View source for 9xed


==Human KCNQ2-CaM in complex with QO-83 and PIP2==
<StructureSection load='9xed' size='340' side='right'caption='[[9xed]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9xed]] 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=9XED OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9XED 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]] 3.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=A1LWZ:~{N}-[2-azanyl-3-fluoranyl-4-[[4-(trifluoromethyl)phenyl]methylamino]phenyl]-3-cyclopentyl-propanamide'>A1LWZ</scene>, <scene name='pdbligand=PIO:[(2R)-2-OCTANOYLOXY-3-[OXIDANYL-[(1R,2R,3S,4R,5R,6S)-2,3,6-TRIS(OXIDANYL)-4,5-DIPHOSPHONOOXY-CYCLOHEXYL]OXY-PHOSPHORYL]OXY-PROPYL]+OCTANOATE'>PIO</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=9xed FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9xed OCA], [https://pdbe.org/9xed PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9xed RCSB], [https://www.ebi.ac.uk/pdbsum/9xed PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9xed ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/KCNQ2_HUMAN KCNQ2_HUMAN] 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The voltage-gated potassium channel KCNQ2 is crucial for stabilizing neuronal membrane potential, and its mutations can cause various epilepsies. KCNQ2 is activated by endogenous ligand phosphatidylinositol-4,5-bisphosphate (PIP(2)) and exogenous ligands, yet the structural mechanisms underlying these activations remain unclear. Here, we report the cryo-electron microscopy structures of human KCNQ2 in complex with exogenous ligands QO-58 and QO-83 in the absence or presence of PIP(2) in either closed or open conformation. While QO-83 binds in the classical fenestration pocket of the pore domain, QO-58 mainly binds at the flank of S4 in the voltage-sensing domain. These structures, along with electrophysiological assays and computational studies, provide mechanistic insights into the ligand activation of KCNQ2 and may guide the development of anti-epileptic drugs targeting KCNQ2.

Structure basis for the activation of KCNQ2 by endogenous and exogenous ligands.,Zhao Y, Yang Z, Shi S, Hao H, Li X, Ma D, Su N, Zhao W, Shao J, An Y, Wang K, Liu Y, Zou L, Qi J, Zhang H, Guo J, Du X Cell Rep. 2026 Jan 27;45(1):116771. doi: 10.1016/j.celrep.2025.116771. Epub 2025 , Dec 23. PMID:41442279<ref>PMID:41442279</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9xed" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Du XN]]
[[Category: Guo JT]]
[[Category: Yang ZN]]
[[Category: Zhao YW]]