5i2n - Revision history

OCA at 08:21, 23 August 2023

2023-08-23T08:21:05Z

←Older revision		Revision as of 08:21, 23 August 2023
Line 3:		Line 3:
	<StructureSection load='5i2n' size='340' side='right'caption='[[5i2n]], [[Resolution\|resolution]] 2.12Å' scene=''>		<StructureSection load='5i2n' size='340' side='right'caption='[[5i2n]], [[Resolution\|resolution]] 2.12Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5i2n]] is a 2 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Human Human~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I2N OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://proteopedia.org/fgij/fg.htm?mol=5I2N FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5i2n]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I2N OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5I2N FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=67J:N-ETHYL-7-{[2-FLUORO-3-(TRIFLUOROMETHYL)PHENYL]METHYL}-2-METHYL-5-OXO-5H-[1,3]THIAZOLO[3,2-A]PYRIMIDINE-3-CARBOXAMIDE'>67J</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=GLY:GLYCINE'>GLY</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]] 2.12Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5i2j\|5i2j]], [[5i2k\|5i2k]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=67J:N-ETHYL-7-{[2-FLUORO-3-(TRIFLUOROMETHYL)PHENYL]METHYL}-2-METHYL-5-OXO-5H-[1,3]THIAZOLO[3,2-A]PYRIMIDINE-3-CARBOXAMIDE'>67J</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=GLY:GLYCINE'>GLY</scene></td></tr>
-	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GRIN2A, NMDAR2A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GRIN1, NMDAR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</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=5i2n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i2n OCA], [https://pdbe.org/5i2n PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5i2n RCSB], [https://www.ebi.ac.uk/pdbsum/5i2n PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5i2n ProSAT]</span></td></tr>
-	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[~~http~~://proteopedia.org/fgij/fg.htm?mol=5i2n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i2n OCA], [~~http~~://pdbe.org/5i2n PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5i2n RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5i2n PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5i2n ProSAT]</span></td></tr>	+
	</table>		</table>
	== Disease ==		== Disease ==
-	[~~[http~~://www.uniprot.org/uniprot/NMDE1_HUMAN NMDE1_HUMAN]] Landau-Kleffner syndrome;Early-onset epileptic encephalopathy and intellectual disability due to GRIN2A mutation;Continuous spikes and waves during sleep;Rolandic epilepsy;Rolandic epilepsy - speech dyspraxia. The disease is caused by mutations affecting the gene represented in this entry. A chromosomal aberration involving GRIN2A has been found in a family with epilepsy and neurodevelopmental defects. Translocation t(16;17)(p13.2;q11.2). GRIN2A somatic mutations have been frequently found in cutaneous malignant melanoma, suggesting that the glutamate signaling pathway may play a role in the pathogenesis of melanoma.<ref>PMID:21499247</ref> <ref>PMID:24455489</ref> [[http://www.uniprot.org/uniprot/NMDZ1_HUMAN NMDZ1_HUMAN]] Defects in GRIN1 are the cause of mental retardation autosomal dominant type 8 (MRD8) [MIM:[http://omim.org/entry/614254 614254]]. Mental retardation is characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period.<ref>PMID:21376300</ref>	+	[https://www.uniprot.org/uniprot/NMDE1_HUMAN NMDE1_HUMAN] Landau-Kleffner syndrome;Early-onset epileptic encephalopathy and intellectual disability due to GRIN2A mutation;Continuous spikes and waves during sleep;Rolandic epilepsy;Rolandic epilepsy - speech dyspraxia. The disease is caused by mutations affecting the gene represented in this entry. A chromosomal aberration involving GRIN2A has been found in a family with epilepsy and neurodevelopmental defects. Translocation t(16;17)(p13.2;q11.2). GRIN2A somatic mutations have been frequently found in cutaneous malignant melanoma, suggesting that the glutamate signaling pathway may play a role in the pathogenesis of melanoma.<ref>PMID:21499247</ref> <ref>PMID:24455489</ref>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/NMDE1_HUMAN NMDE1_HUMAN]] NMDA receptor subtype of glutamate-gated ion channels possesses high calcium permeability and voltage-dependent sensitivity to magnesium. Activation requires binding of agonist to both types of subunits. [[http://www.uniprot.org/uniprot/NMDZ1_HUMAN NMDZ1_HUMAN]] NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. This protein plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. It mediates neuronal functions in glutamate neurotransmission. Is involved in the cell surface targeting of NMDA receptors (By similarity).	+	[https://www.uniprot.org/uniprot/NMDE1_HUMAN NMDE1_HUMAN] NMDA receptor subtype of glutamate-gated ion channels possesses high calcium permeability and voltage-dependent sensitivity to magnesium. Activation requires binding of agonist to both types of subunits.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 29:		Line 28:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Lupardus~~, P J~~]]	+	[[Category: Lupardus PJ]]
-	[[Category: Wallweber~~, H J.A]]~~	+	[[Category: Wallweber HJA]]
-	~~[[Category: Channel]]~~	+
-	~~[[Category: Glutamate]]~~	+
-	~~[[Category: Nmda]]~~	+
-	~~[[Category: Receptor]]~~	+
-	~~[[Category: Transport protein~~]]	+

