6V36
K2P2.1(TREK-1)I110D apo channel structure
Summary for 6V36
| Entry DOI | 10.2210/pdb6v36/pdb |
| Descriptor | Potassium channel subfamily K member 2, CADMIUM ION, N-OCTANE, ... (6 entities in total) |
| Functional Keywords | potassium channel, trek-1, k2p channel, mouse, membrane protein |
| Biological source | Mus musculus (Mouse) |
| Total number of polymer chains | 2 |
| Total formula weight | 69838.86 |
| Authors | Pope, L.,Lolicato, M.,Minor, D.L. (deposition date: 2019-11-25, release date: 2020-02-26, Last modification date: 2024-11-20) |
| Primary citation | Pope, L.,Lolicato, M.,Minor Jr., D.L. Polynuclear Ruthenium Amines Inhibit K2PChannels via a "Finger in the Dam" Mechanism. Cell Chem Biol, 2020 Cited by PubMed Abstract: The trinuclear ruthenium amine ruthenium red (RuR) inhibits diverse ion channels, including K 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 K, K2.1 (TREK-1) I110D, we show that RuR acts by binding an acidic residue pair comprising the "Keystone inhibitor site" under the K CAP domain archway above the channel pore. We further establish that Ru360, a dinuclear ruthenium amine not known to affect Ks, inhibits RuR-sensitive Ks using the same mechanism. Structural knowledge enabled a generalizable design strategy for creating K RuR "super-responders" having nanomolar sensitivity. Together, the data define a "finger in the dam" inhibition mechanism acting at a novel K inhibitor binding site. These findings highlight the polysite nature of K pharmacology and provide a new framework for K inhibitor development. PubMed: 32059793DOI: 10.1016/j.chembiol.2020.01.011 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (3.4 Å) |
Structure validation
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