3tkd - Revision history

OCA at 13:31, 14 March 2024

OCA — Thu, 14 Mar 2024 13:31:50 GMT

←Older revision		Revision as of 13:31, 14 March 2024
Line 3:		Line 3:
	<StructureSection load='3tkd' size='340' side='right'caption='[[3tkd]], [[Resolution\|resolution]] 1.45Å' scene=''>		<StructureSection load='3tkd' size='340' side='right'caption='[[3tkd]], [[Resolution\|resolution]] 1.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3tkd]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/~~Buffalo_rat Buffalo rat~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TKD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TKD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3tkd]] 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=3TKD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TKD FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CYZ:CYCLOTHIAZIDE'>CYZ</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</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]] 1.45Å</td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1lbc\|1lbc]], [[1lbb\|1lbb]], [[1lb9\|1lb9]], [[3h6t\|3h6t]], [[3il1\|3il1]]</div></td></tr>	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CYZ:CYCLOTHIAZIDE'>CYZ</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</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 ([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=3tkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tkd OCA], [https://pdbe.org/3tkd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tkd RCSB], [https://www.ebi.ac.uk/pdbsum/3tkd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tkd 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=3tkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tkd OCA], [https://pdbe.org/3tkd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tkd RCSB], [https://www.ebi.ac.uk/pdbsum/3tkd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tkd ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[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>	+	[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;">~~	+
-	~~== Publication Abstract from PubMed ==~~	+
-	Positive allosteric modulators of the ionotropic glutamate receptor-2 (GluA2) are promising compounds for the treatment of cognitive disorders, e.g. Alzheimer's disease. These modulators bind within the dimer interface of the ligand-binding domain and stabilize the agonist-bound conformation slowing receptor desensitization and/or deactivation. Here, we employ isothermal titration calorimetry to determine binding affinities and thermodynamic details of binding of modulators of GluA2. A mutant of the ligand-binding domain of GluA2 (LBD-L483Y-N754S) that forms a stable dimer in solution was utilized. The potent GluA2 modulator BPAM-97 was used as reference compound. Evidence that BPAM-97 binds in the same pocket as the well-known GluA2 modulator cyclothiazide was obtained from X-ray structures. The LBD-L483Y-N754S:BPAM-97 complex has Kd of 5.6 microM (H = -4.9 kcal/mol, -TS = -2.3 kcal/mol). BPAM-97 was used in a displacement assay to determine Kd of 0.46 mM (H = -1.2 kcal/mol, -TS = -3.3 kcal/mol) of the LBD-L483Y-N754S:IDRA-21 complex. The major structural factors increasing the potency of BPAM-97 over IDRA-21 are the increased vdW contacts to primarily Met-496 in GluA2 imposed by the ethyl substituent of BPAM-97. These results add important information on binding affinities and thermodynamic details, and provide a new tool in development of drugs against cognitive disorders.	+
-		+
-	Thermodynamics and structural analysis of positive allosteric modulation of the ionotropic glutamate receptor GluA2.,Krintel C, Frydenvang K, Olsen L, Kristensen MT, de Barrios O, Naur P, Francotte P, Pirotte B, Gajhede M, Kastrup JS Biochem J. 2011 Sep 7. PMID:21895609<ref>PMID:21895609</ref>	+
-		+
-	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~	+
-	~~</div>~~	+
-	~~<div class="pdbe-citations 3tkd" style="background-color:#fffaf0;"></div~~>	+

	==See Also==		==See Also==
Line 27:		Line 17:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: Buffalo rat]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Frydenvang, K]]	+	[[Category: Rattus norvegicus]]
-	[[Category: Gajhede, M]]	+	[[Category: Frydenvang K]]
-	[[Category: Kastrup~~, J S~~]]	+	[[Category: Gajhede M]]
-	[[Category: Krintel, C]]	+	[[Category: Kastrup JS]]
-	~~[[Category: Allosteric modulation]]~~	+	[[Category: Krintel C]]
-	~~[[Category: Ampa receptor ligand-binding domain]]~~	+
-	~~[[Category: Cyclothiazide]]~~	+
-	~~[[Category: Glua2 s1s2j-l483y-n754]]~~	+
-	~~[[Category: Membrane protein~~]]	+

