7tti - Revision history

OCA at 14:05, 6 November 2024

2024-11-06T14:05:06Z

← Older revision		Revision as of 14:05, 6 November 2024
Line 4:		Line 4:
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7tti]] 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=7TTI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TTI FirstGlance]. <br>		<table><tr><td colspan='2'>[[7tti]] 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=7TTI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TTI FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JUX:N-cyclopropyl-N-(4-methyl-1,3-thiazol-2-yl)-2-[(6-phenylpyridazin-3-yl)sulfanyl~~]acetamide~~'>JUX</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>		</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models\|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution\|Resolution]] 3.5Å</td></tr>
			<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JUX:~{N}-cyclopropyl-~{N}-(4-methyl-1,3-thiazol-2-yl)-2-(6-phenylpyridazin-3-yl)sulfanyl-ethanamide'>JUX</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=7tti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tti OCA], [https://pdbe.org/7tti PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tti RCSB], [https://www.ebi.ac.uk/pdbsum/7tti PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tti 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=7tti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tti OCA], [https://pdbe.org/7tti PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tti RCSB], [https://www.ebi.ac.uk/pdbsum/7tti PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tti ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/S12A4_HUMAN S12A4_HUMAN]] Mediates electroneutral potassium-chloride cotransport when activated by cell swelling. May contribute to cell volume homeostasis in single cells. May be involved in the regulation of basolateral Cl(-) exit in NaCl absorbing epithelia (By similarity). Isoform 4 has no transport activity.		[https://www.uniprot.org/uniprot/S12A4_HUMAN S12A4_HUMAN] Mediates electroneutral potassium-chloride cotransport when activated by cell swelling. May contribute to cell volume homeostasis in single cells. May be involved in the regulation of basolateral Cl(-) exit in NaCl absorbing epithelia (By similarity). Isoform 4 has no transport activity.
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Cation-chloride cotransporters (CCCs) catalyze electroneutral symport of Cl(-) with Na(+) and/or K(+) across membranes. CCCs are fundamental in cell volume homeostasis, transepithelia ion movement, maintenance of intracellular Cl(-) concentration, and neuronal excitability. Here, we present a cryoelectron microscopy structure of human K(+)-Cl(-) cotransporter (KCC)1 bound with the VU0463271 inhibitor in an outward-open state. In contrast to many other amino acid-polyamine-organocation transporter cousins, our first outward-open CCC structure reveals that opening the KCC1 extracellular ion permeation path does not involve hinge-bending motions of the transmembrane (TM) 1 and TM6 half-helices. Instead, rocking of TM3 and TM8, together with displacements of TM4, TM9, and a conserved intracellular loop 1 helix, underlie alternate opening and closing of extracellular and cytoplasmic vestibules. We show that KCC1 intriguingly exists in one of two distinct dimeric states via different intersubunit interfaces. Our studies provide a blueprint for understanding the mechanisms of CCCs and their inhibition by small molecule compounds.

			Structure of the human cation-chloride cotransport KCC1 in an outward-open state.,Zhao Y, Shen J, Wang Q, Ruiz Munevar MJ, Vidossich P, De Vivo M, Zhou M, Cao E Proc Natl Acad Sci U S A. 2022 Jul 5;119(27):e2109083119. doi: , 10.1073/pnas.2109083119. Epub 2022 Jun 27. PMID:35759661<ref>PMID:35759661</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 7tti" style="background-color:#fffaf0;"></div>

			==See Also==
			*[[Solute carrier family 12 3D structures\|Solute carrier family 12 3D structures]]
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>

