5o9a - Revision history

OCA at 09:37, 6 December 2023

OCA — Wed, 06 Dec 2023 09:37:33 GMT

←Older revision		Revision as of 09:37, 6 December 2023
Line 1:		Line 1:

	==Crystal structure of the GluA2 ligand-binding domain (S1S2J-L504Y-N775S) in complex with glutamate and BPAM121 at 1.78 A resolution==		==Crystal structure of the GluA2 ligand-binding domain (S1S2J-L504Y-N775S) in complex with glutamate and BPAM121 at 1.78 A resolution==
-	<StructureSection load='5o9a' size='340' side='right' caption='[[5o9a]], [[Resolution\|resolution]] 1.78Å' scene=''>	+	<StructureSection load='5o9a' size='340' side='right'caption='[[5o9a]], [[Resolution\|resolution]] 1.78Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5o9a]] is a 4 chain structure with sequence from [~~http~~://en.wikipedia.org/wiki/~~Buffalo_rat Buffalo rat~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O9A OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5O9A FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5o9a]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O9A OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5O9A FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7M6:7-CHLORO-4-(2-FLUOROETHYL)-2,3-DIHYDRO-1,2,4-BENZOTHIADIAZINE+1,1-DIOXIDE'>7M6</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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]] 1.78Å</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=10116 Buffalo rat])~~</td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7M6:7-CHLORO-4-(2-FLUOROETHYL)-2,3-DIHYDRO-1,2,4-BENZOTHIADIAZINE+1,1-DIOXIDE'>7M6</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5o9a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o9a OCA], [~~http~~://pdbe.org/5o9a PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5o9a RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5o9a PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5o9a 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=5o9a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o9a OCA], [https://pdbe.org/5o9a PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5o9a RCSB], [https://www.ebi.ac.uk/pdbsum/5o9a PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5o9a ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/GRIA2_RAT GRIA2_RAT]] 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:9351977</ref> <ref>PMID:19265014</ref> <ref>PMID:21172611</ref> <ref>PMID:12501192</ref> <ref>PMID:12015593</ref> <ref>PMID:12872125</ref> <ref>PMID:12730367</ref> <ref>PMID:16192394</ref> <ref>PMID:15591246</ref> <ref>PMID:17018279</ref> <ref>PMID:16483599</ref> <ref>PMID:19946266</ref> <ref>PMID:21317873</ref> <ref>PMID:21846932</ref>	+	[https://www.uniprot.org/uniprot/GRIA2_RAT GRIA2_RAT] 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:9351977</ref> <ref>PMID:19265014</ref> <ref>PMID:21172611</ref> <ref>PMID:12501192</ref> <ref>PMID:12015593</ref> <ref>PMID:12872125</ref> <ref>PMID:12730367</ref> <ref>PMID:16192394</ref> <ref>PMID:15591246</ref> <ref>PMID:17018279</ref> <ref>PMID:16483599</ref> <ref>PMID:19946266</ref> <ref>PMID:21317873</ref> <ref>PMID:21846932</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 5o9a" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5o9a" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Glutamate receptor 3D structures\|Glutamate receptor 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Buffalo rat~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Frydenvang, K A~~]]	+	[[Category: Rattus norvegicus]]
-	[[Category: ~~Kastrup, J S~~]]	+	[[Category: Frydenvang KA]]
-	[[Category: ~~Laulumaa, S~~]]	+	[[Category: Kastrup JS]]
-	[[Category: ~~Rovinskaja, K~~]]	+	[[Category: Laulumaa S]]
-	[[Category: ~~Ampa receptor]]~~	+	[[Category: Rovinskaja K]]
-	~~[[Category: Glua2]]~~	+
-	~~[[Category: Glur2]]~~	+
-	~~[[Category: Ionotropic glutamate receptor]]~~	+
-	~~[[Category: L504y-n775]]~~	+
-	~~[[Category: Ligand-binding domain]]~~	+
-	~~[[Category: Membrane protein]]~~	+
-	~~[[Category: Positive allosteric modulator]]~~	+
-	~~[[Category: Signaling protein~~]]	+

OCA at 20:44, 24 January 2018

OCA — Wed, 24 Jan 2018 20:44:59 GMT

←Older revision		Revision as of 20:44, 24 January 2018
Line 3:		Line 3:
	<StructureSection load='5o9a' size='340' side='right' caption='[[5o9a]], [[Resolution\|resolution]] 1.78Å' scene=''>		<StructureSection load='5o9a' size='340' side='right' caption='[[5o9a]], [[Resolution\|resolution]] 1.78Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5o9a]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O9A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O9A FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5o9a]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O9A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O9A FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7M6:7-CHLORO-4-(2-FLUOROETHYL)-2,3-DIHYDRO-1,2,4-BENZOTHIADIAZINE+1,1-DIOXIDE'>7M6</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7M6:7-CHLORO-4-(2-FLUOROETHYL)-2,3-DIHYDRO-1,2,4-BENZOTHIADIAZINE+1,1-DIOXIDE'>7M6</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=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=5o9a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o9a OCA], [http://pdbe.org/5o9a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5o9a RCSB], [http://www.ebi.ac.uk/pdbsum/5o9a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5o9a 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=5o9a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o9a OCA], [http://pdbe.org/5o9a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5o9a RCSB], [http://www.ebi.ac.uk/pdbsum/5o9a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5o9a ProSAT]</span></td></tr>
	</table>		</table>
Line 22:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Buffalo rat]]
	[[Category: Frydenvang, K A]]		[[Category: Frydenvang, K A]]
	[[Category: Kastrup, J S]]		[[Category: Kastrup, J S]]

