OCA at 06:13, 2 March 2023

OCA — Thu, 02 Mar 2023 06:13:23 GMT

←Older revision		Revision as of 06:13, 2 March 2023
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-	====	+	==Nav1.7 mutant class2==
-	<StructureSection load='7xvf' size='340' side='right'caption='[[7xvf]]' scene=''>	+	<StructureSection load='7xvf' size='340' side='right'caption='[[7xvf]], [[Resolution\|resolution]] 2.80Å' 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= OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol= FirstGlance]. <br>	+	<table><tr><td colspan='2'>[[7xvf]] is a 3 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=7XVF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XVF 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=7xvf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xvf OCA], [https://pdbe.org/7xvf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xvf RCSB], [https://www.ebi.ac.uk/pdbsum/7xvf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xvf 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=1PW:(2S,3R,4E)-2-(ACETYLAMINO)-3-HYDROXYOCTADEC-4-EN-1-YL+DIHYDROGEN+PHOSPHATE'>1PW</scene>, <scene name='pdbligand=CLR:CHOLESTEROL'>CLR</scene>, <scene name='pdbligand=LPE:1-O-OCTADECYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>LPE</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=P5S:O-[(R)-{[(2R)-2,3-BIS(OCTADECANOYLOXY)PROPYL]OXY}(HYDROXY)PHOSPHORYL]-L-SERINE'>P5S</scene>, <scene name='pdbligand=PCW:1,2-DIOLEOYL-SN-GLYCERO-3-PHOSPHOCHOLINE'>PCW</scene>, <scene name='pdbligand=Y01:CHOLESTEROL+HEMISUCCINATE'>Y01</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=7xvf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xvf OCA], [https://pdbe.org/7xvf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xvf RCSB], [https://www.ebi.ac.uk/pdbsum/7xvf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xvf ProSAT]</span></td></tr>
	</table>		</table>
		+	== Disease ==
		+	[https://www.uniprot.org/uniprot/SCN9A_HUMAN SCN9A_HUMAN] Channelopathy-associated congenital insensitivity to pain;Dravet syndrome;Primary erythromelalgia;Sodium channelopathy-related small fiber neuropathy;Generalized epilepsy with febrile seizures-plus;Hereditary sensory and autonomic neuropathy type 2;Paroxysmal extreme pain disorder;Erythromelalgia. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
		+	== Function ==
		+	[https://www.uniprot.org/uniprot/SCN9A_HUMAN SCN9A_HUMAN] Mediates the voltage-dependent sodium ion permeability of excitable membranes. Assuming opened or closed conformations in response to the voltage difference across the membrane, the protein forms a sodium-selective channel through which Na(+) ions may pass in accordance with their electrochemical gradient (PubMed:7720699, PubMed:17167479, PubMed:25240195, PubMed:26680203, PubMed:15385606, PubMed:16988069, PubMed:17145499, PubMed:19369487, PubMed:24311784). It is a tetrodotoxin-sensitive Na(+) channel isoform (PubMed:7720699). Plays a role in pain mechanisms, especially in the development of inflammatory pain (PubMed:17167479, PubMed:17145499, PubMed:19369487, PubMed:24311784).<ref>PMID:15178348</ref> <ref>PMID:15385606</ref> <ref>PMID:16988069</ref> <ref>PMID:17145499</ref> <ref>PMID:17167479</ref> <ref>PMID:19369487</ref> <ref>PMID:24311784</ref> <ref>PMID:25240195</ref> <ref>PMID:26680203</ref> <ref>PMID:7720699</ref>
		+	<div style="background-color:#fffaf0;">
		+	== Publication Abstract from PubMed ==
		+	Voltage-gated sodium (Na(v)) channel Na(v)1.7 has been targeted for the development of nonaddictive pain killers. Structures of Na(v)1.7 in distinct functional states will offer an advanced mechanistic understanding and aid drug discovery. Here we report the cryoelectron microscopy analysis of a human Na(v)1.7 variant that, with 11 rationally introduced point mutations, has a markedly right-shifted activation voltage curve with V(1/2) reaching 69 mV. The voltage-sensing domain in the first repeat (VSD(I)) in a 2.7-A resolution structure displays a completely down (deactivated) conformation. Compared to the structure of WT Na(v)1.7, three gating charge (GC) residues in VSD(I) are transferred to the cytosolic side through a combination of helix unwinding and spiral sliding of S4(I) and approximately 20 degrees domain rotation. A conserved WNcapital EF, Cyrilliccapital EF, CyrillicD motif on the cytoplasmic end of S3(I) stabilizes the down conformation of VSD(I). One GC residue is transferred in VSD(II) mainly through helix sliding. Accompanying GC transfer in VSD(I) and VSD(II), rearrangement and contraction of the intracellular gate is achieved through concerted movements of adjacent segments, including S4-5(I), S4-5(II), S5(II), and all S6 segments. Our studies provide important insight into the electromechanical coupling mechanism of the single-chain voltage-gated ion channels and afford molecular interpretations for a number of pain-associated mutations whose pathogenic mechanism cannot be revealed from previously reported Na(v) structures.
		+
		+	Unwinding and spiral sliding of S4 and domain rotation of VSD during the electromechanical coupling in Na(v)1.7.,Huang G, Wu Q, Li Z, Jin X, Huang X, Wu T, Pan X, Yan N Proc Natl Acad Sci U S A. 2022 Aug 16;119(33):e2209164119. doi: , 10.1073/pnas.2209164119. Epub 2022 Jul 25. PMID:35878056<ref>PMID:35878056</ref>
		+
		+	From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br>
		+	</div>
		+	<div class="pdbe-citations 7xvf" style="background-color:#fffaf0;"></div>
		+	== References ==
		+	<references/>
	__TOC__		__TOC__
	</StructureSection>		</StructureSection>
		+	[[Category: Homo sapiens]]
	[[Category: Large Structures]]		[[Category: Large Structures]]
-	[[Category: Z~~-disk~~]]	+	[[Category: Huang G]]
		+	[[Category: Li Z]]
		+	[[Category: Pan X]]
		+	[[Category: Wu Q]]
		+	[[Category: Yan N]]

OCA at 05:02, 10 August 2022

OCA — Wed, 10 Aug 2022 05:02:36 GMT

←Older revision		Revision as of 05:02, 10 August 2022
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-	'''Unreleased structure'''

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

OCA at 03:35, 3 August 2022

OCA — Wed, 03 Aug 2022 03:35:46 GMT

←Older revision		Revision as of 03:35, 3 August 2022
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	'''Unreleased structure'''		'''Unreleased structure'''

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

	Authors:		Authors:

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

OCA — Wed, 08 Jun 2022 04:00:37 GMT

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

←Older revision

Revision as of 04:00, 8 June 2022

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

OCA — Wed, 08 Jun 2022 04:00:36 GMT

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

New page

'''Unreleased structure'''

The entry 7xvf is ON HOLD

Authors:

Description:
[[Category: Unreleased Structures]]

7xvf - Revision history

OCA at 06:13, 2 March 2023

OCA at 05:02, 10 August 2022

OCA at 03:35, 3 August 2022

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

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