5ybg - Revision history

OCA at 08:25, 22 November 2023

OCA — Wed, 22 Nov 2023 08:25:55 GMT

←Older revision		Revision as of 08:25, 22 November 2023
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	==Crystal structure of the GluA2o LBD in complex with glutamate and LY451395==		==Crystal structure of the GluA2o LBD in complex with glutamate and LY451395==
-	<StructureSection load='5ybg' size='340' side='right' caption='[[5ybg]], [[Resolution\|resolution]] 1.52Å' scene=''>	+	<StructureSection load='5ybg' size='340' side='right'caption='[[5ybg]], [[Resolution\|resolution]] 1.52Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5ybg]] is a 6 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=5YBG OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5YBG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5ybg]] is a 6 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=5YBG OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5YBG FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8SO:N-[(2R)-2-[4-[4-[2-(methylsulfonylamino)ethyl]phenyl]phenyl]propyl]propane-2-sulfonamide'>8SO</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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]] 1.52Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GRIA2, GLUR2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=8SO:N-[(2R)-2-[4-[4-[2-(methylsulfonylamino)ethyl]phenyl]phenyl]propyl]propane-2-sulfonamide'>8SO</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5ybg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ybg OCA], [~~http~~://pdbe.org/5ybg PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5ybg RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5ybg PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5ybg 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=5ybg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ybg OCA], [https://pdbe.org/5ybg PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5ybg RCSB], [https://www.ebi.ac.uk/pdbsum/5ybg PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5ybg ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/GRIA2_HUMAN GRIA2_HUMAN]] Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.<ref>PMID:20614889</ref>	+	[https://www.uniprot.org/uniprot/GRIA2_HUMAN GRIA2_HUMAN] Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.<ref>PMID:20614889</ref>
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 19:		Line 19:
	</div>		</div>
	<div class="pdbe-citations 5ybg" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5ybg" 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: Homo sapiens]]
-	[[Category: Hirokawa, A]]	+	[[Category: Large Structures]]
-	[[Category: Igaki, S]]	+	[[Category: Hirokawa A]]
-	[[Category: Lane, W]]	+	[[Category: Igaki S]]
-	[[Category: Snell, G]]	+	[[Category: Lane W]]
-	[[Category: Sogabe, S]]	+	[[Category: Snell G]]
-	[[Category: Zama, Y]]	+	[[Category: Sogabe S]]
-	~~[[Category: Allosteric modulation complex]]~~	+	[[Category: Zama Y]]
-	~~[[Category: Ampa receptor ligand-binding domain]]~~	+
-	~~[[Category: Membrane protein]]~~	+
-	~~[[Category: Transport protein~~]]	+

OCA at 08:24, 22 February 2018

OCA — Thu, 22 Feb 2018 08:24:27 GMT

←Older revision		Revision as of 08:24, 22 February 2018
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	<StructureSection load='5ybg' size='340' side='right' caption='[[5ybg]], [[Resolution\|resolution]] 1.52Å' scene=''>		<StructureSection load='5ybg' size='340' side='right' caption='[[5ybg]], [[Resolution\|resolution]] 1.52Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5ybg]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YBG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YBG FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5ybg]] is a 6 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=5YBG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YBG FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8SO:N-[(2R)-2-[4-[4-[2-(methylsulfonylamino)ethyl]phenyl]phenyl]propyl]propane-2-sulfonamide'>8SO</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8SO:N-[(2R)-2-[4-[4-[2-(methylsulfonylamino)ethyl]phenyl]phenyl]propyl]propane-2-sulfonamide'>8SO</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</scene></td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GRIA2, GLUR2 ([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://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5ybg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ybg OCA], [http://pdbe.org/5ybg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ybg RCSB], [http://www.ebi.ac.uk/pdbsum/5ybg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ybg ProSAT]</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=5ybg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ybg OCA], [http://pdbe.org/5ybg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ybg RCSB], [http://www.ebi.ac.uk/pdbsum/5ybg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ybg ProSAT]</span></td></tr>
	</table>		</table>
Line 22:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Hirokawa, A]]		[[Category: Hirokawa, A]]
	[[Category: Igaki, S]]		[[Category: Igaki, S]]

