7cr7: Difference between revisions
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==human KCNQ2-CaM in complex with retigabine== | |||
<StructureSection load='7cr7' size='340' side='right'caption='[[7cr7]], [[Resolution|resolution]] 3.70Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[7cr7]] 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=7CR7 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CR7 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]] 3.7Å</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=7cr7 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cr7 OCA], [https://pdbe.org/7cr7 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cr7 RCSB], [https://www.ebi.ac.uk/pdbsum/7cr7 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cr7 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 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. | |||
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> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 7cr7" style="background-color:#fffaf0;"></div> | |||
==See Also== | |||
*[[Calmodulin 3D structures|Calmodulin 3D structures]] | |||
*[[Potassium channel 3D structures|Potassium channel 3D structures]] | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Guo J]] | |||
[[Category: Li X]] | |||
[[Category: Lv D]] | |||
[[Category: Wang J]] | |||
[[Category: Ye S]] | |||
Latest revision as of 06:32, 25 June 2025
human KCNQ2-CaM in complex with retigabine
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