OCA at 08:43, 27 May 2020

2020-05-27T08:43:10Z

←Older revision		Revision as of 08:43, 27 May 2020
Line 1:		Line 1:

	==Structure of the human GluN1/GluN2A LBD in complex with N-ethyl-7-{[2-fluoro-3-(trifluoromethyl)phenyl]methyl}-2-methyl-5-oxo-5H-[1,3]thiazolo[3,2-a]pyrimidine-3-carboxamide (compound 29)==		==Structure of the human GluN1/GluN2A LBD in complex with N-ethyl-7-{[2-fluoro-3-(trifluoromethyl)phenyl]methyl}-2-methyl-5-oxo-5H-[1,3]thiazolo[3,2-a]pyrimidine-3-carboxamide (compound 29)==
-	<StructureSection load='5i2n' size='340' side='right' caption='[[5i2n]], [[Resolution\|resolution]] 2.12Å' scene=''>	+	<StructureSection load='5i2n' size='340' side='right'caption='[[5i2n]], [[Resolution\|resolution]] 2.12Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5i2n]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I2N OCA]. For a <b>guided tour on the structure components</b> use [http://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5I2N FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5i2n]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I2N OCA]. For a <b>guided tour on the structure components</b> use [http://proteopedia.org/fgij/fg.htm?mol=5I2N FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=67J:N-ETHYL-7-{[2-FLUORO-3-(TRIFLUOROMETHYL)PHENYL]METHYL}-2-METHYL-5-OXO-5H-[1,3]THIAZOLO[3,2-A]PYRIMIDINE-3-CARBOXAMIDE'>67J</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=GLY:GLYCINE'>GLY</scene></td></tr>	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=67J:N-ETHYL-7-{[2-FLUORO-3-(TRIFLUOROMETHYL)PHENYL]METHYL}-2-METHYL-5-OXO-5H-[1,3]THIAZOLO[3,2-A]PYRIMIDINE-3-CARBOXAMIDE'>67J</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=GLY:GLYCINE'>GLY</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5i2j\|5i2j]], [[5i2k\|5i2k]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5i2j\|5i2j]], [[5i2k\|5i2k]]</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=5i2n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i2n OCA], [http://pdbe.org/5i2n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i2n RCSB], [http://www.ebi.ac.uk/pdbsum/5i2n PDBsum]</span></td></tr>	+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GRIN2A, NMDAR2A ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), GRIN1, NMDAR1 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr>
		+	<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=5i2n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i2n OCA], [http://pdbe.org/5i2n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i2n RCSB], [http://www.ebi.ac.uk/pdbsum/5i2n PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5i2n ProSAT]</span></td></tr>
	</table>		</table>
	== Disease ==		== Disease ==
Line 21:		Line 22:
	</div>		</div>
	<div class="pdbe-citations 5i2n" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5i2n" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Glutamate receptor 3D structures\|Glutamate receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
		+	[[Category: Large Structures]]
	[[Category: Lupardus, P J]]		[[Category: Lupardus, P J]]
	[[Category: Wallweber, H J.A]]		[[Category: Wallweber, H J.A]]

OCA at 17:14, 10 May 2016

2016-05-10T17:14:04Z

←Older revision		Revision as of 17:14, 10 May 2016
Line 1:		Line 1:
-	'''Unreleased structure'''

