9L3E9L3E の概要
| エントリーDOI | 10.2210/pdb9l3e/pdb |
| 分子名称 | Glyceraldehyde-3-phosphate dehydrogenase, (4~{a}~{S},5~{S},5~{a}~{R},6~{S},8~{a}~{R},9~{S},9~{a}~{S})-3,6,9-trimethyl-5-[(1~{S},2~{R})-2-methyl-4-(3-methylfuran-2-yl)-1-oxidanyl-butyl]-3,4,5~{a},6,7,8,8~{a},9-octahydro-2~{H}-cyclopenta[g]chromene-4~{a},5,9~{a}-triol, ZINC ION, ... (8 entities in total) |
| 機能のキーワード | gapdh, immune system, compound target |
| 由来する生物種 | Homo sapiens (human) 詳細 |
| タンパク質・核酸の鎖数 | 4 |
| 化学式量合計 | 149495.57 |
| 構造登録者 | |
| 主引用文献 | Zhou, T.T.,Zheng, Y.,Zhang, M.W.,Gong, L.H.,Guo, K.,He, X.P.,Liu, Y.C.,Gershenzon, J.,Liu, Y.,Li, S.H. Plant defense-directed discovery of a natural anti-psoriasis agent targeting GAPDH. Sci Adv, 11:eadw2578-eadw2578, 2025 Cited by PubMed Abstract: Elucidating the ecological functions of natural products in plant adaptive mechanisms is an emerging means of discovering lead compounds. Here, we show an undescribed plant glandular trichome-specific defense sesterterpenoid, leucosceptrine F (leu-F), exhibiting potent anti-inflammatory activity by modulating both innate and adaptive immune responses. Leu-F irreversibly binds to glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a cross-kingdom glycolytic enzyme and a promising therapeutic target in autoimmune diseases. Crystal structure of the GAPDH-leu-F complex reveals the formation of a covalent bond between leu-F and the Cys residue. Leu-F notably attenuated glycolysis and concurrently diminished GAPDH-mediated stabilization of activated protein kinase B (AKT). Both leu-F and the total sesterterpenoid extract of demonstrated notable therapeutic efficacy and safety in mouse models of psoriasis and experimental autoimmune encephalomyelitis. This study underscores leu-F as a promising lead compound for autoimmune disease treatment and provides a compelling example of drug discovery inspired by chemical ecology. PubMed: 40712011DOI: 10.1126/sciadv.adw2578 主引用文献が同じPDBエントリー |
| 実験手法 | X-RAY DIFFRACTION (1.77 Å) |
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