diseases.	+
-		+
-	~~Subunit arrangement and phenylethanolamine binding in GluN1/GluN2B NMDA receptors.,Karakas E, Simorowski N, Furukawa H Nature. 2011 Jun 15;475~~(~~7355~~)~~:249-53~~. ~~doi~~: ~~10.1038~~/~~nature10180.~~ PMID:~~21677647~~<ref>PMID:21677647</ref>	+
-		+
-	~~From MEDLINE®~~/~~PubMed®, a database of the U.S. National Library of Medicine.~~<br>	+
-	</~~div~~>	+
-	<~~div class="pdbe-citations 3qem" style="background-color~~:~~#fffaf0;"~~></~~div~~>	+

	==See Also==		==See Also==
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	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: African clawed frog]]
-	[[Category: Buffalo rat]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Furukawa, H~~]]	+	[[Category: Rattus norvegicus]]
-	[[Category: ~~Karakas, E~~]]	+	[[Category: Xenopus laevis]]
-	[[Category: ~~Simorowski, N~~]]	+	[[Category: Furukawa H]]
-	[[Category: ~~Allosteric modulation]]~~	+	[[Category: Karakas E]]
-	~~[[Category: Extracellular]]~~	+	[[Category: Simorowski N]]
-	~~[[Category: Ion channel~~]]	+
-	[[Category: N~~-glycosylation]]~~	+
-	~~[[Category: Nmda receptor]]~~	+
-	~~[[Category: Phenylethanolamine]]~~	+
-	~~[[Category: Transmembrane]]~~	+
-	~~[[Category: Transport protein~~]]	+

OCA at 06:05, 8 June 2022

2022-06-08T06:05:29Z

←Older revision		Revision as of 06:05, 8 June 2022
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	==Crystal structure of amino terminal domains of the NMDA receptor subunit GluN1 and GluN2B in complex with Ro 25-6981==		==Crystal structure of amino terminal domains of the NMDA receptor subunit GluN1 and GluN2B in complex with Ro 25-6981==
-	<StructureSection load='3qem' size='340' side='right' caption='[[3qem]], [[Resolution\|resolution]] 3.00Å' scene=''>	+	<StructureSection load='3qem' size='340' side='right'caption='[[3qem]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3qem]] 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=3QEM OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3QEM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3qem]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/African_clawed_frog African clawed frog] and [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QEM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3QEM 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=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=QEM:4-[(1R,2S)-3-(4-BENZYLPIPERIDIN-1-YL)-1-HYDROXY-2-METHYLPROPYL]PHENOL'>QEM</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>	+	</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=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=QEM:4-[(1R,2S)-3-(4-BENZYLPIPERIDIN-1-YL)-1-HYDROXY-2-METHYLPROPYL]PHENOL'>QEM</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3jpw\|3jpw]], [[3qek\|3qek]], [[3qel\|3qel]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[3jpw\|3jpw]], [[3qek\|3qek]], [[3qel\|3qel]]</div></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">grin1, NR1 ([~~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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">grin1, NR1 ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=8355 African clawed frog]), Grin2b ([https://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Buffalo rat])</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=3qem FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qem OCA], [~~http~~://pdbe.org/3qem PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3qem RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3qem PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3qem 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=3qem FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qem OCA], [https://pdbe.org/3qem PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3qem RCSB], [https://www.ebi.ac.uk/pdbsum/3qem PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3qem ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[~~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/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).
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 22:

	==See Also==		==See Also==
-	*[[~~Ionotropic~~ Glutamate ~~Receptors~~\|~~Ionotropic~~ Glutamate ~~Receptors~~]]	+	*[[Glutamate receptor 3D structures\|Glutamate receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
Line 29:		Line 29:
	[[Category: African clawed frog]]		[[Category: African clawed frog]]
	[[Category: Buffalo rat]]		[[Category: Buffalo rat]]
		+	[[Category: Large Structures]]
	[[Category: Furukawa, H]]		[[Category: Furukawa, H]]
	[[Category: Karakas, E]]		[[Category: Karakas, E]]

