7d2k - Revision history

OCA at 16:24, 29 November 2023

OCA — Wed, 29 Nov 2023 16:24:36 GMT

←Older revision		Revision as of 16:24, 29 November 2023
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	== Structural highlights ==		== Structural highlights ==
	<table><tr><td colspan='2'>[[7d2k]] is a 1 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=7D2K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7D2K FirstGlance]. <br>		<table><tr><td colspan='2'>[[7d2k]] is a 1 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=7D2K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7D2K FirstGlance]. <br>
-	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GQC:1-(5-bromanylpyridin-3-yl)-4-[4-(3-methylphenyl)cyclohexyl]piperazin-4-ium'>GQC</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]] 3.698Å</td></tr>
		+	<tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GQC:1-(5-bromanylpyridin-3-yl)-4-[4-(3-methylphenyl)cyclohexyl]piperazin-4-ium'>GQC</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=7d2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7d2k OCA], [https://pdbe.org/7d2k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7d2k RCSB], [https://www.ebi.ac.uk/pdbsum/7d2k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7d2k 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=7d2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7d2k OCA], [https://pdbe.org/7d2k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7d2k RCSB], [https://www.ebi.ac.uk/pdbsum/7d2k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7d2k ProSAT]</span></td></tr>
	</table>		</table>
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	</div>		</div>
	<div class="pdbe-citations 7d2k" style="background-color:#fffaf0;"></div>		<div class="pdbe-citations 7d2k" style="background-color:#fffaf0;"></div>
		+
		+	==See Also==
		+	*[[Ion channels 3D structures\|Ion channels 3D structures]]
	== References ==		== References ==
	<references/>		<references/>

