EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Inhibition mechanism of the fungal β-1,3-glucan synthases by triterpenoid antifungal drugs.
ジャーナル・号・ページ	Nat Commun, Vol. 17, Issue 1, Year 2026
掲載日	2026年2月4日
著者	Zi-Long You / Lei Sun / Le-Xuan Wang / Yue-Ran Ni / Rui-Qing Lyu / Dan-Dan Chen / Cai-Hong Yun / Tiefeng Song / Yinggai Song / Lin Bai /
PubMed 要旨	β-1,3-glucan synthase is the molecular target for triterpenoid and echinocandin antifungal drugs in clinical. It catalyzes the formation of β-1,3-glucan, which is the primary component of the ...β-1,3-glucan synthase is the molecular target for triterpenoid and echinocandin antifungal drugs in clinical. It catalyzes the formation of β-1,3-glucan, which is the primary component of the fungal cell wall. However, the inhibition mechanism of β-1,3-glucan synthase by triterpenoid drugs remains unclear. In this study, we report cryo-electron microscopy (cryo-EM) structures of Saccharomyces cerevisiae β-1,3-glucan synthase Fks1 and Fks2 in the apo state, the triterpenoid drug enfumafungin-bound state, and an open state. Structural analysis along with mutagenesis reveals the enfumafungin binding site, and the mechanism of the clinical drug-resistant mutations of the β-1,3-glucan synthases. Remarkably, the enfumafungin attaches on a single transmembrane helix TM5 of the β-1,3-glucan synthases, reorganizes its nearby lipid environment, and stabilizes the enzyme in a specific basal state with intact active site. Moreover, we elucidate that both the basal state and the open state are essential for FKS's glycosyltransferase activity. Our research also shows that Fks2 is highly conserved with Fks1 in terms of structure, activity, and drug inhibition. These findings provide deep insights into the fungal cell wall synthesis, and will facilitate the development of antifungal drugs targeting β-1,3-glucan synthase.
リンク	Nat Commun / PubMed:41639077 / PubMed Central
手法	EM (単粒子)
解像度	2.97 - 3.72 Å
構造データ	66359 9wy1 EMDB-66359, PDB-9wy1: Cryo-EM structure of Fks1 in apo state 手法: EM (単粒子) / 解像度: 3.23 Å 66407 9wzs EMDB-66407, PDB-9wzs: Cryo-EM structure of Fks2 in complex with enfumafungin 手法: EM (単粒子) / 解像度: 3.32 Å 66408 9wzt EMDB-66408, PDB-9wzt: Cryo-EM structure of Fks2 in apo state 手法: EM (単粒子) / 解像度: 3.64 Å 66409 9wzu EMDB-66409, PDB-9wzu: Cryo-EM structure of Fks1 in complex with enfumafungin 手法: EM (単粒子) / 解像度: 2.97 Å 66410 9wzv EMDB-66410, PDB-9wzv: Cryo-EM structure of Fks1 with intact active site 手法: EM (単粒子) / 解像度: 3.35 Å 66411 9wzx EMDB-66411, PDB-9wzx: Cryo-EM structure of Fks1 in open state 手法: EM (単粒子) / 解像度: 3.72 Å 66419 9x04 EMDB-66419, PDB-9x04: Cryo-EM structure of Fks2 with intact active site 手法: EM (単粒子) / 解像度: 3.41 Å
化合物	ChemComp-POV: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / リン脂質YM ChemComp-AV0: Lauryl Maltose Neopentyl Glycol ChemComp-ERG: ERGOSTEROL PDB-1e06*: Porcine Odorant Binding Protein Complexed with 5-methyl-2-(1-methylethyl)phenol
由来	Saccharomyces cerevisiae (パン酵母) saccharomyces cerevisiae s288c (パン酵母) saccharomyces cerevisiae (strain atcc 204508 / s288c) (パン酵母)
キーワード	MEMBRANE PROTEIN / 1 / 3-beta-glucan synthase component FKS1 / Complex / 3-beta-glucan synthase component GSC2 / enfumafungin