6v36
From Proteopedia
(Difference between revisions)
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| - | '''Unreleased structure''' | ||
| - | + | ==K2P2.1(TREK-1)I110D apo channel structure== | |
| + | <StructureSection load='6v36' size='340' side='right'caption='[[6v36]], [[Resolution|resolution]] 3.40Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[6v36]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=6V36 OCA]. For a <b>guided tour on the structure components</b> use [http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6V36 FirstGlance]. <br> | ||
| + | </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CD:CADMIUM+ION'>CD</scene>, <scene name='pdbligand=K:POTASSIUM+ION'>K</scene>, <scene name='pdbligand=OCT:N-OCTANE'>OCT</scene>, <scene name='pdbligand=UND:UNDECANE'>UND</scene></td></tr> | ||
| + | <tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=6v36 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=6v36 OCA], [http://pdbe.org/6v36 PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=6v36 RCSB], [http://www.ebi.ac.uk/pdbsum/6v36 PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=6v36 ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | The trinuclear ruthenium amine ruthenium red (RuR) inhibits diverse ion channels, including K2P potassium channels, TRPs, the calcium uniporter, CALHMs, ryanodine receptors, and Piezos. Despite this extraordinary array, there is limited information for how RuR engages targets. Here, using X-ray crystallographic and electrophysiological studies of an RuR-sensitive K2P, K2P2.1 (TREK-1) I110D, we show that RuR acts by binding an acidic residue pair comprising the "Keystone inhibitor site" under the K2P CAP domain archway above the channel pore. We further establish that Ru360, a dinuclear ruthenium amine not known to affect K2Ps, inhibits RuR-sensitive K2Ps using the same mechanism. Structural knowledge enabled a generalizable design strategy for creating K2P RuR "super-responders" having nanomolar sensitivity. Together, the data define a "finger in the dam" inhibition mechanism acting at a novel K2P inhibitor binding site. These findings highlight the polysite nature of K2P pharmacology and provide a new framework for K2P inhibitor development. | ||
| - | + | Polynuclear Ruthenium Amines Inhibit K2P Channels via a "Finger in the Dam" Mechanism.,Pope L, Lolicato M, Minor DL Jr Cell Chem Biol. 2020 Feb 10. pii: S2451-9456(20)30036-2. doi:, 10.1016/j.chembiol.2020.01.011. PMID:32059793<ref>PMID:32059793</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 6v36" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Lolicato, M]] | ||
| + | [[Category: Minor, D L]] | ||
| + | [[Category: Pope, L]] | ||
| + | [[Category: K2p channel]] | ||
| + | [[Category: Membrane protein]] | ||
| + | [[Category: Mouse]] | ||
| + | [[Category: Potassium channel]] | ||
| + | [[Category: Trek-1]] | ||
Revision as of 09:26, 26 February 2020
K2P2.1(TREK-1)I110D apo channel structure
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