9vj4 | pdb_00009vj4

Structure of a membrane-bound inositol phosphorylceramide synthase and ceramide complex

spinqualitylabelsall models 9vj4, resolution 3.50Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9vj4 is a 2 chain structure with sequence from Saccharomyces cerevisiae S288C. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.5Å Ligands: 46E, C14, UJO Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function AUR1_YEAST Catalytic component of the inositol phosphorylceramide synthase which catalyzes the addition of a phosphorylinositol group onto ceramide to form inositol phosphorylceramide, an essential step in sphingolipid biosynthesis. Publication Abstract from PubMed 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. Molecular insights into fungal inositol phosphorylceramide synthesis and its inhibition by antifungal aureobasidin A.,Chen J, Ke Y, Zhang M, Lin X, Hua Z, Zhang D, Hu X, Ding X, Li J, Yang P, Yu H Nat Commun. 2026 Feb 19. doi: 10.1038/s41467-026-69777-3. PMID:41708645 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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