7xmf

From Proteopedia

(Difference between revisions)
Jump to: navigation, search
Current revision (06:45, 25 June 2025) (edit) (undo)
 
Line 4: Line 4:
== Structural highlights ==
== Structural highlights ==
<table><tr><td colspan='2'>[[7xmf]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Aequorea_victoria Aequorea victoria] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7XMF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XMF FirstGlance]. <br>
<table><tr><td colspan='2'>[[7xmf]] is a 3 chain structure with sequence from [https://en.wikipedia.org/wiki/Aequorea_victoria Aequorea victoria] and [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7XMF OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XMF FirstGlance]. <br>
-
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G2W:3-[[4-[3-(4-fluoranyl-2-methyl-phenoxy)azetidin-1-yl]pyrimidin-2-yl]amino]-~{N}-methyl-benzamide'>G2W</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]] 3.07&#8491;</td></tr>
 +
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=G2W:3-[[4-[3-(4-fluoranyl-2-methyl-phenoxy)azetidin-1-yl]pyrimidin-2-yl]amino]-~{N}-methyl-benzamide'>G2W</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=7xmf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xmf OCA], [https://pdbe.org/7xmf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xmf RCSB], [https://www.ebi.ac.uk/pdbsum/7xmf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xmf 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=7xmf FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xmf OCA], [https://pdbe.org/7xmf PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xmf RCSB], [https://www.ebi.ac.uk/pdbsum/7xmf PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xmf ProSAT]</span></td></tr>
</table>
</table>
Line 11: Line 12:
== Function ==
== 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>
[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 channel Na(V)1.7 plays essential roles in pain and odor perception. Na(V)1.7 variants cause pain disorders. Accordingly, Na(V)1.7 has elicited extensive attention in developing new analgesics. Here we present cryo-EM structures of human Na(V)1.7/beta1/beta2 complexed with inhibitors XEN907, TC-N1752 and Na(V)1.7-IN2, explaining specific binding sites and modulation mechanism for the pore blockers. These inhibitors bind in the central cavity blocking ion permeation, but engage different parts of the cavity wall. XEN907 directly causes alpha- to pi-helix transition of DIV-S6 helix, which tightens the fast inactivation gate. TC-N1752 induces pi-helix transition of DII-S6 helix mediated by a conserved asparagine on DIII-S6, which closes the activation gate. Na(V)1.7-IN2 serves as a pore blocker without causing conformational change. Electrophysiological results demonstrate that XEN907 and TC-N1752 stabilize Na(V)1.7 in inactivated state and delay the recovery from inactivation. Our results provide structural framework for Na(V)1.7 modulation by pore blockers, and important implications for developing subtype-selective analgesics.
 +
 +
Structural basis for Na(V)1.7 inhibition by pore blockers.,Zhang J, Shi Y, Huang Z, Li Y, Yang B, Gong J, Jiang D Nat Struct Mol Biol. 2022 Dec;29(12):1208-1216. doi: 10.1038/s41594-022-00860-1. , Epub 2022 Nov 24. PMID:36424527<ref>PMID:36424527</ref>
 +
 +
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
 +
</div>
 +
<div class="pdbe-citations 7xmf" style="background-color:#fffaf0;"></div>
 +
 +
==See Also==
 +
*[[Green Fluorescent Protein 3D structures|Green Fluorescent Protein 3D structures]]
 +
*[[Ion channels 3D structures|Ion channels 3D structures]]
== References ==
== References ==
<references/>
<references/>

Current revision

Cryo-EM structure of human NaV1.7/beta1/beta2-Nav1.7-IN2

PDB ID 7xmf

Drag the structure with the mouse to rotate

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/7xmf"
Personal tools