OCA at 06:58, 17 January 2018

OCA — Wed, 17 Jan 2018 06:58:35 GMT

←Older revision		Revision as of 06:58, 17 January 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5ybg is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of the GluA2o LBD in complex with glutamate and LY451395==
		+	<StructureSection load='5ybg' size='340' side='right' caption='[[5ybg]], [[Resolution\|resolution]] 1.52Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5ybg]] is a 6 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5YBG OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5YBG FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8SO:N-[(2R)-2-[4-[4-[2-(methylsulfonylamino)ethyl]phenyl]phenyl]propyl]propane-2-sulfonamide'>8SO</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=ZN:ZINC+ION'>ZN</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=5ybg FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5ybg OCA], [http://pdbe.org/5ybg PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5ybg RCSB], [http://www.ebi.ac.uk/pdbsum/5ybg PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5ybg ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/GRIA2_HUMAN GRIA2_HUMAN]] Receptor for glutamate that functions as ligand-gated ion channel in the central nervous system and plays an important role in excitatory synaptic transmission. L-glutamate acts as an excitatory neurotransmitter at many synapses in the central nervous system. Binding of the excitatory neurotransmitter L-glutamate induces a conformation change, leading to the opening of the cation channel, and thereby converts the chemical signal to an electrical impulse. The receptor then desensitizes rapidly and enters a transient inactive state, characterized by the presence of bound agonist. In the presence of CACNG4 or CACNG7 or CACNG8, shows resensitization which is characterized by a delayed accumulation of current flux upon continued application of glutamate.<ref>PMID:20614889</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor (AMPA-R) potentiators with brain-derived neurotrophic factor (BDNF)-induction potential could be promising as therapeutic drugs for neuropsychiatric and neurological disorders. However, AMPA-R potentiators such as LY451646 have risks of narrow bell-shaped responses in pharmacological effects, including in vivo BDNF induction. Interestingly, LY451646 and LY451395, other AMPA-R potentiators, showed agonistic effects and exhibited bell-shaped responses in the BDNF production in primary neurons. We hypothesized that the agonistic property is related to the bell-shaped response and endeavored to discover novel AMPA-R potentiators with lower agonistic effects. LY451395 showed an agonistic effect in primary neurons, but not in a cell line expressing AMPA-Rs, in Ca2+ influx assays; thus, we used a Ca2+ influx assay in primary neurons and, from a chemical library, discovered two AMPA-R potentiators with lower agonistic effects: 2-(((5-methyl-3-(trifluoromethyl)-1H-pyrazol-1-yl)acetyl)amino)-4,5,6,7-tetrahydr o-1-benzothiophene-3-carboxamide (HBT1) and (3S)-1-(4-tert-butylphenyl)-N-((1R)-2-(dimethylamino)-1-phenylethyl)-3-isobutyl-2 -oxopyrrolidine-3-carboxamide (OXP1). In a patch-clamp study using primary neurons, HBT1 showed little agonistic effect, while both LY451395 and OXP1 showed remarkable agonistic effects. HBT1, but not OXP1, did not show remarkable bell-shaped response in BDNF production in primary neurons. HBT1 bound to the ligand-binding domain (LBD) of AMPA-R in a glutamate-dependent manner. The mode of HBT1 and LY451395 binding to a pocket in the LBD of AMPA-R differed: HBT1, but not LY451395, formed hydrogen bonds with S518 in the LBD. OXP1 may bind to a cryptic binding pocket on AMPA-R. Lower agonistic profile of HBT1 may associate with its lower risks of bell-shaped responses in BDNF production in primary neurons.

-	~~Authors: Sogabe~~, S., ~~Igaki, S~~., ~~Hirokawa,~~ A~~., Zama~~, Y., ~~Lane~~, W., ~~Snell, G~~.	+	HBT1, a novel AMPA receptor potentiator with lower agonistic effect, avoided bell-shaped response in in vitro BDNF production.,Kunugi A, Tajima Y, Kuno H, Sogabe S, Kimura H J Pharmacol Exp Ther. 2018 Jan 3. pii: jpet.117.245050. doi:, 10.1124/jpet.117.245050. PMID:29298820<ref>PMID:29298820</ref>

-	~~Description: Crystal structure~~ of the ~~GluA2o LBD in complex with glutamate and LY451395~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: ~~Snell~~, G]]	+	<div class="pdbe-citations 5ybg" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Hirokawa, A]]
		+	[[Category: Igaki, S]]
	[[Category: Lane, W]]		[[Category: Lane, W]]
		+	[[Category: Snell, G]]
	[[Category: Sogabe, S]]		[[Category: Sogabe, S]]
-	[[Category: Hirokawa, A]]
	[[Category: Zama, Y]]		[[Category: Zama, Y]]
-	[[Category: ~~Igaki, S~~]]	+	[[Category: Allosteric modulation complex]]
		+	[[Category: Ampa receptor ligand-binding domain]]
		+	[[Category: Membrane protein]]
		+	[[Category: Transport protein]]

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

OCA — Wed, 27 Sep 2017 16:22:25 GMT

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

←Older revision

Revision as of 16:22, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5ybg is ON HOLD until Paper Publication Authors: Sogabe, S., Igaki, S., Hirokawa, A., Zama, Y., Lane, W., Snell, G. Description: Crystal structure ...

OCA — Wed, 27 Sep 2017 16:22:24 GMT

New page: '''Unreleased structure''' The entry 5ybg is ON HOLD until Paper Publication Authors: Sogabe, S., Igaki, S., Hirokawa, A., Zama, Y., Lane, W., Snell, G. Description: Crystal structure ...

New page

'''Unreleased structure'''

The entry 5ybg is ON HOLD until Paper Publication

Authors: Sogabe, S., Igaki, S., Hirokawa, A., Zama, Y., Lane, W., Snell, G.

Description: Crystal structure of the GluA2o LBD in complex with glutamate and LY451395
[[Category: Unreleased Structures]]
[[Category: Snell, G]]
[[Category: Lane, W]]
[[Category: Sogabe, S]]
[[Category: Hirokawa, A]]
[[Category: Zama, Y]]
[[Category: Igaki, S]]