OCA at 17:02, 6 July 2022

OCA — Wed, 06 Jul 2022 17:02:01 GMT

←Older revision		Revision as of 17:02, 6 July 2022
Line 1:		Line 1:

	==Crystal structure of the GluA2 ligand-binding domain (S1S2J-L483Y-N754S) in complex with glutamate and cyclothiazide at 1.45 A resolution==		==Crystal structure of the GluA2 ligand-binding domain (S1S2J-L483Y-N754S) in complex with glutamate and cyclothiazide at 1.45 A resolution==
-	<StructureSection load='3tkd' size='340' side='right' caption='[[3tkd]], [[Resolution\|resolution]] 1.45Å' scene=''>	+	<StructureSection load='3tkd' size='340' side='right'caption='[[3tkd]], [[Resolution\|resolution]] 1.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3tkd]] 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=3TKD OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=3TKD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3tkd]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Buffalo_rat Buffalo rat]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TKD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=3TKD FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CYZ:CYCLOTHIAZIDE'>CYZ</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</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" id="ligandDat"><scene name='pdbligand=CYZ:CYCLOTHIAZIDE'>CYZ</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1lbc\|1lbc]], [[1lbb\|1lbb]], [[1lb9\|1lb9]], [[3h6t\|3h6t]], [[3il1\|3il1]]</td></tr>	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat"><div style='overflow: auto; max-height: 3em;'>[[1lbc\|1lbc]], [[1lbb\|1lbb]], [[1lb9\|1lb9]], [[3h6t\|3h6t]], [[3il1\|3il1]]</div></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='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">GriA2, Glur2 ([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=3tkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tkd OCA], [~~http~~://pdbe.org/3tkd PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=3tkd RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/3tkd PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=3tkd 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=3tkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tkd OCA], [https://pdbe.org/3tkd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=3tkd RCSB], [https://www.ebi.ac.uk/pdbsum/3tkd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=3tkd 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 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 28:		Line 28:
	</StructureSection>		</StructureSection>
	[[Category: Buffalo rat]]		[[Category: Buffalo rat]]
		+	[[Category: Large Structures]]
	[[Category: Frydenvang, K]]		[[Category: Frydenvang, K]]
	[[Category: Gajhede, M]]		[[Category: Gajhede, M]]

OCA at 09:38, 4 August 2016

OCA — Thu, 04 Aug 2016 09:38:38 GMT

←Older revision		Revision as of 09:38, 4 August 2016
Line 1:		Line 1:
		+
	==Crystal structure of the GluA2 ligand-binding domain (S1S2J-L483Y-N754S) in complex with glutamate and cyclothiazide at 1.45 A resolution==		==Crystal structure of the GluA2 ligand-binding domain (S1S2J-L483Y-N754S) in complex with glutamate and cyclothiazide at 1.45 A resolution==
	<StructureSection load='3tkd' size='340' side='right' caption='[[3tkd]], [[Resolution\|resolution]] 1.45Å' scene=''>		<StructureSection load='3tkd' size='340' side='right' caption='[[3tkd]], [[Resolution\|resolution]] 1.45Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[3tkd]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/~~Rattus_norvegicus Rattus norvegicus~~]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TKD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TKD FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[3tkd]] 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=3TKD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TKD FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CYZ:CYCLOTHIAZIDE'>CYZ</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</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=CYZ:CYCLOTHIAZIDE'>CYZ</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1lbc\|1lbc]], [[1lbb\|1lbb]], [[1lb9\|1lb9]], [[3h6t\|3h6t]], [[3il1\|3il1]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1lbc\|1lbc]], [[1lbb\|1lbb]], [[1lb9\|1lb9]], [[3h6t\|3h6t]], [[3il1\|3il1]]</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 ~~Rattus norvegicus~~])</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=3tkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tkd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tkd RCSB], [http://www.ebi.ac.uk/pdbsum/3tkd 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=3tkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tkd OCA], [http://pdbe.org/3tkd PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=3tkd RCSB], [http://www.ebi.ac.uk/pdbsum/3tkd PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=3tkd 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 3tkd" style="background-color:#fffaf0;"></div>

