5mfw - Revision history

OCA at 18:42, 1 November 2023

OCA — Wed, 01 Nov 2023 18:42:30 GMT

←Older revision		Revision as of 18:42, 1 November 2023
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	==Crystal structure of the GluK1 ligand-binding domain in complex with kainate and BPAM-121 at 2.10 A resolution==		==Crystal structure of the GluK1 ligand-binding domain in complex with kainate and BPAM-121 at 2.10 A resolution==
-	<StructureSection load='5mfw' size='340' side='right' caption='[[5mfw]], [[Resolution\|resolution]] 2.10Å' scene=''>	+	<StructureSection load='5mfw' size='340' side='right'caption='[[5mfw]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5mfw]] 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=5MFW OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5MFW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5mfw]] 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=5MFW OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5MFW 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=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=KAI:3-(CARBOXYMETHYL)-4-ISOPROPENYLPROLINE'>KAI</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]] 2.1Å</td></tr>
-	~~<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">Grik1, Glur5 ([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=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=KAI:3-(CARBOXYMETHYL)-4-ISOPROPENYLPROLINE'>KAI</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=5mfw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mfw OCA], [~~http~~://pdbe.org/5mfw PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5mfw RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5mfw PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5mfw 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=5mfw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mfw OCA], [https://pdbe.org/5mfw PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5mfw RCSB], [https://www.ebi.ac.uk/pdbsum/5mfw PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5mfw ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/GRIK1_RAT GRIK1_RAT]] Ionotropic glutamate receptor. 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. May be involved in the transmission of light information from the retina to the hypothalamus.<ref>PMID:16540562</ref>	+	[https://www.uniprot.org/uniprot/GRIK1_RAT GRIK1_RAT] Ionotropic glutamate receptor. 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. May be involved in the transmission of light information from the retina to the hypothalamus.<ref>PMID:16540562</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 5mfw" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 5mfw" 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~~]]	+	[[Category: Rattus norvegicus]]
-	[[Category: ~~Kastrup, J S~~]]	+	[[Category: Frydenvang K]]
-	[[Category: ~~Larsen, A P~~]]	+	[[Category: Kastrup JS]]
-	[[Category: ~~Gluk1 ligand-binding domain]]~~	+	[[Category: Larsen AP]]
-	~~[[Category: Ionotropic glutamate receptor]]~~	+
-	~~[[Category: Membrane protein]]~~	+
-	~~[[Category: Positive allosteric modulator~~]]	+

OCA at 08:10, 17 January 2018

OCA — Wed, 17 Jan 2018 08:10:44 GMT

←Older revision		Revision as of 08:10, 17 January 2018
Line 3:		Line 3:
	<StructureSection load='5mfw' size='340' side='right' caption='[[5mfw]], [[Resolution\|resolution]] 2.10Å' scene=''>		<StructureSection load='5mfw' size='340' side='right' caption='[[5mfw]], [[Resolution\|resolution]] 2.10Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5mfw]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MFW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MFW FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5mfw]] 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=5MFW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MFW 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=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=KAI:3-(CARBOXYMETHYL)-4-ISOPROPENYLPROLINE'>KAI</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=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=KAI:3-(CARBOXYMETHYL)-4-ISOPROPENYLPROLINE'>KAI</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">Grik1, Glur5 ([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=5mfw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mfw OCA], [http://pdbe.org/5mfw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mfw RCSB], [http://www.ebi.ac.uk/pdbsum/5mfw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mfw 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=5mfw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mfw OCA], [http://pdbe.org/5mfw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mfw RCSB], [http://www.ebi.ac.uk/pdbsum/5mfw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mfw ProSAT]</span></td></tr>
	</table>		</table>
Line 22:		Line 23:
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Buffalo rat]]
	[[Category: Frydenvang, K]]		[[Category: Frydenvang, K]]
	[[Category: Kastrup, J S]]		[[Category: Kastrup, J S]]

