8j01: Difference between revisions
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==Human KCNQ2-CaM in complex with CBD and PIP2== | |||
<StructureSection load='8j01' size='340' side='right'caption='[[8j01]], [[Resolution|resolution]] 3.10Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[8j01]] 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=8J01 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8J01 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]] 3.1Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=P0T:cannabidiol'>P0T</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=8j01 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8j01 OCA], [https://pdbe.org/8j01 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8j01 RCSB], [https://www.ebi.ac.uk/pdbsum/8j01 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8j01 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 human voltage-gated potassium channel KCNQ2/KCNQ3 carries the neuronal M-current, which helps to stabilize the membrane potential. KCNQ2 can be activated by analgesics and antiepileptic drugs but their activation mechanisms remain unclear. Here we report cryo-electron microscopy (cryo-EM) structures of human KCNQ2-CaM in complex with three activators, namely the antiepileptic drug cannabidiol (CBD), the lipid phosphatidylinositol 4,5-bisphosphate (PIP(2)), and HN37 (pynegabine), an antiepileptic drug in the clinical trial, in an either closed or open conformation. The activator-bound structures, along with electrophysiology analyses, reveal the binding modes of two CBD, one PIP(2), and two HN37 molecules in each KCNQ2 subunit, and elucidate their activation mechanisms on the KCNQ2 channel. These structures may guide the development of antiepileptic drugs and analgesics that target KCNQ2. | |||
Ligand activation mechanisms of human KCNQ2 channel.,Ma D, Zheng Y, Li X, Zhou X, Yang Z, Zhang Y, Wang L, Zhang W, Fang J, Zhao G, Hou P, Nan F, Yang W, Su N, Gao Z, Guo J Nat Commun. 2023 Oct 19;14(1):6632. doi: 10.1038/s41467-023-42416-x. PMID:37857637<ref>PMID:37857637</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 8j01" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Homo sapiens]] | |||
[[Category: Large Structures]] | |||
[[Category: Guo J]] | |||
[[Category: Li X]] | |||
[[Category: Ma D]] | |||
Latest revision as of 14:44, 13 December 2023
Human KCNQ2-CaM in complex with CBD and PIP2Human KCNQ2-CaM in complex with CBD and PIP2
Structural highlights
FunctionPublication Abstract from PubMedThe human voltage-gated potassium channel KCNQ2/KCNQ3 carries the neuronal M-current, which helps to stabilize the membrane potential. KCNQ2 can be activated by analgesics and antiepileptic drugs but their activation mechanisms remain unclear. Here we report cryo-electron microscopy (cryo-EM) structures of human KCNQ2-CaM in complex with three activators, namely the antiepileptic drug cannabidiol (CBD), the lipid phosphatidylinositol 4,5-bisphosphate (PIP(2)), and HN37 (pynegabine), an antiepileptic drug in the clinical trial, in an either closed or open conformation. The activator-bound structures, along with electrophysiology analyses, reveal the binding modes of two CBD, one PIP(2), and two HN37 molecules in each KCNQ2 subunit, and elucidate their activation mechanisms on the KCNQ2 channel. These structures may guide the development of antiepileptic drugs and analgesics that target KCNQ2. Ligand activation mechanisms of human KCNQ2 channel.,Ma D, Zheng Y, Li X, Zhou X, Yang Z, Zhang Y, Wang L, Zhang W, Fang J, Zhao G, Hou P, Nan F, Yang W, Su N, Gao Z, Guo J Nat Commun. 2023 Oct 19;14(1):6632. doi: 10.1038/s41467-023-42416-x. PMID:37857637[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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