OCA at 17:25, 4 August 2016

2016-08-04T17:25:39Z

←Older revision		Revision as of 17:25, 4 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of amino terminal domains of the NMDA receptor subunit GluN1 and GluN2B in complex with Ro 25-6981==		==Crystal structure of amino terminal domains of the NMDA receptor subunit GluN1 and GluN2B in complex with Ro 25-6981==
	<StructureSection load='3qem' size='340' side='right' caption='[[3qem]], [[Resolution\|resolution]] 3.00Å' scene=''>		<StructureSection load='3qem' size='340' side='right' caption='[[3qem]], [[Resolution\|resolution]] 3.00Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3qem]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Rattus_norvegicus Rattus norvegicus~~] and [http://en.wikipedia.org/wiki/~~Xenopus_laevis Xenopus laevis~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QEM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QEM FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3qem]] 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=3QEM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QEM 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=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=QEM:4-[(1R,2S)-3-(4-BENZYLPIPERIDIN-1-YL)-1-HYDROXY-2-METHYLPROPYL]PHENOL'>QEM</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>		</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=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=QEM:4-[(1R,2S)-3-(4-BENZYLPIPERIDIN-1-YL)-1-HYDROXY-2-METHYLPROPYL]PHENOL'>QEM</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3jpw\|3jpw]], [[3qek\|3qek]], [[3qel\|3qel]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3jpw\|3jpw]], [[3qek\|3qek]], [[3qel\|3qel]]</td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">grin1, NR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=8355 ~~Xenopus laevis~~]), Grin2b ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 ~~Rattus norvegicus~~])</td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">grin1, NR1 ([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='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=3qem FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qem OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qem RCSB], [http://www.ebi.ac.uk/pdbsum/3qem PDBsum]</span></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=3qem FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qem OCA], [http://pdbe.org/3qem PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3qem RCSB], [http://www.ebi.ac.uk/pdbsum/3qem PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3qem ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
Line 18:		Line 19:
	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>		From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
	</div>		</div>
		+	<div class="pdbe-citations 3qem" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 25:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Rattus norvegicus~~]]	+	[[Category: African clawed frog]]
-	[[Category: ~~Xenopus laevis~~]]	+	[[Category: Buffalo rat]]
	[[Category: Furukawa, H]]		[[Category: Furukawa, H]]
	[[Category: Karakas, E]]		[[Category: Karakas, E]]

OCA at 11:23, 25 December 2014

2014-12-25T11:23:23Z

←Older revision		Revision as of 11:23, 25 December 2014
Line 8:		Line 8:
	<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=3qem FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qem OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qem RCSB], [http://www.ebi.ac.uk/pdbsum/3qem PDBsum]</span></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=3qem FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qem OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qem RCSB], [http://www.ebi.ac.uk/pdbsum/3qem PDBsum]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[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).
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 11:32, 9 December 2014