	==See Also==		==See Also==
Line 25:		Line 27:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Rattus norvegicus~~]]	+	[[Category: Buffalo rat]]
	[[Category: Frydenvang, K]]		[[Category: Frydenvang, K]]
	[[Category: Gajhede, M]]		[[Category: Gajhede, M]]

OCA at 08:23, 24 December 2014

OCA — Wed, 24 Dec 2014 08:23:44 GMT

←Older revision		Revision as of 08:23, 24 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=3tkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tkd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tkd RCSB], [http://www.ebi.ac.uk/pdbsum/3tkd 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=3tkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tkd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tkd RCSB], [http://www.ebi.ac.uk/pdbsum/3tkd PDBsum]</span></td></tr>
	</table>		</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;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==

OCA at 17:52, 9 December 2014

OCA — Tue, 09 Dec 2014 17:52:25 GMT

←Older revision		Revision as of 17:52, 9 December 2014
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-	[[~~Image:~~3tkd.~~png~~\|~~left~~\|~~200px~~]]	+	==Crystal structure of the GluA2 ligand-binding domain (S1S2J-L483Y-N754S) in complex with glutamate and cyclothiazide at 1.45 A resolution==
		+	<StructureSection load='3tkd' size='340' side='right' caption='[[3tkd]], [[Resolution\|resolution]] 1.45Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[3tkd]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TKD OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=3TKD FirstGlance]. <br>
		+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CYZ:CYCLOTHIAZIDE'>CYZ</scene>, <scene name='pdbligand=GLU:GLUTAMIC+ACID'>GLU</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
		+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[1lbc\|1lbc]], [[1lbb\|1lbb]], [[1lb9\|1lb9]], [[3h6t\|3h6t]], [[3il1\|3il1]]</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 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=3tkd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=3tkd OCA], [http://www.rcsb.org/pdb/explore.do?structureId=3tkd RCSB], [http://www.ebi.ac.uk/pdbsum/3tkd PDBsum]</span></td></tr>
		+	</table>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Positive allosteric modulators of the ionotropic glutamate receptor-2 (GluA2) are promising compounds for the treatment of cognitive disorders, e.g. Alzheimer's disease. These modulators bind within the dimer interface of the ligand-binding domain and stabilize the agonist-bound conformation slowing receptor desensitization and/or deactivation. Here, we employ isothermal titration calorimetry to determine binding affinities and thermodynamic details of binding of modulators of GluA2. A mutant of the ligand-binding domain of GluA2 (LBD-L483Y-N754S) that forms a stable dimer in solution was utilized. The potent GluA2 modulator BPAM-97 was used as reference compound. Evidence that BPAM-97 binds in the same pocket as the well-known GluA2 modulator cyclothiazide was obtained from X-ray structures. The LBD-L483Y-N754S:BPAM-97 complex has Kd of 5.6 microM (H = -4.9 kcal/mol, -TS = -2.3 kcal/mol). BPAM-97 was used in a displacement assay to determine Kd of 0.46 mM (H = -1.2 kcal/mol, -TS = -3.3 kcal/mol) of the LBD-L483Y-N754S:IDRA-21 complex. The major structural factors increasing the potency of BPAM-97 over IDRA-21 are the increased vdW contacts to primarily Met-496 in GluA2 imposed by the ethyl substituent of BPAM-97. These results add important information on binding affinities and thermodynamic details, and provide a new tool in development of drugs against cognitive disorders.

