7cr2: Difference between revisions

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'''Unreleased structure'''


The entry 7cr2 is ON HOLD
==human KCNQ2 in complex with retigabine==
<StructureSection load='7cr2' size='340' side='right'caption='[[7cr2]], [[Resolution|resolution]] 3.20&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CR2 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CR2 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]] 3.2&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=FBX:ethyl+N-[2-azanyl-4-[(4-fluorophenyl)methylamino]phenyl]carbamate'>FBX</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=7cr2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cr2 OCA], [https://pdbe.org/7cr2 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cr2 RCSB], [https://www.ebi.ac.uk/pdbsum/7cr2 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cr2 ProSAT]</span></td></tr>
</table>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
The voltage-gated potassium channel KCNQ2 is responsible for M-current in neurons and is an important drug target to treat epilepsy, pain and several other diseases related to neuronal hyper-excitability. A list of synthetic compounds have been developed to directly activate KCNQ2, yet our knowledge of their activation mechanism is limited, due to lack of high-resolution structures. Here, we report cryo-electron microscopy (cryo-EM) structures of the human KCNQ2 determined in apo state and in complex with two activators, ztz240 or retigabine, which activate KCNQ2 through different mechanisms. The activator-bound structures, along with electrophysiology analysis, reveal that ztz240 binds at the voltage-sensing domain and directly stabilizes it at the activated state, whereas retigabine binds at the pore domain and activates the channel by an allosteric modulation. By accurately defining ligand-binding sites, these KCNQ2 structures not only reveal different ligand recognition and activation mechanisms, but also provide a structural basis for drug optimization and design.


Authors:  
Molecular basis for ligand activation of the human KCNQ2 channel.,Li X, Zhang Q, Guo P, Fu J, Mei L, Lv D, Wang J, Lai D, Ye S, Yang H, Guo J Cell Res. 2020 Sep 3. pii: 10.1038/s41422-020-00410-8. doi:, 10.1038/s41422-020-00410-8. PMID:32884139<ref>PMID:32884139</ref>


Description:  
From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
[[Category: Unreleased Structures]]
</div>
<div class="pdbe-citations 7cr2" style="background-color:#fffaf0;"></div>
 
==See Also==
*[[Potassium channel 3D structures|Potassium channel 3D structures]]
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Guo J]]
[[Category: Li X]]
[[Category: Lv D]]
[[Category: Wang J]]
[[Category: Ye S]]
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