9JO3
Cryo-EM structure of human BKca channel-compound 10b complex
This is a non-PDB format compatible entry.
Summary for 9JO3
| Entry DOI | 10.2210/pdb9jo3/pdb |
| EMDB information | 61642 |
| Descriptor | Calcium-activated potassium channel subunit alpha-1, MAGNESIUM ION, CALCIUM ION, ... (6 entities in total) |
| Functional Keywords | bkca channel, compound 10b, cryo-em, membrane protein |
| Biological source | Homo sapiens (human) |
| Total number of polymer chains | 4 |
| Total formula weight | 513887.32 |
| Authors | |
| Primary citation | Park, S.B.,Lee, N.Y.,Lee, E.Y.,Kim, S.,Lee, N.,Roh, E.C.,Kim, Y.G.,Kim, H.J.,Jin, M.S.,Park, C.S.,Kim, Y.C. Discovery of Diphenyl Ether Derivatives as Novel BK Ca Channel Activators: Structure-Activity Relationship, Cryo-EM Complex Structures, and In Vivo Animal Studies. J.Med.Chem., 68:4259-4286, 2025 Cited by PubMed Abstract: The BK channel, a large-conductance calcium-activated potassium channel, plays a crucial role in maintaining the homeostasis of the micturition cycle and airway-related functions. In this study, we optimized a novel BK channel activator, , with a diphenyl ether structure identified from library screening. This led to the discovery of potent activators, (EC = 0.12 μM, cell-based assay) and , an orally bioavailable derivative. Compound demonstrated potent efficacy in a spontaneous hypertensive rat (SHR) of urinary incontinence model, while compound showed dose-dependent cough suppression efficacy with an ED of 11.8 mg/kg in a citric acid-induced cough model. Furthermore, we reported the cryo-electron microscopy (cryo-EM) structures of the BK channel in complex with and at resolutions of 2.8 and 3.4 Å. Based on structural analyses, we determined the binding sites and key interaction residues of , which were validated via mutation studies. PubMed: 39947888DOI: 10.1021/acs.jmedchem.4c02008 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (2.8 Å) |
Structure validation
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