2014-12-09T11:32:07Z

←Older revision		Revision as of 11:32, 9 December 2014
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-	[[~~Image:~~3qem.~~png~~\|~~left~~\|~~200px~~]]	+	==Crystal structure of amino terminal domains of the NMDA receptor subunit GluN1 and GluN2B in complex with Ro 25-6981==
		+	<StructureSection load='3qem' size='340' side='right' caption='[[3qem]], [[Resolution\|resolution]] 3.00Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3qem]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] and [http://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QEM OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3QEM 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=NA:SODIUM+ION'>NA</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=QEM:4-[(1R,2S)-3-(4-BENZYLPIPERIDIN-1-YL)-1-HYDROXY-2-METHYLPROPYL]PHENOL'>QEM</scene>, <scene name='pdbligand=MAN:ALPHA-D-MANNOSE'>MAN</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[3jpw\|3jpw]], [[3qek\|3qek]], [[3qel\|3qel]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">grin1, NR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=8355 Xenopus laevis]), Grin2b ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10116 Rattus norvegicus])</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=3qem FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3qem OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3qem RCSB], [http://www.ebi.ac.uk/pdbsum/3qem PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Since it was discovered that the anti-hypertensive agent ifenprodil has neuroprotective activity through its effects on NMDA (N-methyl-D-aspartate) receptors, a determined effort has been made to understand the mechanism of action and to develop improved therapeutic compounds on the basis of this knowledge. Neurotransmission mediated by NMDA receptors is essential for basic brain development and function. These receptors form heteromeric ion channels and become activated after concurrent binding of glycine and glutamate to the GluN1 and GluN2 subunits, respectively. A functional hallmark of NMDA receptors is that their ion-channel activity is allosterically regulated by binding of small compounds to the amino-terminal domain (ATD) in a subtype-specific manner. Ifenprodil and related phenylethanolamine compounds, which specifically inhibit GluN1 and GluN2B NMDA receptors, have been intensely studied for their potential use in the treatment of various neurological disorders and diseases, including depression, Alzheimer's disease and Parkinson's disease. Despite considerable enthusiasm, mechanisms underlying the recognition of phenylethanolamines and ATD-mediated allosteric inhibition remain limited owing to a lack of structural information. Here we report that the GluN1 and GluN2B ATDs form a heterodimer and that phenylethanolamine binds at the interface between GluN1 and GluN2B, rather than within the GluN2B cleft. The crystal structure of the heterodimer formed between the GluN1b ATD from Xenopus laevis and the GluN2B ATD from Rattus norvegicus shows a highly distinct pattern of subunit arrangement that is different from the arrangements observed in homodimeric non-NMDA receptors and reveals the molecular determinants for phenylethanolamine binding. Restriction of domain movement in the bi-lobed structure of the GluN2B ATD, by engineering of an inter-subunit disulphide bond, markedly decreases sensitivity to ifenprodil, indicating that conformational freedom in the GluN2B ATD is essential for ifenprodil-mediated allosteric inhibition of NMDA receptors. These findings pave the way for improving the design of subtype-specific compounds with therapeutic value for neurological disorders and diseases.

-	~~{{STRUCTURE_3qem\| PDB=3qem \| SCENE= }}~~	+	Subunit arrangement and phenylethanolamine binding in GluN1/GluN2B NMDA receptors.,Karakas E, Simorowski N, Furukawa H Nature. 2011 Jun 15;475(7355):249-53. doi: 10.1038/nature10180. PMID:21677647<ref>PMID:21677647</ref>

-	~~===Crystal structure of amino terminal domains~~ of the ~~NMDA receptor subunit GluN1 and GluN2B in complex with Ro 25-6981===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_21677647}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[3qem]] is a 4 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org/wiki/Rattus_norvegicus Rattus norvegicus] and [http://en~~.~~wikipedia.org~~/~~wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QEM OCA].~~	+

	==See Also==		==See Also==
	*[[Ionotropic Glutamate Receptors\|Ionotropic Glutamate Receptors]]		*[[Ionotropic Glutamate Receptors\|Ionotropic Glutamate Receptors]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:021677647<~~/~~ref~~><~~references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Rattus norvegicus]]		[[Category: Rattus norvegicus]]
	[[Category: Xenopus laevis]]		[[Category: Xenopus laevis]]
-	[[Category: Furukawa, H.]]	+	[[Category: Furukawa, H]]
-	[[Category: Karakas, E.]]	+	[[Category: Karakas, E]]
-	[[Category: Simorowski, N.]]	+	[[Category: Simorowski, N]]
	[[Category: Allosteric modulation]]		[[Category: Allosteric modulation]]
	[[Category: Extracellular]]		[[Category: Extracellular]]

OCA at 16:07, 20 October 2012

2012-10-20T16:07:19Z

←Older revision		Revision as of 16:07, 20 October 2012
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	==About this Structure==		==About this Structure==
-	[[3qem]] is a 4 chain structure ~~of [[Ionotropic Glutamate Receptors]]~~ with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] and [http://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QEM OCA].	+	[[3qem]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] and [http://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QEM OCA].

