12XM

Candida albicans Chitin synthase 1 (CaChs1) intermediate state (DA-3), bound to UDP and diynyl arylamine (DA, aka RO-09-3143)

This is a non-PDB format compatible entry.

Summary for 12XM

• Entry DOI: 10.2210/pdb12xm/pdb
• EMDB information: 76833
• Descriptor: Chitin synthase, 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine, MAGNESIUM ION, ... (5 entities in total)
• Functional Keywords: enzyme, chitin synthesis, membrane protein
• Biological source: Candida albicans
• Total number of polymer chains: 2
• Total formula weight: 244545.58

Authors

Ren, Z.,Lee, S.Y. (deposition date: 2026-04-21, release date: 2026-10-14)

Primary citation

Ren, Z.,Chhetri, A.,Liu, C.,Guan, Z.,Offner, S.,Kozhanov, D.,Borgnia, M.J.,Im, W.,Yokoyama, K.,Lee, S.Y.
Cryo-EM structures of Candida albicans chitin synthase Chs1 reveal a druggable translocation channel.
Nat Microbiol, 2026

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 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.

PubMed: 42744982
DOI: 10.1038/s41564-026-02485-2

Experimental method

ELECTRON MICROSCOPY (3 Å)