View source for 8x43


==human KCNQ2-CaM-Ebio1-S1 complex in the presence of PIP2==
<StructureSection load='8x43' size='340' side='right'caption='[[8x43]], [[Resolution|resolution]] 3.00&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8x43]] is a 8 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=8X43 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8X43 FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=7Q0:N-(4-azanyl-1,2-dihydroacenaphthylen-5-yl)-4-fluoranyl-benzamide'>7Q0</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=8x43 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8x43 OCA], [https://pdbe.org/8x43 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8x43 RCSB], [https://www.ebi.ac.uk/pdbsum/8x43 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8x43 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/KCNQ2_HUMAN KCNQ2_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Pharmacological activation of voltage-gated ion channels by ligands serves as the basis for therapy and mainly involves a classic gating mechanism that augments the native voltage-dependent open probability. Through structure-based virtual screening, we identified a new scaffold compound, Ebio1, serving as a potent and subtype-selective activator for the voltage-gated potassium channel KCNQ2 and featuring a new activation mechanism. Single-channel patch-clamp, cryogenic-electron microscopy and molecular dynamic simulations, along with chemical derivatives, reveal that Ebio1 engages the KCNQ2 activation by generating an extended channel gate with a larger conductance at the saturating voltage (+50 mV). This mechanism is different from the previously observed activation mechanism of ligands on voltage-gated ion channels. Ebio1 caused S6 helices from residues S303 and F305 to perform a twist-to-open movement, which was sufficient to open the KCNQ2 gate. Overall, our findings provide mechanistic insights into the activation of KCNQ2 channel by Ebio1 and lend support for KCNQ-related drug development.

A small-molecule activation mechanism that directly opens the KCNQ2 channel.,Zhang S, Ma D, Wang K, Li Y, Yang Z, Li X, Li J, He J, Mei L, Ye Y, Chen Z, Shen J, Hou P, Guo J, Zhang Q, Yang H Nat Chem Biol. 2024 Jul;20(7):847-856. doi: 10.1038/s41589-023-01515-y. Epub 2024 , Jan 2. PMID:38167918<ref>PMID:38167918</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8x43" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Guo J]]
[[Category: Ma D]]