OCA at 09:36, 19 April 2023

OCA — Wed, 19 Apr 2023 09:36:51 GMT

←Older revision		Revision as of 09:36, 19 April 2023
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	<StructureSection load='7d2k' size='340' side='right'caption='[[7d2k]], [[Resolution\|resolution]] 3.70Å' scene=''>		<StructureSection load='7d2k' size='340' side='right'caption='[[7d2k]], [[Resolution\|resolution]] 3.70Å' scene=''>
	== Structural highlights ==		== Structural highlights ==
-	<table><tr><td colspan='2'>[[7d2k]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7D2K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7D2K FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7d2k]] is a 1 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=7D2K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7D2K FirstGlance]. <br>
	</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GQC:1-(5-bromanylpyridin-3-yl)-4-[4-(3-methylphenyl)cyclohexyl]piperazin-4-ium'>GQC</scene></td></tr>		</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand\|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GQC:1-(5-bromanylpyridin-3-yl)-4-[4-(3-methylphenyl)cyclohexyl]piperazin-4-ium'>GQC</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=7d2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7d2k OCA], [https://pdbe.org/7d2k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7d2k RCSB], [https://www.ebi.ac.uk/pdbsum/7d2k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7d2k 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=7d2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7d2k OCA], [https://pdbe.org/7d2k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7d2k RCSB], [https://www.ebi.ac.uk/pdbsum/7d2k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7d2k ProSAT]</span></td></tr>
	</table>		</table>
	== Function ==		== Function ==
-	[[https://www.uniprot.org/uniprot/TRPV6_RAT TRPV6_RAT]] Calcium selective cation channel probably involved in Ca(2+) uptake in various tissues, including Ca(2+) reabsorption in intestine. The channel is activated by low internal calcium level, probably including intracellular calcium store depletion, and the current exhibits an inward rectification. Inactivation includes both, a rapid Ca(2+)-dependent and a slower Ca(2+)-calmodulin-dependent mechanism, the latter may be regulated by phosphorylation. In vitro, is slowly inhibited by Mg(2+) in a voltage-independent manner. Heteromeric assembly with TRPV5 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating (By similarity).[UniProtKB:Q91WD2][UniProtKB:Q9H1D0]<ref>PMID:11287959</ref>	+	[https://www.uniprot.org/uniprot/TRPV6_RAT TRPV6_RAT] Calcium selective cation channel probably involved in Ca(2+) uptake in various tissues, including Ca(2+) reabsorption in intestine. The channel is activated by low internal calcium level, probably including intracellular calcium store depletion, and the current exhibits an inward rectification. Inactivation includes both, a rapid Ca(2+)-dependent and a slower Ca(2+)-calmodulin-dependent mechanism, the latter may be regulated by phosphorylation. In vitro, is slowly inhibited by Mg(2+) in a voltage-independent manner. Heteromeric assembly with TRPV5 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating (By similarity).[UniProtKB:Q91WD2][UniProtKB:Q9H1D0]<ref>PMID:11287959</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Epithelial calcium channel TRPV6 plays vital roles in calcium homeostasis, and its dysregulation is implicated in multifactorial diseases, including cancers. Here, we study the molecular mechanism of selective nanomolar-affinity TRPV6 inhibition by (4-phenylcyclohexyl)piperazine derivatives (PCHPDs). We use x-ray crystallography and cryo-electron microscopy to solve the inhibitor-bound structures of TRPV6 and identify two types of inhibitor binding sites in the transmembrane region: (i) modulatory sites between the S1-S4 and pore domains normally occupied by lipids and (ii) the main site in the ion channel pore. Our structural data combined with mutagenesis, functional and computational approaches suggest that PCHPDs plug the open pore of TRPV6 and convert the channel into a nonconducting state, mimicking the action of calmodulin, which causes inactivation of TRPV6 channels under physiological conditions. This mechanism of inhibition explains the high selectivity and potency of PCHPDs and opens up unexplored avenues for the design of future-generation biomimetic drugs.
		+
		+	Inactivation-mimicking block of the epithelial calcium channel TRPV6.,Bhardwaj R, Lindinger S, Neuberger A, Nadezhdin KD, Singh AK, Cunha MR, Derler I, Gyimesi G, Reymond JL, Hediger MA, Romanin C, Sobolevsky AI Sci Adv. 2020 Nov 27;6(48). pii: 6/48/eabe1508. doi: 10.1126/sciadv.abe1508., Print 2020 Nov. PMID:33246965<ref>PMID:33246965</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7d2k" style="background-color:#fffaf0;"></div>
	== References ==		== References ==
	<references/>		<references/>
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	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: ~~Nadezhdin, K D~~]]	+	[[Category: Rattus norvegicus]]
-	[[Category: ~~Neuberger, A~~]]	+	[[Category: Nadezhdin KD]]
-	[[Category: ~~Singh,~~ A K]]	+	[[Category: Neuberger A]]
-	[[Category: ~~Sobolevsky, A I~~]]	+	[[Category: Singh AK]]
-	[[Category: ~~Ion channel]]~~	+	[[Category: Sobolevsky AI]]
-	~~[[Category: Membrane protein]]~~	+
-	~~[[Category: Transport protein-inhibitor complex]]~~	+
-	~~[[Category: Trp channel~~]]	+

