9WZS
Cryo-EM structure of Fks2 in complex with enfumafungin
This is a non-PDB format compatible entry.
Summary for 9WZS
| Entry DOI | 10.2210/pdb9wzs/pdb |
| EMDB information | 66407 |
| Descriptor | 1,3-beta-glucan synthase component GSC2, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ERGOSTEROL, ... (5 entities in total) |
| Functional Keywords | complex, membrane protein |
| Biological source | Saccharomyces cerevisiae S288C |
| Total number of polymer chains | 1 |
| Total formula weight | 223074.71 |
| Authors | |
| Primary citation | You, Z.L.,Sun, L.,Wang, L.X.,Ni, Y.R.,Lyu, R.Q.,Chen, D.D.,Yun, C.H.,Song, T.,Song, Y.,Bai, L. Inhibition mechanism of the fungal beta-1,3-glucan synthases by triterpenoid antifungal drugs. Nat Commun, 2026 Cited by 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 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. PubMed: 41639077DOI: 10.1038/s41467-026-69114-8 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.32 Å) |
Structure validation
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