OCA at 06:26, 8 September 2022

2022-09-08T06:26:03Z

← Older revision		Revision as of 06:26, 8 September 2022
Line 3:		Line 3:
	<StructureSection load='7tti' size='340' side='right'caption='[[7tti]], [[Resolution\|resolution]] 3.50Å' scene=''>		<StructureSection load='7tti' size='340' side='right'caption='[[7tti]], [[Resolution\|resolution]] 3.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7tti]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TTI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TTI FirstGlance]. <br>		<table><tr><td colspan='2'>[[7tti]] 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=7TTI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TTI FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JUX:N-cyclopropyl-N-(4-methyl-1,3-thiazol-2-yl)-2-[(6-phenylpyridazin-3-yl)sulfanyl]acetamide'>JUX</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JUX:N-cyclopropyl-N-(4-methyl-1,3-thiazol-2-yl)-2-[(6-phenylpyridazin-3-yl)sulfanyl]acetamide'>JUX</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=7tti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tti OCA], [https://pdbe.org/7tti PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tti RCSB], [https://www.ebi.ac.uk/pdbsum/7tti PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tti 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=7tti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tti OCA], [https://pdbe.org/7tti PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tti RCSB], [https://www.ebi.ac.uk/pdbsum/7tti PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tti ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
	[[https://www.uniprot.org/uniprot/S12A4_HUMAN S12A4_HUMAN]] Mediates electroneutral potassium-chloride cotransport when activated by cell swelling. May contribute to cell volume homeostasis in single cells. May be involved in the regulation of basolateral Cl(-) exit in NaCl absorbing epithelia (By similarity). Isoform 4 has no transport activity.		[[https://www.uniprot.org/uniprot/S12A4_HUMAN S12A4_HUMAN]] Mediates electroneutral potassium-chloride cotransport when activated by cell swelling. May contribute to cell volume homeostasis in single cells. May be involved in the regulation of basolateral Cl(-) exit in NaCl absorbing epithelia (By similarity). Isoform 4 has no transport activity.
	~~<div style="background-color:#fffaf0;">~~
	~~== Publication Abstract from PubMed ==~~
	Cation-chloride cotransporters (CCCs) catalyze electroneutral symport of Cl(-) with Na(+) and/or K(+) across membranes. CCCs are fundamental in cell volume homeostasis, transepithelia ion movement, maintenance of intracellular Cl(-) concentration, and neuronal excitability. Here, we present a cryoelectron microscopy structure of human K(+)-Cl(-) cotransporter (KCC)1 bound with the VU0463271 inhibitor in an outward-open state. In contrast to many other amino acid-polyamine-organocation transporter cousins, our first outward-open CCC structure reveals that opening the KCC1 extracellular ion permeation path does not involve hinge-bending motions of the transmembrane (TM) 1 and TM6 half-helices. Instead, rocking of TM3 and TM8, together with displacements of TM4, TM9, and a conserved intracellular loop 1 helix, underlie alternate opening and closing of extracellular and cytoplasmic vestibules. We show that KCC1 intriguingly exists in one of two distinct dimeric states via different intersubunit interfaces. Our studies provide a blueprint for understanding the mechanisms of CCCs and their inhibition by small molecule compounds.

	Structure of the human cation-chloride cotransport KCC1 in an outward-open state.,Zhao Y, Shen J, Wang Q, Ruiz Munevar MJ, Vidossich P, De Vivo M, Zhou M, Cao E Proc Natl Acad Sci U S A. 2022 Jul 5;119(27):e2109083119. doi:, 10.1073/pnas.2109083119. Epub 2022 Jun 27. PMID:35759661<ref>PMID:35759661</ref>

	~~From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>~~
	~~</div>~~
	~~<div class="pdbe-citations 7tti" style="background-color:#fffaf0;"></div>~~
	~~== References ==~~
	~~<references/>~~
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
			[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: Cao~~, E H~~]]		[[Category: Cao EH]]
	[[Category: Zhao~~, Y X]]~~		[[Category: Zhao YX]]
	~~[[Category: Outward-open state]]~~
	~~[[Category: Slc12a4]]~~
	~~[[Category: Transport protein-inhibitor complex]]~~
	~~[[Category: Vu0463271~~]]

OCA at 05:27, 13 July 2022

2022-07-13T05:27:24Z

← Older revision		Revision as of 05:27, 13 July 2022
Line 1:		Line 1:

	==~~n/a~~==		==Human KCC1 bound with VU0463271 In an outward-open state==
	<StructureSection load='7tti' size='340' side='right'caption='[[7tti]]' scene=''>		<StructureSection load='7tti' size='340' side='right'caption='[[7tti]], [[Resolution\|resolution]] 3.50Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TTI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TTI FirstGlance]. <br>		<table><tr><td colspan='2'>[[7tti]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TTI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TTI FirstGlance]. <br>
	</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=7tti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tti OCA], [https://pdbe.org/7tti PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tti RCSB], [https://www.ebi.ac.uk/pdbsum/7tti PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tti ProSAT]</span></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=JUX:N-cyclopropyl-N-(4-methyl-1,3-thiazol-2-yl)-2-[(6-phenylpyridazin-3-yl)sulfanyl]acetamide'>JUX</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene></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=7tti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tti OCA], [https://pdbe.org/7tti PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tti RCSB], [https://www.ebi.ac.uk/pdbsum/7tti PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tti ProSAT]</span></td></tr>
	</table>		</table>
			== Function ==
			[[https://www.uniprot.org/uniprot/S12A4_HUMAN S12A4_HUMAN]] Mediates electroneutral potassium-chloride cotransport when activated by cell swelling. May contribute to cell volume homeostasis in single cells. May be involved in the regulation of basolateral Cl(-) exit in NaCl absorbing epithelia (By similarity). Isoform 4 has no transport activity.
			<div style="background-color:#fffaf0;">
			== Publication Abstract from PubMed ==
			Cation-chloride cotransporters (CCCs) catalyze electroneutral symport of Cl(-) with Na(+) and/or K(+) across membranes. CCCs are fundamental in cell volume homeostasis, transepithelia ion movement, maintenance of intracellular Cl(-) concentration, and neuronal excitability. Here, we present a cryoelectron microscopy structure of human K(+)-Cl(-) cotransporter (KCC)1 bound with the VU0463271 inhibitor in an outward-open state. In contrast to many other amino acid-polyamine-organocation transporter cousins, our first outward-open CCC structure reveals that opening the KCC1 extracellular ion permeation path does not involve hinge-bending motions of the transmembrane (TM) 1 and TM6 half-helices. Instead, rocking of TM3 and TM8, together with displacements of TM4, TM9, and a conserved intracellular loop 1 helix, underlie alternate opening and closing of extracellular and cytoplasmic vestibules. We show that KCC1 intriguingly exists in one of two distinct dimeric states via different intersubunit interfaces. Our studies provide a blueprint for understanding the mechanisms of CCCs and their inhibition by small molecule compounds.

			Structure of the human cation-chloride cotransport KCC1 in an outward-open state.,Zhao Y, Shen J, Wang Q, Ruiz Munevar MJ, Vidossich P, De Vivo M, Zhou M, Cao E Proc Natl Acad Sci U S A. 2022 Jul 5;119(27):e2109083119. doi:, 10.1073/pnas.2109083119. Epub 2022 Jun 27. PMID:35759661<ref>PMID:35759661</ref>

			From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
			</div>
			<div class="pdbe-citations 7tti" style="background-color:#fffaf0;"></div>
			== References ==
			<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
	[[Category: ~~N/a~~]]		[[Category: Cao, E H]]
			[[Category: Zhao, Y X]]
			[[Category: Outward-open state]]
			[[Category: Slc12a4]]
			[[Category: Transport protein-inhibitor complex]]
			[[Category: Vu0463271]]

OCA at 07:27, 29 June 2022

2022-06-29T07:27:50Z

← Older revision		Revision as of 07:27, 29 June 2022
Line 1:		Line 1:
	~~'''Unreleased structure'''~~

	~~The entry~~ 7tti is ~~ON HOLD until Paper Publication~~		==n/a==
			<StructureSection load='7tti' size='340' side='right'caption='[[7tti]]' scene=''>
	~~Authors:~~		== Structural highlights ==
			<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7TTI OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7TTI FirstGlance]. <br>
	~~Description~~:		</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=7tti FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7tti OCA], [https://pdbe.org/7tti PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7tti RCSB], [https://www.ebi.ac.uk/pdbsum/7tti PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7tti ProSAT]</span></td></tr>
	[[Category: ~~Unreleased Structures~~]]		</table>
			__TOC__
			</StructureSection>
			[[Category: Large Structures]]
			[[Category: N/a]]

OCA at 04:53, 9 March 2022

2022-03-09T04:53:15Z

← Older revision		Revision as of 04:53, 9 March 2022
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

	The entry 7tti is ON HOLD		The entry 7tti is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7tti" [edit=sysop:move=sysop]

2022-02-09T06:21:12Z

Protected "7tti" [edit=sysop:move=sysop]

← Older revision	Revision as of 06:21, 9 February 2022
(No difference)

OCA: New page: '''Unreleased structure''' The entry 7tti is ON HOLD Authors: Description: Category: Unreleased Structures

2022-02-09T06:21:11Z

New page: '''Unreleased structure''' The entry 7tti is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7tti is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]