-	The entry ~~5i2n~~ is ~~ON HOLD~~	+	==Structure of the human GluN1/GluN2A LBD in complex with N-ethyl-7-{[2-fluoro-3-(trifluoromethyl)phenyl]methyl}-2-methyl-5-oxo-5H-[1,3]thiazolo[3,2-a]pyrimidine-3-carboxamide (compound 29)==
		+	<StructureSection load='5i2n' size='340' side='right' caption='[[5i2n]], [[Resolution\|resolution]] 2.12Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5i2n]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5I2N OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5I2N FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=67J:N-ETHYL-7-{[2-FLUORO-3-(TRIFLUOROMETHYL)PHENYL]METHYL}-2-METHYL-5-OXO-5H-[1,3]THIAZOLO[3,2-A]PYRIMIDINE-3-CARBOXAMIDE'>67J</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=EPE:4-(2-HYDROXYETHYL)-1-PIPERAZINE+ETHANESULFONIC+ACID'>EPE</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=GLY:GLYCINE'>GLY</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5i2j\|5i2j]], [[5i2k\|5i2k]]</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=5i2n FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5i2n OCA], [http://pdbe.org/5i2n PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5i2n RCSB], [http://www.ebi.ac.uk/pdbsum/5i2n PDBsum]</span></td></tr>
		+	</table>
		+	== Disease ==
		+	[[http://www.uniprot.org/uniprot/NMDE1_HUMAN NMDE1_HUMAN]] Landau-Kleffner syndrome;Early-onset epileptic encephalopathy and intellectual disability due to GRIN2A mutation;Continuous spikes and waves during sleep;Rolandic epilepsy;Rolandic epilepsy - speech dyspraxia. The disease is caused by mutations affecting the gene represented in this entry. A chromosomal aberration involving GRIN2A has been found in a family with epilepsy and neurodevelopmental defects. Translocation t(16;17)(p13.2;q11.2). GRIN2A somatic mutations have been frequently found in cutaneous malignant melanoma, suggesting that the glutamate signaling pathway may play a role in the pathogenesis of melanoma.<ref>PMID:21499247</ref> <ref>PMID:24455489</ref> [[http://www.uniprot.org/uniprot/NMDZ1_HUMAN NMDZ1_HUMAN]] Defects in GRIN1 are the cause of mental retardation autosomal dominant type 8 (MRD8) [MIM:[http://omim.org/entry/614254 614254]]. Mental retardation is characterized by significantly below average general intellectual functioning associated with impairments in adaptative behavior and manifested during the developmental period.<ref>PMID:21376300</ref>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/NMDE1_HUMAN NMDE1_HUMAN]] NMDA receptor subtype of glutamate-gated ion channels possesses high calcium permeability and voltage-dependent sensitivity to magnesium. Activation requires binding of agonist to both types of subunits. [[http://www.uniprot.org/uniprot/NMDZ1_HUMAN NMDZ1_HUMAN]] NMDA receptor subtype of glutamate-gated ion channels with high calcium permeability and voltage-dependent sensitivity to magnesium. Mediated by glycine. This protein plays a key role in synaptic plasticity, synaptogenesis, excitotoxicity, memory acquisition and learning. It mediates neuronal functions in glutamate neurotransmission. Is involved in the cell surface targeting of NMDA receptors (By similarity).
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	The N-methyl-d-aspartate receptor (NMDAR) is a Na(+) and Ca(2+) permeable ionotropic glutamate receptor that is activated by the coagonists glycine and glutamate. NMDARs are critical to synaptic signaling and plasticity, and their dysfunction has been implicated in a number of neurological disorders, including schizophrenia, depression, and Alzheimer's disease. Herein we describe the discovery of potent GluN2A-selective NMDAR positive allosteric modulators (PAMs) starting from a high-throughput screening hit. Using structure-based design, we sought to increase potency at the GluN2A subtype, while improving selectivity against related alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). The structure-activity relationship of channel deactivation kinetics was studied using a combination of electrophysiology and protein crystallography. Effective incorporation of these strategies resulted in the discovery of GNE-0723 (46), a highly potent and brain penetrant GluN2A-selective NMDAR PAM suitable for in vivo characterization.

-	~~Authors~~: ~~Wallweber, H.J~~.A., Lupardus, P.J.	+	Discovery of GluN2A-Selective NMDA Receptor Positive Allosteric Modulators (PAMs): Tuning Deactivation Kinetics via Structure-Based Design.,Volgraf M, Sellers BD, Jiang Y, Wu G, Ly CQ, Villemure E, Pastor RM, Yuen PW, Lu A, Luo X, Liu M, Zhang S, Sun L, Fu Y, Lupardus PJ, Wallweber HJ, Liederer BM, Deshmukh G, Plise E, Tay S, Reynen P, Herrington J, Gustafson A, Liu Y, Dirksen A, Dietz MG, Liu Y, Wang TM, Hanson JE, Hackos D, Scearce-Levie K, Schwarz JB J Med Chem. 2016 Mar 24;59(6):2760-79. doi: 10.1021/acs.jmedchem.5b02010. Epub, 2016 Mar 8. PMID:26919761<ref>PMID:26919761</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Wallweber, H.J.A]]	+	<div class="pdbe-citations 5i2n" style="background-color:#fffaf0;"></div>
-	[[Category: ~~Lupardus, P.J~~]]	+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Lupardus, P J]]
		+	[[Category: Wallweber, H J.A]]
		+	[[Category: Channel]]
		+	[[Category: Glutamate]]
		+	[[Category: Nmda]]
		+	[[Category: Receptor]]
		+	[[Category: Transport protein]]

OCA: Protected "5i2n" [edit=sysop:move=sysop]

2016-02-21T01:29:34Z

Protected "5i2n" [edit=sysop:move=sysop]

←Older revision

Revision as of 01:29, 21 February 2016

OCA: New page: '''Unreleased structure''' The entry 5i2n is ON HOLD Authors: Wallweber, H.J.A., Lupardus, P.J. Description: Category: Unreleased Structures Category: Wallweber, H.J.A [[Categ...

2016-02-21T01:29:32Z

New page: '''Unreleased structure''' The entry 5i2n is ON HOLD Authors: Wallweber, H.J.A., Lupardus, P.J. Description: Category: Unreleased Structures Category: Wallweber, H.J.A [[Categ...

New page

'''Unreleased structure'''

The entry 5i2n is ON HOLD

Authors: Wallweber, H.J.A., Lupardus, P.J.

Description:
[[Category: Unreleased Structures]]
[[Category: Wallweber, H.J.A]]
[[Category: Lupardus, P.J]]