9IVC

Cryo-EM structure of AbA-bound Aur1-Kei1 complex

This is a non-PDB format compatible entry.

Summary for 9IVC

• Entry DOI: 10.2210/pdb9ivc/pdb
• EMDB information: 60924
• Descriptor: Inositol phosphorylceramide synthase catalytic subunit AUR1, Inositol phosphorylceramide synthase regulatory subunit KEI1, Aureobasidin A (3 entities in total)
• Functional Keywords: inhibitor, complex, transferase
• Biological source: Saccharomyces cerevisiae S288C; More
• Total number of polymer chains: 6
• Total formula weight: 157706.96

Authors

Xie, T.,Wu, X.,Gong, X. (deposition date: 2024-07-23, release date: 2025-06-18)

Primary citation

Wu, X.,Gong, X.,Xie, T.
Mechanisms of aureobasidin A inhibition and drug resistance in a fungal IPC synthase complex.
Nat Commun, 16:5010-5010, 2025

PubMed Abstract: The enzyme inositol phosphorylceramide (IPC) synthase is essential for survival and virulence in fungi, while absent in mammals, thus representing a potential target for antifungal treatments. Aureobasidin A (AbA), a natural cyclic peptide, displays antifungal activity and inhibits IPC synthase, but the precise molecular mechanism remains unclear. Here, we present the cryo-EM structure of the Saccharomyces cerevisiae IPC synthase, composed of catalytic subunit Aur1 and regulatory subunit Kei1, in its AbA-bound state. The complex is resolved as a dimer of Aur1-Kei1 heterodimers, with Aur1 mediating homodimerization. AbA occupies a predominantly hydrophobic pocket in the catalytic core domain of each Aur1 subunit, blocking the entry of both substrates. Mutations conferring AbA resistance cluster near the AbA-binding site, thus interfering with AbA binding. Our study lays a foundation for the development of therapeutic drugs targeting fungal IPC synthase.

PubMed: 40442105
DOI: 10.1038/s41467-025-60423-y

Experimental method

ELECTRON MICROSCOPY (3.17 Å)