9XD0
Structure of a membrane-bound inositol phosphorylceramide synthase and Aureobasidin A complex
This is a non-PDB format compatible entry.
Summary for 9XD0
| Entry DOI | 10.2210/pdb9xd0/pdb |
| EMDB information | 66750 |
| Descriptor | Inositol phosphorylceramide synthase catalytic subunit AUR1, Inositol phosphorylceramide synthase regulatory subunit KEI1, Aureobasidin-A, ... (5 entities in total) |
| Functional Keywords | membrane protein, inositol phosphorylceramide synthase, lipid binding protein, transferase |
| Biological source | Saccharomyces cerevisiae S288C More |
| Total number of polymer chains | 3 |
| Total formula weight | 72880.89 |
| Authors | |
| Primary citation | Chen, J.,Ke, Y.,Zhang, M.,Lin, X.,Hua, Z.,Zhang, D.,Hu, X.,Ding, X.,Li, J.,Yang, P.,Yu, H. Molecular insights into fungal inositol phosphorylceramide synthesis and its inhibition by antifungal aureobasidin A. Nat Commun, 2026 Cited by PubMed Abstract: Fungal inositol phosphorylceramide (IPC) synthase is an essential enzyme complex that catalyzes a critical step in sphingolipid biosynthesis. It is the molecular target of potent antifungal aureobasidin A (AbA). Despite its therapeutic relevance, the lack of structural and mechanistic insights into IPC synthase function and inhibition has impeded rational antifungal drug development. Here, we present cryo-EM structures of Saccharomyces cerevisiae IPC synthase in two distinct functional states: a ceramide-bound form and an AbA-inhibited complex. Our study reveals a conserved heterodimeric architecture formed by Aur1 and Kei1, stabilized through extensive protein-protein and lipid-mediated interactions. Within catalytic Aur1, we identify a membrane-embedded reaction chamber harboring a conserved H-H-D catalytic triad (H255, H294, and D298) essential for IPC synthesis. Structural comparisons illuminate the mechanism of ceramide recognition and reveal how AbA acts as a competitive inhibitor by occupying the substrate-binding pocket. Further analyses identify key residues involved in AbA binding and explain the molecular basis of drug resistance. Together, these findings advance the mechanistic understanding of fungal IPC biosynthesis and inhibition, and establish a foundation for developing new antifungal drugs targeting IPC synthase. PubMed: 41708645DOI: 10.1038/s41467-026-69777-3 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.53 Å) |
Structure validation
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