Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Inhibition mechanism of the fungal β-1,3-glucan synthases by triterpenoid antifungal drugs.
Journal, issue, pages	Nat Commun, Year 2026
Publish date	Feb 4, 2026
Authors	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 Abstract	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.
External links	Nat Commun / PubMed:41639077
Methods	EM (single particle)
Resolution	2.97 - 3.72 Å
Structure data	66359 9wy1 EMDB-66359, PDB-9wy1: Cryo-EM structure of Fks1 in apo state Method: EM (single particle) / Resolution: 3.23 Å 66407 9wzs EMDB-66407, PDB-9wzs: Cryo-EM structure of Fks2 in complex with enfumafungin Method: EM (single particle) / Resolution: 3.32 Å 66408 9wzt EMDB-66408, PDB-9wzt: Cryo-EM structure of Fks2 in apo state Method: EM (single particle) / Resolution: 3.64 Å 66409 9wzu EMDB-66409, PDB-9wzu: Cryo-EM structure of Fks1 in complex with enfumafungin Method: EM (single particle) / Resolution: 2.97 Å 66410 9wzv EMDB-66410, PDB-9wzv: Cryo-EM structure of Fks1 with intact active site Method: EM (single particle) / Resolution: 3.35 Å 66411 9wzx EMDB-66411, PDB-9wzx: Cryo-EM structure of Fks1 in open state Method: EM (single particle) / Resolution: 3.72 Å 66419 9x04 EMDB-66419, PDB-9x04: Cryo-EM structure of Fks2 with intact active site Method: EM (single particle) / Resolution: 3.41 Å
Chemicals	ChemComp-POV: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / phospholipidYM ChemComp-AV0: Lauryl Maltose Neopentyl Glycol ChemComp-ERG: ERGOSTEROL PDB-1e06*: Porcine Odorant Binding Protein Complexed with 5-methyl-2-(1-methylethyl)phenol
Source	Saccharomyces cerevisiae (brewer's yeast) saccharomyces cerevisiae s288c (yeast) saccharomyces cerevisiae (strain atcc 204508 / s288c) (yeast)
Keywords	MEMBRANE PROTEIN / 1 / 3-beta-glucan synthase component FKS1 / Complex / 3-beta-glucan synthase component GSC2 / enfumafungin