7cr2: Difference between revisions
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==human KCNQ2 in complex with retigabine== | ==human KCNQ2 in complex with retigabine== | ||
<StructureSection load='7cr2' size='340' side='right'caption='[[7cr2]]' scene=''> | <StructureSection load='7cr2' size='340' side='right'caption='[[7cr2]], [[Resolution|resolution]] 3.20Å' scene=''> | ||
== Structural highlights == | == 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 [http://proteopedia.org/fgij/fg.htm?mol=7CR2 FirstGlance]. <br> | <table><tr><td colspan='2'>[[7cr2]] is a 4 chain structure with sequence from [http://en.wikipedia.org/wiki/Human Human]. 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 [http://proteopedia.org/fgij/fg.htm?mol=7CR2 FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7cr2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cr2 OCA], [http://pdbe.org/7cr2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7cr2 RCSB], [http://www.ebi.ac.uk/pdbsum/7cr2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7cr2 ProSAT]</span></td></tr> | </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='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[7cr0|7cr0]], [[7cr1|7cr1]]</td></tr> | |||
<tr id='gene'><td class="sblockLbl"><b>[[Gene|Gene:]]</b></td><td class="sblockDat">KCNQ2 ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=9606 HUMAN])</td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://proteopedia.org/fgij/fg.htm?mol=7cr2 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cr2 OCA], [http://pdbe.org/7cr2 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=7cr2 RCSB], [http://www.ebi.ac.uk/pdbsum/7cr2 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=7cr2 ProSAT]</span></td></tr> | |||
</table> | </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. | |||
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> | |||
</div> | |||
<div class="pdbe-citations 7cr2" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Guo J]] | [[Category: Guo, J]] | ||
[[Category: Li X]] | [[Category: Li, X]] | ||
[[Category: Lv D]] | [[Category: Lv, D]] | ||
[[Category: Wang J]] | [[Category: Wang, J]] | ||
[[Category: Ye S]] | [[Category: Ye, S]] | ||
[[Category: Ion channel]] | |||
[[Category: Transport protein]] | |||