7cn1: Difference between revisions
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==Cryo-EM structure of K+-bound hERG channel in the presence of astemizole== | ==Cryo-EM structure of K+-bound hERG channel in the presence of astemizole== | ||
<StructureSection load='7cn1' size='340' side='right'caption='[[7cn1]]' scene=''> | <StructureSection load='7cn1' size='340' side='right'caption='[[7cn1]], [[Resolution|resolution]] 3.70Å' 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=7CN1 OCA]. For a <b>guided tour on the structure components</b> use [ | <table><tr><td colspan='2'>[[7cn1]] is a 4 chain structure with sequence from [https://en.wikipedia.org/wiki/Human Human]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7CN1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7CN1 FirstGlance]. <br> | ||
</td></tr><tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[ | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=K:POTASSIUM+ION'>K</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=7cn1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7cn1 OCA], [https://pdbe.org/7cn1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7cn1 RCSB], [https://www.ebi.ac.uk/pdbsum/7cn1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7cn1 ProSAT]</span></td></tr> | |||
</table> | </table> | ||
<div style="background-color:#fffaf0;"> | |||
== Publication Abstract from PubMed == | |||
The hERG channel is a voltage-gated potassium channel involved in cardiac repolarization. Off-target hERG inhibition by drugs has become a critical issue in the pharmaceutical industry. The three-dimensional structure of the hERG channel was recently reported at 3.8-A resolution using cryogenic electron microscopy (cryo-EM). However, the drug inhibition mechanism remains unclear because of the scarce structural information regarding the drug- and potassium-bound hERG channels. In this study, we obtained the cryo-EM density map of potassium-bound hERG channel complexed with astemizole, a well-known hERG inhibitor that increases risk of potentially fatal arrhythmia, at 3.5-A resolution. The structure suggested that astemizole inhibits potassium conduction by binding directly below the selectivity filter. Furthermore, we propose a possible binding model of astemizole to the hERG channel and provide insights into the unusual sensitivity of hERG to several drugs. | |||
Cryo-EM Structure of K(+)-Bound hERG Channel Complexed with the Blocker Astemizole.,Asai T, Adachi N, Moriya T, Oki H, Maru T, Kawasaki M, Suzuki K, Chen S, Ishii R, Yonemori K, Igaki S, Yasuda S, Ogasawara S, Senda T, Murata T Structure. 2021 Mar 4;29(3):203-212.e4. doi: 10.1016/j.str.2020.12.007. Epub 2021, Jan 14. PMID:33450182<ref>PMID:33450182</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
</div> | |||
<div class="pdbe-citations 7cn1" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: Human]] | |||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Adachi N]] | [[Category: Adachi, N]] | ||
[[Category: Asai T]] | [[Category: Asai, T]] | ||
[[Category: Kawasaki M]] | [[Category: Kawasaki, M]] | ||
[[Category: Moriya T]] | [[Category: Moriya, T]] | ||
[[Category: Murata T]] | [[Category: Murata, T]] | ||
[[Category: Senda T]] | [[Category: Senda, T]] | ||
[[Category: Suzuki K]] | [[Category: Suzuki, K]] | ||
[[Category: Potassium channel]] | |||
[[Category: Transport protein]] | |||
Revision as of 09:59, 17 March 2021
Cryo-EM structure of K+-bound hERG channel in the presence of astemizoleCryo-EM structure of K+-bound hERG channel in the presence of astemizole
Structural highlights
Publication Abstract from PubMedThe hERG channel is a voltage-gated potassium channel involved in cardiac repolarization. Off-target hERG inhibition by drugs has become a critical issue in the pharmaceutical industry. The three-dimensional structure of the hERG channel was recently reported at 3.8-A resolution using cryogenic electron microscopy (cryo-EM). However, the drug inhibition mechanism remains unclear because of the scarce structural information regarding the drug- and potassium-bound hERG channels. In this study, we obtained the cryo-EM density map of potassium-bound hERG channel complexed with astemizole, a well-known hERG inhibitor that increases risk of potentially fatal arrhythmia, at 3.5-A resolution. The structure suggested that astemizole inhibits potassium conduction by binding directly below the selectivity filter. Furthermore, we propose a possible binding model of astemizole to the hERG channel and provide insights into the unusual sensitivity of hERG to several drugs. Cryo-EM Structure of K(+)-Bound hERG Channel Complexed with the Blocker Astemizole.,Asai T, Adachi N, Moriya T, Oki H, Maru T, Kawasaki M, Suzuki K, Chen S, Ishii R, Yonemori K, Igaki S, Yasuda S, Ogasawara S, Senda T, Murata T Structure. 2021 Mar 4;29(3):203-212.e4. doi: 10.1016/j.str.2020.12.007. Epub 2021, Jan 14. PMID:33450182[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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