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| Title | Cryo-EM structures of Candida albicans chitin synthase Chs1 reveal a druggable translocation channel. |
|---|---|
| Journal, issue, pages | Nat Microbiol, Year 2026 |
| Publish date | Sep 15, 2026 |
Authors | Zhenning Ren / Abhishek Chhetri / Chang Liu / Ziqiang Guan / ShuYu Offner / Dmitry Kozhanov / Mario J Borgnia / Wonpil Im / Kenichi Yokoyama / Seok-Yong Lee / ![]() |
| PubMed Abstract | Invasive candidiasis is a leading cause of hospital-acquired bloodstream infections with high mortality. While the fungal cell wall is an excellent therapeutic target, inhibitor development against ...Invasive candidiasis is a leading cause of hospital-acquired bloodstream infections with high mortality. While the fungal cell wall is an excellent therapeutic target, inhibitor development against the essential chitin synthase (Chs) has been hampered by the absence of structural and mechanistic understanding of class II Chs, which contribute to fungal viability. Here we present cryo-electron microscopy structures of Candida albicans class II Chs (CaChs1) at 2.93-3.38 Å resolution, providing insights into its mechanisms of early elongation, chito-oligomer translocation and inhibition by the CaChs1-specific non-competitive inhibitor diynyl arylamine (DA). Chitin elongation and translocation are coupled to coordinated motion of the glycosyltransferase domain and the dimer interface. Notably, DA binds within the chitin translocation channel where a regulatory lipid resides and inhibits the enzyme by occluding product polymer extrusion. Importantly, DA showed potent synergy with the class I Chs inhibitor nikkomycin Z against C. albicans and Candida auris. These findings establish the chitin translocation channel as a druggable site for rational antifungal design. |
External links | Nat Microbiol / PubMed:42744982 / PubMed Central |
| Methods | EM (single particle) |
| Resolution | 2.85 - 3.38 Å |
| Structure data | EMDB-76826, PDB-12xf: EMDB-76827, PDB-12xg: EMDB-76828, PDB-12xh: EMDB-76829, PDB-12xi: EMDB-76830, PDB-12xj: EMDB-76831, PDB-12xk: EMDB-76832, PDB-12xl: EMDB-76833, PDB-12xm: EMDB-76834, PDB-12xn: EMDB-76835, PDB-12xo: EMDB-76836, PDB-12xp: EMDB-76837, PDB-12xq: |
| Chemicals | ![]() ChemComp-PEE: ![]() ChemComp-MG: ![]() ChemComp-NAG: ![]() ChemComp-UDP: ![]() ChemComp-HOH: ![]() PDB-1deh: ![]() ChemComp-UD1: |
| Source |
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Keywords | MEMBRANE PROTEIN / Enzyme / chitin synthesis |
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candida albicans (yeast)
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