5nih - Revision history

OCA at 12:59, 15 November 2023

2023-11-15T12:59:46Z

←Older revision		Revision as of 12:59, 15 November 2023
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	==Crystal structure of the GluA2 ligand-binding domain (S1S2J) in complex with agonist LM-12b at 1.3 A resolution.==		==Crystal structure of the GluA2 ligand-binding domain (S1S2J) in complex with agonist LM-12b at 1.3 A resolution.==
-	<StructureSection load='5nih' size='340' side='right' caption='[[5nih]], [[Resolution\|resolution]] 1.30Å' scene=''>	+	<StructureSection load='5nih' size='340' side='right'caption='[[5nih]], [[Resolution\|resolution]] 1.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5nih]] is a 2 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=5NIH OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5NIH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5nih]] is a 2 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=5NIH OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5NIH FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8VE:(3~{a}~{R},4~{S},6~{a}~{R})-1-methyl-4,5,6,6~{a}-tetrahydro-3~{a}~{H}-pyrrolo[3,4-c]pyrazole-3,4-dicarboxylic+acid'>8VE</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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]] 1.3Å</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=8VE:(3~{a}~{R},4~{S},6~{a}~{R})-1-methyl-4,5,6,6~{a}-tetrahydro-3~{a}~{H}-pyrrolo[3,4-c]pyrazole-3,4-dicarboxylic+acid'>8VE</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=5nih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nih OCA], [~~http~~://pdbe.org/5nih PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5nih RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5nih PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5nih 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=5nih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nih OCA], [https://pdbe.org/5nih PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5nih RCSB], [https://www.ebi.ac.uk/pdbsum/5nih PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5nih 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 5nih" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5nih" 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: ~~Agonist]]~~	+	[[Category: Laulumaa S]]
-	~~[[Category: Ampa receptor]]~~	+
-	~~[[Category: Glua2]]~~	+
-	~~[[Category: Glur2]]~~	+
-	~~[[Category: Ionotropic glutamate receptor]]~~	+
-	~~[[Category: Ligand-binding domain]]~~	+
-	~~[[Category: Membrane protein~~]]	+

OCA at 06:10, 8 March 2018

2018-03-08T06:10:28Z

←Older revision		Revision as of 06:10, 8 March 2018
Line 3:		Line 3:
	<StructureSection load='5nih' size='340' side='right' caption='[[5nih]], [[Resolution\|resolution]] 1.30Å' scene=''>		<StructureSection load='5nih' size='340' side='right' caption='[[5nih]], [[Resolution\|resolution]] 1.30Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5nih]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NIH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NIH FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5nih]] is a 2 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=5NIH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NIH FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8VE:(3~{a}~{R},4~{S},6~{a}~{R})-1-methyl-4,5,6,6~{a}-tetrahydro-3~{a}~{H}-pyrrolo[3,4-c]pyrazole-3,4-dicarboxylic+acid'>8VE</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=8VE:(3~{a}~{R},4~{S},6~{a}~{R})-1-methyl-4,5,6,6~{a}-tetrahydro-3~{a}~{H}-pyrrolo[3,4-c]pyrazole-3,4-dicarboxylic+acid'>8VE</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=5nih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nih OCA], [http://pdbe.org/5nih PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nih RCSB], [http://www.ebi.ac.uk/pdbsum/5nih PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nih 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=5nih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nih OCA], [http://pdbe.org/5nih PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nih RCSB], [http://www.ebi.ac.uk/pdbsum/5nih PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nih 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 10:10, 27 September 2017