-	~~{{STRUCTURE_3tkd\| PDB=3tkd \| SCENE= }}~~	+	Thermodynamics and structural analysis of positive allosteric modulation of the ionotropic glutamate receptor GluA2.,Krintel C, Frydenvang K, Olsen L, Kristensen MT, de Barrios O, Naur P, Francotte P, Pirotte B, Gajhede M, Kastrup JS Biochem J. 2011 Sep 7. PMID:21895609<ref>PMID:21895609</ref>

-	~~===Crystal structure~~ of the ~~GluA2 ligand-binding domain (S1S2J-L483Y-N754S) in complex with glutamate and cyclothiazide at 1~~.~~45 A resolution===~~	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-		+	</div>
-	~~{{ABSTRACT_PUBMED_21895609}}~~	+
-		+
-	~~==About this Structure==~~	+
-	~~[[3tkd]] is a 2 chain structure with sequence from [http://en~~.~~wikipedia~~.~~org~~/~~wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TKD OCA].~~	+

	==See Also==		==See Also==
	*[[Ionotropic Glutamate Receptors\|Ionotropic Glutamate Receptors]]		*[[Ionotropic Glutamate Receptors\|Ionotropic Glutamate Receptors]]
-		+	== References ==
-	==~~Reference~~==	+	<references/>
-	<~~ref group="xtra">PMID:021895609<~~/~~ref~~><~~ref group="xtra">PMID:012015593</ref><references group="xtra"~~/>	+	__TOC__
		+	</StructureSection>
	[[Category: Rattus norvegicus]]		[[Category: Rattus norvegicus]]
-	[[Category: Frydenvang, K.]]	+	[[Category: Frydenvang, K]]
-	[[Category: Gajhede, M.]]	+	[[Category: Gajhede, M]]
-	[[Category: Kastrup, J S.]]	+	[[Category: Kastrup, J S]]
-	[[Category: Krintel, C.]]	+	[[Category: Krintel, C]]
	[[Category: Allosteric modulation]]		[[Category: Allosteric modulation]]
	[[Category: Ampa receptor ligand-binding domain]]		[[Category: Ampa receptor ligand-binding domain]]

OCA at 05:46, 20 October 2012

OCA — Sat, 20 Oct 2012 05:46:21 GMT

←Older revision		Revision as of 05:46, 20 October 2012
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	==About this Structure==		==About this Structure==
-	[[3tkd]] is a 2 chain structure ~~of [[Ionotropic Glutamate Receptors]]~~ with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TKD OCA].	+	[[3tkd]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TKD OCA].

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

OCA at 11:04, 25 July 2012

OCA — Wed, 25 Jul 2012 11:04:14 GMT

←Older revision		Revision as of 11:04, 25 July 2012
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	[[Image:3tkd.png\|left\|200px]]		[[Image:3tkd.png\|left\|200px]]

-	<!--
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	{{STRUCTURE_3tkd\| PDB=3tkd \| SCENE= }}		{{STRUCTURE_3tkd\| PDB=3tkd \| SCENE= }}

	===Crystal structure of the GluA2 ligand-binding domain (S1S2J-L483Y-N754S) in complex with glutamate and cyclothiazide at 1.45 A resolution===		===Crystal structure of the GluA2 ligand-binding domain (S1S2J-L483Y-N754S) in complex with glutamate and cyclothiazide at 1.45 A resolution===

-
-	<!--
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-	(as it appears on PubMed at http://www.pubmed.gov), where 21895609 is the PubMed ID number.
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	{{ABSTRACT_PUBMED_21895609}}		{{ABSTRACT_PUBMED_21895609}}

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	==See Also==		==See Also==
-	*[[Ionotropic Glutamate Receptors]]	+	*[[Ionotropic Glutamate Receptors\|Ionotropic Glutamate Receptors]]