OCA at 05:45, 3 January 2018

OCA — Wed, 03 Jan 2018 05:45:11 GMT

←Older revision		Revision as of 05:45, 3 January 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5o9a is ~~ON HOLD~~	+	==Crystal structure of the GluA2 ligand-binding domain (S1S2J-L504Y-N775S) in complex with glutamate and BPAM121 at 1.78 A resolution==
		+	<StructureSection load='5o9a' size='340' side='right' caption='[[5o9a]], [[Resolution\|resolution]] 1.78Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5o9a]] is a 4 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5O9A OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5O9A FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=7M6:7-CHLORO-4-(2-FLUOROETHYL)-2,3-DIHYDRO-1,2,4-BENZOTHIADIAZINE+1,1-DIOXIDE'>7M6</scene>, <scene name='pdbligand=CIT:CITRIC+ACID'>CIT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=EDO:1,2-ETHANEDIOL'>EDO</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=PEG:DI(HYDROXYETHYL)ETHER'>PEG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</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=5o9a FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5o9a OCA], [http://pdbe.org/5o9a PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5o9a RCSB], [http://www.ebi.ac.uk/pdbsum/5o9a PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5o9a ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/GRIA2_RAT GRIA2_RAT]] 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:9351977</ref> <ref>PMID:19265014</ref> <ref>PMID:21172611</ref> <ref>PMID:12501192</ref> <ref>PMID:12015593</ref> <ref>PMID:12872125</ref> <ref>PMID:12730367</ref> <ref>PMID:16192394</ref> <ref>PMID:15591246</ref> <ref>PMID:17018279</ref> <ref>PMID:16483599</ref> <ref>PMID:19946266</ref> <ref>PMID:21317873</ref> <ref>PMID:21846932</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	We report here the synthesis of 7-phenoxy-substituted 3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxides and their evaluation as AMPA receptor positive allosteric modulators (AMPApams). The impact of substitution on the phenoxy ring and on the nitrogen atom at the 4-position was examined. At GluA2(Q) expressed in HEK293 cells (calcium flux experiment), the most potent compound was 11m (4-cyclopropyl-7-(3-methoxyphenoxy)-3,4-dihydro-2H-1,2,4-benzothiadiazine 1,1-dioxide, EC50 = 2.0 nM). The Hill coefficient in the screening and the shape of the dimerization curve in small-angle X-ray scattering (SAXS) experiments using isolated GluA2 ligand-binding domain (GluA2-LBD) are consistent with binding of one molecule of 11m per dimer interface, contrary to most benzothiadiazine dioxides developed to date. This observation was confirmed by the X-ray structure of 11m bound to GluA2-LBD and by NMR. This is the first benzothiadiazine dioxide AMPApam to reach the nanomolar range.

-	~~Authors~~:	+	7-Phenoxy-Substituted 3,4-Dihydro-2H-1,2,4-benzothiadiazine 1,1-Dioxides as Positive Allosteric Modulators of alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors with Nanomolar Potency.,Goffin E, Drapier T, Larsen AP, Geubelle P, Ptak CP, Laulumaa S, Rovinskaja K, Gilissen J, Tullio P, Olsen L, Frydenvang K, Pirotte B, Hanson J, Oswald RE, Kastrup JS, Francotte P J Med Chem. 2017 Dec 19. doi: 10.1021/acs.jmedchem.7b01323. PMID:29256599<ref>PMID:29256599</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5o9a" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Frydenvang, K A]]
		+	[[Category: Kastrup, J S]]
		+	[[Category: Laulumaa, S]]
		+	[[Category: Rovinskaja, K]]
		+	[[Category: Ampa receptor]]
		+	[[Category: Glua2]]
		+	[[Category: Glur2]]
		+	[[Category: Ionotropic glutamate receptor]]
		+	[[Category: L504y-n775]]
		+	[[Category: Ligand-binding domain]]
		+	[[Category: Membrane protein]]
		+	[[Category: Positive allosteric modulator]]
		+	[[Category: Signaling protein]]

OCA: Protected "5o9a" [edit=sysop:move=sysop]

OCA — Wed, 27 Sep 2017 12:10:52 GMT

Protected "5o9a" [edit=sysop:move=sysop]

←Older revision

Revision as of 12:10, 27 September 2017

OCA: New page: '''Unreleased structure''' The entry 5o9a is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 27 Sep 2017 12:10:51 GMT

New page: '''Unreleased structure''' The entry 5o9a is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 5o9a is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]