OCA at 11:39, 12 April 2017

OCA — Wed, 12 Apr 2017 11:39:07 GMT

←Older revision		Revision as of 11:39, 12 April 2017
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry~~ 5mfw is ~~ON HOLD~~ ~~until Paper~~ Publication	+	==Crystal structure of the GluK1 ligand-binding domain in complex with kainate and BPAM-121 at 2.10 A resolution==
		+	<StructureSection load='5mfw' size='340' side='right' caption='[[5mfw]], [[Resolution\|resolution]] 2.10Å' scene=''>
		+	== Structural highlights ==
		+	<table><tr><td colspan='2'>[[5mfw]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5MFW OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5MFW 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=ACT:ACETATE+ION'>ACT</scene>, <scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=KAI:3-(CARBOXYMETHYL)-4-ISOPROPENYLPROLINE'>KAI</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=5mfw FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5mfw OCA], [http://pdbe.org/5mfw PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5mfw RCSB], [http://www.ebi.ac.uk/pdbsum/5mfw PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5mfw ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/GRIK1_RAT GRIK1_RAT]] Ionotropic glutamate receptor. 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. May be involved in the transmission of light information from the retina to the hypothalamus.<ref>PMID:16540562</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Kainate receptors (KARs) consist of a class of ionotropic glutamate receptors, which exert diverse pre- and postsynaptic functions through complex signaling regulating the activity of neural circuits. Whereas numerous small-molecule positive allosteric modulators of the ligand-binding domain of AMPA receptors have been reported, no such ligands are available for KARs. In this study, we have investigated the ability of three benzothiadiazine-based modulators to potentiate glutamate-evoked currents at recombinantly expressed KARs. BPAM344 potentiated glutamate-evoked currents of GluK2a 21-fold at the highest concentration tested (200 muM), with an EC50 of 79 muM. BPAM344 markedly decreased desensitization kinetics (from 5.5 to 775 ms), whereas it only had a minor effect on deactivation kinetics. BPAM521 potentiated the recorded peak current amplitude of GluK2a 12-fold at a concentration of 300 muM with an EC50 value of 159 muM, whereas no potentiation of the glutamate-evoked response was observed for BPAM121 at the highest concentration of modulator tested (300 muM). BPAM344 (100 muM) also potentiated the peak current amplitude of KAR subunits GluK3a (59-fold), GluK2a (15-fold), GluK1b (5-fold), as well as the AMPA receptor subunit GluA1i (5-fold). X-ray structures of the three modulators in the GluK1 ligand-binding domain were determined, locating two modulator-binding sites at the GluK1 dimer interface. In conclusion, this study opens for the design of new positive allosteric modulators selective for KARs, which will be of great interest for further investigating the function of KARs in vivo and may prove useful to phamacologically control the activity of neuronal networks.

-	~~Authors~~:	+	Identification and structure-function study of positive allosteric modulators of kainate receptors.,Larsen AP, Fievre S, Frydenvang K, Francotte P, Pirotte B, Karstrup JS, Mulle C Mol Pharmacol. 2017 Mar 30. pii: mol.116.107599. doi: 10.1124/mol.116.107599. PMID:28360094<ref>PMID:28360094</ref>

-	~~Description~~:	+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
-	[[Category: ~~Unreleased Structures~~]]	+	</div>
		+	<div class="pdbe-citations 5mfw" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Frydenvang, K]]
		+	[[Category: Kastrup, J S]]
		+	[[Category: Larsen, A P]]
		+	[[Category: Gluk1 ligand-binding domain]]
		+	[[Category: Ionotropic glutamate receptor]]
		+	[[Category: Membrane protein]]
		+	[[Category: Positive allosteric modulator]]

OCA at 16:14, 15 December 2016

OCA — Thu, 15 Dec 2016 16:14:57 GMT

←Older revision		Revision as of 16:14, 15 December 2016
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5mfw is ON HOLD	+	The entry 5mfw is ON HOLD until Paper Publication

	Authors:		Authors:

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

OCA — Fri, 09 Dec 2016 16:47:29 GMT

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

←Older revision

Revision as of 16:47, 9 December 2016

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

OCA — Fri, 09 Dec 2016 16:47:27 GMT

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

New page

'''Unreleased structure'''

The entry 5mfw is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]