9MFF の概要
| エントリーDOI | 10.2210/pdb9mff/pdb |
| 関連するPDBエントリー | 6nf4 6nf6 |
| EMDBエントリー | 48227 9360 9361 |
| 分子名称 | Proton channel OTOP1, CHOLESTEROL HEMISUCCINATE, 4-methyl-N-{2-[(2-methylprop-2-en-1-yl)oxy]phenyl}-1H-imidazole-5-carboxamide, ... (4 entities in total) |
| 機能のキーワード | proton channel, ion channel, otop, otopetrin, membrane protein |
| 由来する生物種 | Danio rerio (zebrafish) |
| タンパク質・核酸の鎖数 | 2 |
| 化学式量合計 | 136986.08 |
| 構造登録者 | |
| 主引用文献 | Burendei, B.,Kaplan, J.P.,Orellana, G.M.,Liman, E.R.,Forli, S.,Ward, A.B. Structure-guided discovery of Otopetrin 1 inhibitors reveals druggable binding sites at the intrasubunit interface. Nat Commun, 16:9362-9362, 2025 Cited by PubMed Abstract: Proton conductance across cell membranes serves many biological functions, ranging from the regulation of intracellular and extracellular pH to the generation of electrical signals that lead to sour taste perception. Otopetrins (OTOPs) are a conserved, eukaryotic family of proton-selective ion channels, one of which (OTOP1) serves as a gustatory sensor for sour tastes and ammonium chloride. As the functional properties and structures of OTOP channels were only recently described, there are presently few tools available to modulate their activity. Here, we perform subsequent rounds of molecular docking-based virtual screening against the structure of zebrafish OTOP1, followed by functional testing using whole-cell patch-clamp electrophysiology, and identify several small molecule inhibitors that are effective in the low-to-mid µM range. Cryo-electron microscopy structures reveal inhibitor binding sites in the intrasubunit interface that are validated by functional testing of mutant channels. Our findings reveal pockets that can be targeted for small molecule discovery to develop modulators for Otopetrins. Such modulators can serve as useful toolkit molecules for future investigations of structure-function relationships or physiological roles of Otopetrins. PubMed: 41130946DOI: 10.1038/s41467-025-64392-0 主引用文献が同じPDBエントリー |
| 実験手法 | ELECTRON MICROSCOPY (3.23 Å) |
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