	==See Also==		==See Also==

OCA at 20:40, 26 July 2012

2012-07-26T20:40:22Z

←Older revision		Revision as of 20:40, 26 July 2012
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	[[Image:3qem.png\|left\|200px]]		[[Image:3qem.png\|left\|200px]]

-	<!--
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-	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
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-	-->
	{{STRUCTURE_3qem\| PDB=3qem \| SCENE= }}		{{STRUCTURE_3qem\| PDB=3qem \| SCENE= }}

	===Crystal structure of amino terminal domains of the NMDA receptor subunit GluN1 and GluN2B in complex with Ro 25-6981===		===Crystal structure of amino terminal domains of the NMDA receptor subunit GluN1 and GluN2B in complex with Ro 25-6981===

-
-	<!--
-	The line below this paragraph, {{ABSTRACT_PUBMED_21677647}}, adds the Publication Abstract to the page
-	(as it appears on PubMed at http://www.pubmed.gov), where 21677647 is the PubMed ID number.
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	{{ABSTRACT_PUBMED_21677647}}		{{ABSTRACT_PUBMED_21677647}}

	==About this Structure==		==About this Structure==
-	[[3qem]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] and [http://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QEM OCA].	+	[[3qem]] is a 4 chain structure of [[Ionotropic Glutamate Receptors]] with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] and [http://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QEM OCA].
		+
		+	==See Also==
		+	*[[Ionotropic Glutamate Receptors\|Ionotropic Glutamate Receptors]]

	==Reference==		==Reference==

OCA at 05:18, 20 July 2011

2011-07-20T05:18:43Z

←Older revision		Revision as of 05:18, 20 July 2011
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-	[[Image:3qem.~~jpg~~\|left\|200px]]	+	[[Image:3qem.png\|left\|200px]]

	<!--		<!--
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	===Crystal structure of amino terminal domains of the NMDA receptor subunit GluN1 and GluN2B in complex with Ro 25-6981===		===Crystal structure of amino terminal domains of the NMDA receptor subunit GluN1 and GluN2B in complex with Ro 25-6981===

		+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_21677647}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 21677647 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_21677647}}

	==About this Structure==		==About this Structure==
	[[3qem]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] and [http://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QEM OCA].		[[3qem]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] and [http://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QEM OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:021677647</ref><references group="xtra"/>
	[[Category: Rattus norvegicus]]		[[Category: Rattus norvegicus]]
	[[Category: Xenopus laevis]]		[[Category: Xenopus laevis]]

OCA at 06:32, 15 June 2011

2011-06-15T06:32:38Z

←Older revision		Revision as of 06:32, 15 June 2011
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-	~~'''Unreleased structure'''~~	+	[[Image:3qem.jpg\|left\|200px]]

-	The ~~entry 3qem~~ is ~~ON HOLD~~ ~~until Paper Publication~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3qem", creates the "Structure Box" on the page.
		+	You may change the PDB parameter (which sets the PDB file loaded into the applet)
		+	or the SCENE parameter (which sets the initial scene displayed when the page is loaded),
		+	or leave the SCENE parameter empty for the default display.
		+	-->
		+	{{STRUCTURE_3qem\| PDB=3qem \| SCENE= }}

-	~~Authors: Karakas, E., Simorowski, N., Furukawa, H.~~	+	===Crystal structure of amino terminal domains of the NMDA receptor subunit GluN1 and GluN2B in complex with Ro 25-6981===

-	~~Description~~:	+
		+	==About this Structure==
		+	[[3qem]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus] and [http://en.wikipedia.org/wiki/Xenopus_laevis Xenopus laevis]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3QEM OCA].
		+	[[Category: Rattus norvegicus]]
		+	[[Category: Xenopus laevis]]
		+	[[Category: Furukawa, H.]]
		+	[[Category: Karakas, E.]]
		+	[[Category: Simorowski, N.]]
		+	[[Category: Allosteric modulation]]
		+	[[Category: Extracellular]]
		+	[[Category: Ion channel]]
		+	[[Category: N-glycosylation]]
		+	[[Category: Nmda receptor]]
		+	[[Category: Phenylethanolamine]]
		+	[[Category: Transmembrane]]
		+	[[Category: Transport protein]]

OCA at 04:46, 8 June 2011

2011-06-08T04:46:17Z

←Older revision		Revision as of 04:46, 8 June 2011
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	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 3qem is ON HOLD	+	The entry 3qem is ON HOLD until Paper Publication

	Authors: Karakas, E., Simorowski, N., Furukawa, H.		Authors: Karakas, E., Simorowski, N., Furukawa, H.

	Description:		Description: