5v03 - Revision history

OCA at 13:38, 4 October 2023

2023-10-04T13:38:07Z

←Older revision		Revision as of 13:38, 4 October 2023
Line 1:		Line 1:

	==A positive allosteric modulator binding pocket in SK2 ion channels is shared by Riluzole and CyPPA==		==A positive allosteric modulator binding pocket in SK2 ion channels is shared by Riluzole and CyPPA==
-	<StructureSection load='5v03' size='340' side='right' caption='[[5v03]], [[Resolution\|resolution]] 1.58Å' scene=''>	+	<StructureSection load='5v03' size='340' side='right'caption='[[5v03]], [[Resolution\|resolution]] 1.58Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5v03]] is a 2 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=5V03 OCA]. For a <b>guided tour on the structure components</b> use [~~http~~://~~oca~~.~~weizmann.ac.il/oca-docs~~/fgij/fg.htm?mol=5V03 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5v03]] is a 2 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=5V03 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=5V03 FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=658:N-(4-chlorophenyl)-2-(3,5-dimethyl-1H-pyrazol-1-yl)pyrimidin-4-amine'>658</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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]] 1.58Å</td></tr>
-	~~<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5v02\|5v02]]</td></tr>~~	+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=658:N-(4-chlorophenyl)-2-(3,5-dimethyl-1H-pyrazol-1-yl)pyrimidin-4-amine'>658</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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">KCNN2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CALM1, CALM, CAM, CAM1, CALM2, CAM2, CAMB, CALM3, CALML2, CAM3, CAMC, CAMIII ([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'>[https://proteopedia.org/fgij/fg.htm?mol=5v03 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v03 OCA], [https://pdbe.org/5v03 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=5v03 RCSB], [https://www.ebi.ac.uk/pdbsum/5v03 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=5v03 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=5v03 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v03 OCA], [~~http~~://pdbe.org/5v03 PDBe], [~~http~~://www.rcsb.org/pdb/explore.do?structureId=5v03 RCSB], [~~http~~://www.ebi.ac.uk/pdbsum/5v03 PDBsum], [~~http~~://prosat.h-its.org/prosat/prosatexe?pdbcode=5v03 ProSAT]</span></td></tr>	+
	</table>		</table>
	== Function ==		== Function ==
-	[~~[http~~://www.uniprot.org/uniprot/KCNN2_HUMAN KCNN2_HUMAN]] Forms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization. The channel is blocked by apamin.	+	[https://www.uniprot.org/uniprot/KCNN2_HUMAN KCNN2_HUMAN] Forms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization. The channel is blocked by apamin.
	<div style="background-color:#fffaf0;">		<div style="background-color:#fffaf0;">
	== Publication Abstract from PubMed ==		== Publication Abstract from PubMed ==
Line 22:		Line 21:

	==See Also==		==See Also==
-	*[[Calmodulin\|Calmodulin]]	+	*[[Calmodulin 3D structures\|Calmodulin 3D structures]]
		+	*[[Potassium channel 3D structures\|Potassium channel 3D structures]]
	== References ==		== References ==
	<references/>		<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
-	[[Category: ~~Human~~]]	+	[[Category: Homo sapiens]]
-	[[Category: ~~Liu, S~~]]	+	[[Category: Large Structures]]
-	[[Category: ~~Activator]]~~	+	[[Category: Liu S]]
-	~~[[Category: Calcium-activated ion channel]]~~	+
-	~~[[Category: Calmodulin]]~~	+
-	~~[[Category: Transport protein-metal binding protein complex~~]]	+

OCA at 05:53, 25 April 2018

2018-04-25T05:53:36Z

←Older revision		Revision as of 05:53, 25 April 2018
Line 3:		Line 3:
	<StructureSection load='5v03' size='340' side='right' caption='[[5v03]], [[Resolution\|resolution]] 1.58Å' scene=''>		<StructureSection load='5v03' size='340' side='right' caption='[[5v03]], [[Resolution\|resolution]] 1.58Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[5v03]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V03 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V03 FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[5v03]] is a 2 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=5V03 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V03 FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=658:N-(4-chlorophenyl)-2-(3,5-dimethyl-1H-pyrazol-1-yl)pyrimidin-4-amine'>658</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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=658:N-(4-chlorophenyl)-2-(3,5-dimethyl-1H-pyrazol-1-yl)pyrimidin-4-amine'>658</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</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">[[5v02\|5v02]]</td></tr>		<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5v02\|5v02]]</td></tr>
		+	<tr id='gene'><td class="sblockLbl"><b>[[Gene\|Gene:]]</b></td><td class="sblockDat">KCNN2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN]), CALM1, CALM, CAM, CAM1, CALM2, CAM2, CAMB, CALM3, CALML2, CAM3, CAMC, CAMIII ([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=5v03 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v03 OCA], [http://pdbe.org/5v03 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v03 RCSB], [http://www.ebi.ac.uk/pdbsum/5v03 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v03 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=5v03 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v03 OCA], [http://pdbe.org/5v03 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v03 RCSB], [http://www.ebi.ac.uk/pdbsum/5v03 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v03 ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[http://www.uniprot.org/uniprot/KCNN2_HUMAN KCNN2_HUMAN]] Forms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization. The channel is blocked by apamin.		[[http://www.uniprot.org/uniprot/KCNN2_HUMAN KCNN2_HUMAN]] Forms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization. The channel is blocked by apamin.
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Small conductance potassium (SK) ion channels define neuronal firing rates by conducting the after-hyperpolarization current. They are key targets in developing therapies where neuronal firing rates are dysfunctional, such as in epilepsy, Parkinson's, and amyotrophic lateral sclerosis (ALS). Here, we characterize a binding pocket situated at the intracellular interface of SK2 and calmodulin, which we show to be shared by multiple small-molecule chemotypes. Crystallization of this complex revealed that riluzole (approved for ALS) and an analog of the anti-ataxic agent (4-chloro-phenyl)-[2-(3,5-dimethyl-pyrazol-1-yl)-pyrimidin-4-yl]-amine (CyPPA) bind to and allosterically modulate via this site. Solution-state nuclear magnetic resonance demonstrates that riluzole, NS309, and CyPPA analogs bind at this bipartite pocket. We demonstrate, by patch-clamp electrophysiology, that both classes of ligand interact with overlapping but distinct residues within this pocket. These data define a clinically important site, laying the foundations for further studies of the mechanism of action of riluzole and related molecules.
		+
		+	An Intracellular Allosteric Modulator Binding Pocket in SK2 Ion Channels Is Shared by Multiple Chemotypes.,Cho LT, Alexandrou AJ, Torella R, Knafels J, Hobbs J, Taylor T, Loucif A, Konopacka A, Bell S, Stevens EB, Pandit J, Horst R, Withka JM, Pryde DC, Liu S, Young GT Structure. 2018 Apr 3;26(4):533-544.e3. doi: 10.1016/j.str.2018.02.017. Epub 2018, Mar 22. PMID:29576321<ref>PMID:29576321</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 5v03" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Calmodulin\|Calmodulin]]
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Human]]
	[[Category: Liu, S]]		[[Category: Liu, S]]
	[[Category: Activator]]		[[Category: Activator]]

OCA at 05:01, 8 March 2018

2018-03-08T05:01:16Z

←Older revision		Revision as of 05:01, 8 March 2018
Line 1:		Line 1:
-	'''Unreleased structure'''

-	~~The entry 5v03 is ON HOLD until Paper Publication~~	+	==A positive allosteric modulator binding pocket in SK2 ion channels is shared by Riluzole and CyPPA==
-		+	<StructureSection load='5v03' size='340' side='right' caption='[[5v03]], [[Resolution\|resolution]] 1.58Å' scene=''>
-	~~Authors: Liu, S.~~	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>[[5v03]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=5V03 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=5V03 FirstGlance]. <br>
-	~~Description:~~ A positive allosteric modulator binding pocket in SK2 ion channels is shared by Riluzole and CyPPA	+	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=658:N-(4-chlorophenyl)-2-(3,5-dimethyl-1H-pyrazol-1-yl)pyrimidin-4-amine'>658</scene>, <scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene></td></tr>
-	[[~~Category~~: ~~Unreleased Structures~~]]	+	<tr id='related'><td class="sblockLbl"><b>[[Related_structure\|Related:]]</b></td><td class="sblockDat">[[5v02\|5v02]]</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=5v03 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=5v03 OCA], [http://pdbe.org/5v03 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=5v03 RCSB], [http://www.ebi.ac.uk/pdbsum/5v03 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=5v03 ProSAT]</span></td></tr>
		+	</table>
		+	== Function ==
		+	[[http://www.uniprot.org/uniprot/KCNN2_HUMAN KCNN2_HUMAN]] Forms a voltage-independent potassium channel activated by intracellular calcium. Activation is followed by membrane hyperpolarization. Thought to regulate neuronal excitability by contributing to the slow component of synaptic afterhyperpolarization. The channel is blocked by apamin.
		+	__TOC__
		+	</StructureSection>
	[[Category: Liu, S]]		[[Category: Liu, S]]
		+	[[Category: Activator]]
		+	[[Category: Calcium-activated ion channel]]
		+	[[Category: Calmodulin]]
		+	[[Category: Transport protein-metal binding protein complex]]

OCA at 11:53, 27 April 2017

2017-04-27T11:53:24Z

←Older revision		Revision as of 11:53, 27 April 2017
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 5v03 is ON HOLD	+	The entry 5v03 is ON HOLD until Paper Publication

	Authors: Liu, S.		Authors: Liu, S.

OCA at 11:28, 5 April 2017

2017-04-05T11:28:30Z

←Older revision		Revision as of 11:28, 5 April 2017
Line 3:		Line 3:
	The entry 5v03 is ON HOLD		The entry 5v03 is ON HOLD

-	Authors: Liu,S~~, Liu,S, Liu,S~~	+	Authors: Liu, S.

	Description: A positive allosteric modulator binding pocket in SK2 ion channels is shared by Riluzole and CyPPA		Description: A positive allosteric modulator binding pocket in SK2 ion channels is shared by Riluzole and CyPPA
	[[Category: Unreleased Structures]]		[[Category: Unreleased Structures]]
-	[[Category: ~~Liu,S, Liu,S,~~ Liu,S]]	+	[[Category: Liu, S]]

OCA: Protected "5v03" [edit=sysop:move=sysop]

2017-03-09T15:10:19Z

Protected "5v03" [edit=sysop:move=sysop]

←Older revision

Revision as of 15:10, 9 March 2017

OCA: New page: '''Unreleased structure''' The entry 5v03 is ON HOLD Authors: Liu,S, Liu,S, Liu,S Description: A positive allosteric modulator binding pocket in SK2 ion channels is shared by Riluzole ...

2017-03-09T15:10:18Z

New page: '''Unreleased structure''' The entry 5v03 is ON HOLD Authors: Liu,S, Liu,S, Liu,S Description: A positive allosteric modulator binding pocket in SK2 ion channels is shared by Riluzole ...

New page

'''Unreleased structure'''

The entry 5v03 is ON HOLD

Authors: Liu,S, Liu,S, Liu,S

Description: A positive allosteric modulator binding pocket in SK2 ion channels is shared by Riluzole and CyPPA
[[Category: Unreleased Structures]]
[[Category: Liu,S, Liu,S, Liu,S]]