OCA at 20:13, 20 October 2021

OCA — Wed, 20 Oct 2021 20:13:25 GMT

←Older revision		Revision as of 20:13, 20 October 2021
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	==Crystal structure of rat TRPV6 in complex with (4- phenylcyclohexyl)piperazine inhibitor Br-cis-22a==		==Crystal structure of rat TRPV6 in complex with (4- phenylcyclohexyl)piperazine inhibitor Br-cis-22a==
-	<StructureSection load='7d2k' size='340' side='right'caption='[[7d2k]]' scene=''>	+	<StructureSection load='7d2k' size='340' side='right'caption='[[7d2k]], [[Resolution\|resolution]] 3.70Å' 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=7D2K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7D2K FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7d2k]] is a 1 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7D2K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7D2K 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=7d2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7d2k OCA], [https://pdbe.org/7d2k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7d2k RCSB], [https://www.ebi.ac.uk/pdbsum/7d2k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7d2k 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=CA:CALCIUM+ION'>CA</scene>, <scene name='pdbligand=GQC:1-(5-bromanylpyridin-3-yl)-4-[4-(3-methylphenyl)cyclohexyl]piperazin-4-ium'>GQC</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=7d2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7d2k OCA], [https://pdbe.org/7d2k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7d2k RCSB], [https://www.ebi.ac.uk/pdbsum/7d2k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7d2k ProSAT]</span></td></tr>
	</table>		</table>
		+	== Function ==
		+	[[https://www.uniprot.org/uniprot/TRPV6_RAT TRPV6_RAT]] Calcium selective cation channel probably involved in Ca(2+) uptake in various tissues, including Ca(2+) reabsorption in intestine. The channel is activated by low internal calcium level, probably including intracellular calcium store depletion, and the current exhibits an inward rectification. Inactivation includes both, a rapid Ca(2+)-dependent and a slower Ca(2+)-calmodulin-dependent mechanism, the latter may be regulated by phosphorylation. In vitro, is slowly inhibited by Mg(2+) in a voltage-independent manner. Heteromeric assembly with TRPV5 seems to modify channel properties. TRPV5-TRPV6 heteromultimeric concatemers exhibit voltage-dependent gating (By similarity).[UniProtKB:Q91WD2][UniProtKB:Q9H1D0]<ref>PMID:11287959</ref>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Nadezhdin KD]]	+	[[Category: Nadezhdin, K D]]
-	[[Category: Neuberger A]]	+	[[Category: Neuberger, A]]
-	[[Category: ~~Sbolevsky AI~~]]	+	[[Category: Singh, A K]]
-	[[Category: ~~Singh AK~~]]	+	[[Category: Sobolevsky, A I]]
		+	[[Category: Ion channel]]
		+	[[Category: Membrane protein]]
		+	[[Category: Transport protein-inhibitor complex]]
		+	[[Category: Trp channel]]

OCA at 05:29, 6 October 2021

OCA — Wed, 06 Oct 2021 05:29:11 GMT

←Older revision		Revision as of 05:29, 6 October 2021
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-	'''Unreleased structure'''

-	~~The entry~~ 7d2k is ~~ON HOLD until Paper Publication~~	+	==Crystal structure of rat TRPV6 in complex with (4- phenylcyclohexyl)piperazine inhibitor Br-cis-22a==
-		+	<StructureSection load='7d2k' size='340' side='right'caption='[[7d2k]]' scene=''>
-	~~Authors~~:	+	== Structural highlights ==
-		+	<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7D2K OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7D2K 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=7d2k FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7d2k OCA], [https://pdbe.org/7d2k PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7d2k RCSB], [https://www.ebi.ac.uk/pdbsum/7d2k PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7d2k ProSAT]</span></td></tr>
-	[[Category: ~~Unreleased Structures~~]]	+	</table>
		+	__TOC__
		+	</StructureSection>
		+	[[Category: Large Structures]]
		+	[[Category: Nadezhdin KD]]
		+	[[Category: Neuberger A]]
		+	[[Category: Sbolevsky AI]]
		+	[[Category: Singh AK]]

OCA at 04:34, 7 October 2020

OCA — Wed, 07 Oct 2020 04:34:46 GMT

←Older revision		Revision as of 04:34, 7 October 2020
Line 1:		Line 1:
	'''Unreleased structure'''		'''Unreleased structure'''

-	The entry 7d2k is ON HOLD	+	The entry 7d2k is ON HOLD until Paper Publication

	Authors:		Authors:

OCA: Protected "7d2k" [edit=sysop:move=sysop]

OCA — Wed, 23 Sep 2020 08:58:53 GMT

Protected "7d2k" [edit=sysop:move=sysop]

←Older revision

Revision as of 08:58, 23 September 2020

OCA: New page: '''Unreleased structure''' The entry 7d2k is ON HOLD Authors: Description: Category: Unreleased Structures

OCA — Wed, 23 Sep 2020 08:58:52 GMT

New page: '''Unreleased structure''' The entry 7d2k is ON HOLD Authors: Description: Category: Unreleased Structures

New page

'''Unreleased structure'''

The entry 7d2k is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]