	==Reference==		==Reference==

OCA at 06:24, 28 December 2011

OCA — Wed, 28 Dec 2011 06:24:51 GMT

←Older revision		Revision as of 06:24, 28 December 2011
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-	[[Image:3tkd.~~jpg~~\|left\|200px]]	+	[[Image:3tkd.png\|left\|200px]]

	<!--		<!--
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	==About this Structure==		==About this Structure==
-	[[3tkd]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TKD OCA].	+	[[3tkd]] is a 2 chain structure of [[Ionotropic Glutamate Receptors]] with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TKD OCA].
		+
		+	==See Also==
		+	*[[Ionotropic Glutamate Receptors]]

	==Reference==		==Reference==

OCA at 06:01, 21 September 2011

OCA — Wed, 21 Sep 2011 06:01:43 GMT

←Older revision		Revision as of 06:01, 21 September 2011
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-	~~'''Unreleased structure'''~~	+	[[Image:3tkd.jpg\|left\|200px]]

-	The ~~entry 3tkd~~ is ~~ON HOLD~~	+	<!--
		+	The line below this paragraph, containing "STRUCTURE_3tkd", 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_3tkd\| PDB=3tkd \| SCENE= }}

-	~~Authors: Krintel, C., Frydenvang, K., Gajhede, M., Kastrup, J.S~~.	+	===Crystal structure of the GluA2 ligand-binding domain (S1S2J-L483Y-N754S) in complex with glutamate and cyclothiazide at 1.45 A resolution===

-	~~Description~~: ~~Crystal structure of~~ the ~~GLUA2~~ ligand-binding domain ~~(S1S2J~~-~~L483Y~~-~~N754S) in complex with glutamate and cyclothiazide at 1.45 A resolution~~	+
		+	<!--
		+	The line below this paragraph, {{ABSTRACT_PUBMED_21895609}}, adds the Publication Abstract to the page
		+	(as it appears on PubMed at http://www.pubmed.gov), where 21895609 is the PubMed ID number.
		+	-->
		+	{{ABSTRACT_PUBMED_21895609}}
		+
		+	==About this Structure==
		+	[[3tkd]] is a 2 chain structure with sequence from [http://en.wikipedia.org/wiki/Rattus_norvegicus Rattus norvegicus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=3TKD OCA].
		+
		+	==Reference==
		+	<ref group="xtra">PMID:021895609</ref><ref group="xtra">PMID:012015593</ref><references group="xtra"/>
		+	[[Category: Rattus norvegicus]]
		+	[[Category: Frydenvang, K.]]
		+	[[Category: Gajhede, M.]]
		+	[[Category: Kastrup, J S.]]
		+	[[Category: Krintel, C.]]
		+	[[Category: Allosteric modulation]]
		+	[[Category: Ampa receptor ligand-binding domain]]
		+	[[Category: Cyclothiazide]]
		+	[[Category: Glua2 s1s2j-l483y-n754]]
		+	[[Category: Membrane protein]]

OCA at 06:04, 14 September 2011

OCA — Wed, 14 Sep 2011 06:04:46 GMT

←Older revision		Revision as of 06:04, 14 September 2011
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	Authors: Krintel, C., Frydenvang, K., Gajhede, M., Kastrup, J.S.		Authors: Krintel, C., Frydenvang, K., Gajhede, M., Kastrup, J.S.

-	Description: ~~CRYSTAL STRUCTURE OF THE~~ GLUA2 ~~LIGAND~~-~~BINDING DOMAIN~~ (S1S2J-L483Y-N754S) ~~IN COMPLEX WITH GLUTAMATE AND CYCLOTHIAZIDE AT~~ 1.45 A ~~RESOLUTION~~	+	Description: Crystal structure of the GLUA2 ligand-binding domain (S1S2J-L483Y-N754S) in complex with glutamate and cyclothiazide at 1.45 A resolution