2017-09-27T10:10:43Z

←Older revision		Revision as of 10:10, 27 September 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5nih is ~~ON HOLD~~	+	==Crystal structure of the GluA2 ligand-binding domain (S1S2J) in complex with agonist LM-12b at 1.3 A resolution.==
		+	<StructureSection load='5nih' size='340' side='right' caption='[[5nih]], [[Resolution\|resolution]] 1.30Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5nih]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5NIH OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5NIH FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=8VE:(3~{a}~{R},4~{S},6~{a}~{R})-1-methyl-4,5,6,6~{a}-tetrahydro-3~{a}~{H}-pyrrolo[3,4-c]pyrazole-3,4-dicarboxylic+acid'>8VE</scene>, <scene name='pdbligand=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</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=5nih FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5nih OCA], [http://pdbe.org/5nih PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5nih RCSB], [http://www.ebi.ac.uk/pdbsum/5nih PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5nih 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 ==
		+	Ionotropic glutamate receptors (iGluRs) are involved in most of the fast excitatory synaptic transmission in the central nervous system. These receptors are important for learning and memory formation, but are also involved in the development of diseases such as Alzheimer's disease, epilepsy and depression. To understand the function of different types of iGluRs, selective agonists are invaluable as pharmacological tool compounds. Here, we report binding affinities of two bicyclic, conformationally restricted analogues of glutamate (CIP-AS and LM-12b) at AMPA (GluA2 and GluA3) and kainate receptor subunits (GluK1-3 and GluK5). Both CIP-AS and LM-12b were found to be GluK3-preferring agonists, with Ki of 6 and 22 nM, respectively, at recombinant GluK3 receptors. The detailed binding mode of CIP-AS and LM-12b in the ligand-binding domains of the AMPA receptor subunit GluA2 (GluA2-LBD) and the kainate receptor subunits GluK1 (GluK1-LBD) and GluK3 (GluK3-LBD) was investigated by X-ray crystallography. CIP-AS stabilized all three receptor constructs in conformations similar to those with kainate. Remarkably, whereas LM-12b bound in a similar manner to CIP-AS in GluA2-LBD and GluK3-LBD, it introduced full closure of the ligand-binding domain in GluK1-LBD and formation of a D1-D2 interlobe hydrogen bond between Glu441 and Ser721, as also observed with glutamate. As the binding affinity of LM-12b at GluK1 is approximately 8-fold better than that for CIP-AS (Ki of 85 and 656 nM, respectively), it shows that small changes in agonist structure can lead to prominent differences in structure and function.

-	~~Authors: Laulumaa~~, S., ~~Frydenvang~~, K~~.A.~~, ~~Kastrup~~, J.S.	+	Structure and Affinity of Two Bicyclic Glutamate Analogues at AMPA and Kainate Receptors.,Mollerud S, Pinto A, Marconi L, Frydenvang K, Thorsen TS, Laulumaa S, Venskutonyte R, Winther S, Moral AMC, Tamborini L, Conti P, Pickering DS, Kastrup JS ACS Chem Neurosci. 2017 Sep 20;8(9):2056-2064. doi: 10.1021/acschemneuro.7b00201., Epub 2017 Jul 21. PMID:28691798<ref>PMID:28691798</ref>

-	~~Description: Crystal structure~~ of the ~~GluA2 ligand-binding domain (S1S2J) in complex with agonist LM1-2b at 1~~.~~3 A resolution~~.	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
-	[[Category: Kastrup, J.S]]	+	<div class="pdbe-citations 5nih" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Frydenvang, K A]]
		+	[[Category: Kastrup, J S]]
	[[Category: Laulumaa, S]]		[[Category: Laulumaa, S]]
-	[[Category: ~~Frydenvang, K.A~~]]	+	[[Category: Agonist]]
		+	[[Category: Ampa receptor]]
		+	[[Category: Glua2]]
		+	[[Category: Glur2]]
		+	[[Category: Ionotropic glutamate receptor]]
		+	[[Category: Ligand-binding domain]]
		+	[[Category: Membrane protein]]

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

2017-04-05T10:10:45Z

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

←Older revision

Revision as of 10:10, 5 April 2017

OCA: New page: '''Unreleased structure''' The entry 5nih is ON HOLD Authors: Laulumaa, S., Frydenvang, K.A., Kastrup, J.S. Description: Crystal structure of the GluA2 ligand-binding domain (S1S2J) in...

2017-04-05T10:10:43Z

New page: '''Unreleased structure''' The entry 5nih is ON HOLD Authors: Laulumaa, S., Frydenvang, K.A., Kastrup, J.S. Description: Crystal structure of the GluA2 ligand-binding domain (S1S2J) in...

New page

'''Unreleased structure'''

The entry 5nih is ON HOLD

Authors: Laulumaa, S., Frydenvang, K.A., Kastrup, J.S.

Description: Crystal structure of the GluA2 ligand-binding domain (S1S2J) in complex with agonist LM1-2b at 1.3 A resolution.
[[Category: Unreleased Structures]]
[[Category: Kastrup, J.S]]
[[Category: Laulumaa, S]]
[[Category: Frydenvang, K.A]]