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- EMDB-65103: Structure of a membrane-bound inositol phosphorylceramide synthas... -

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Basic information

Entry
Database: EMDB / ID: EMD-65103
TitleStructure of a membrane-bound inositol phosphorylceramide synthase and ceramide complex
Map data
Sample
  • Complex: membrane-bound inositol phosphorylceramide synthase and ceramide complex
    • Protein or peptide: Inositol phosphorylceramide synthase catalytic subunit AUR1
    • Protein or peptide: Inositol phosphorylceramide synthase regulatory subunit KEI1
  • Ligand: ~{N}-[(~{Z},2~{S},3~{R})-1,3-bis(oxidanyl)heptadec-4-en-2-yl]dodecanamide
  • Ligand: TETRADECANE
  • Ligand: (2R)-3-{[(S)-(2-aminoethoxy)(hydroxy)phosphoryl]oxy}-2-(tetradecanoyloxy)propyl tetradecanoate
Keywordsmembrane protein / inositol phosphorylceramide synthase / LIPID BINDING PROTEIN
Function / homology
Function and homology information


inositol phosphorylceramide synthase / mannosyl diphosphorylinositol ceramide metabolic process / inositol phosphoceramide synthase activity / inositol phosphoceramide synthase complex / inositol phosphoceramide synthase regulator activity / inositol phosphoceramide metabolic process / sphingolipid biosynthetic process / Golgi cisterna membrane / Golgi membrane / endoplasmic reticulum ...inositol phosphorylceramide synthase / mannosyl diphosphorylinositol ceramide metabolic process / inositol phosphoceramide synthase activity / inositol phosphoceramide synthase complex / inositol phosphoceramide synthase regulator activity / inositol phosphoceramide metabolic process / sphingolipid biosynthetic process / Golgi cisterna membrane / Golgi membrane / endoplasmic reticulum / Golgi apparatus / cytoplasm
Similarity search - Function
Inositolphosphorylceramide synthase subunit Kei1 / Inositolphosphotransferase Aur1/Ipt1 / : / Inositolphosphorylceramide synthase subunit Kei1 / PAP2 superfamily / Acid phosphatase homologues / Phosphatidic acid phosphatase type 2/haloperoxidase / Phosphatidic acid phosphatase type 2/haloperoxidase superfamily
Similarity search - Domain/homology
Inositol phosphorylceramide synthase catalytic subunit AUR1 / Inositol phosphorylceramide synthase regulatory subunit KEI1
Similarity search - Component
Biological speciesSaccharomyces cerevisiae (brewer's yeast) / Saccharomyces cerevisiae S288C (yeast)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.5 Å
AuthorsChen JH / Ke Y / Zhang M / Yu HJ
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC) China
CitationJournal: Nat Commun / Year: 2026
Title: Molecular insights into fungal inositol phosphorylceramide synthesis and its inhibition by antifungal aureobasidin A.
Authors: Jiehui Chen / Yan Ke / Min Zhang / Xinyuan Lin / Zhengkang Hua / Di Zhang / Xinlin Hu / Xuyang Ding / Jiameng Li / Ping Yang / Hongjun Yu /
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 ...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.
History
DepositionJun 19, 2025-
Header (metadata) releaseMar 11, 2026-
Map releaseMar 11, 2026-
UpdateMar 11, 2026-
Current statusMar 11, 2026Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_65103.png

Downloads & links

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Map

FileDownload / File: emd_65103.map.gz / Format: CCP4 / Size: 34.3 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.93 Å/pix.
x 208 pix.
= 192.608 Å		0.93 Å/pix.
x 208 pix.
= 192.608 Å		0.93 Å/pix.
x 208 pix.
= 192.608 Å

Surface

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Images are generated by Spider.

Voxel sizeX=Y=Z: 0.926 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.4
Minimum - Maximum-1.958966 - 2.9450421
Average (Standard dev.)0.0015761871 (±0.063511506)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions208208208
Spacing208208208
CellA=B=C: 192.608 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_65103_half_map_1.map
Projections & Slices
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Histogram

Histogram (log scale)

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Half map: #1

Fileemd_65103_half_map_2.map
Projections & Slices
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Sample components

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Entire : membrane-bound inositol phosphorylceramide synthase and ceramide ...

EntireName: membrane-bound inositol phosphorylceramide synthase and ceramide complex
Components
  • Complex: membrane-bound inositol phosphorylceramide synthase and ceramide complex
    • Protein or peptide: Inositol phosphorylceramide synthase catalytic subunit AUR1
    • Protein or peptide: Inositol phosphorylceramide synthase regulatory subunit KEI1
  • Ligand: ~{N}-[(~{Z},2~{S},3~{R})-1,3-bis(oxidanyl)heptadec-4-en-2-yl]dodecanamide
  • Ligand: TETRADECANE
  • Ligand: (2R)-3-{[(S)-(2-aminoethoxy)(hydroxy)phosphoryl]oxy}-2-(tetradecanoyloxy)propyl tetradecanoate

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Supramolecule #1: membrane-bound inositol phosphorylceramide synthase and ceramide ...

SupramoleculeName: membrane-bound inositol phosphorylceramide synthase and ceramide complex
type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1-#2
Source (natural)Organism: Saccharomyces cerevisiae (brewer's yeast)
Molecular weightTheoretical: 71 KDa

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Macromolecule #1: Inositol phosphorylceramide synthase catalytic subunit AUR1

MacromoleculeName: Inositol phosphorylceramide synthase catalytic subunit AUR1
type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: inositol phosphorylceramide synthase
Source (natural)Organism: Saccharomyces cerevisiae S288C (yeast)
Molecular weightTheoretical: 45.223023 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MANPFSRWFL SERPPNCHVA DLETSLDPHQ TLLKVQKYKP ALSDWVHYIF LGSIMLFVFI TNPAPWIFKI LFYCFLGTLF IIPATSQFF FNALPILTWV ALYFTSSYFP DDRRPPITVK VLPAVETILY GDNLSDILAT STNSFLDILA WLPYGLFHFG A PFVVAAIL ...String:
MANPFSRWFL SERPPNCHVA DLETSLDPHQ TLLKVQKYKP ALSDWVHYIF LGSIMLFVFI TNPAPWIFKI LFYCFLGTLF IIPATSQFF FNALPILTWV ALYFTSSYFP DDRRPPITVK VLPAVETILY GDNLSDILAT STNSFLDILA WLPYGLFHFG A PFVVAAIL FVFGPPTVLQ GYAFAFGYMN LFGVIMQNVF PAAPPWYKIL YGLQSANYDM HGSPGGLARI DKLLGINMYT TA FSNSSVI FGAFPSLHSG CATMEALFFC YCFPKLKPLF IAYVCWLWWS TMYLTHHYFV DLMAGSVLSY VIFQYTKYTH LPI VDTSLF CRWSYTSIEK YDISKSDPLA ADSNDIESVP LSNLELDFDL NMTDEPSVSP SLFDGSTSVS RSSATSITSL GVKR A

UniProtKB: Inositol phosphorylceramide synthase catalytic subunit AUR1

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Macromolecule #2: Inositol phosphorylceramide synthase regulatory subunit KEI1

MacromoleculeName: Inositol phosphorylceramide synthase regulatory subunit KEI1
type: protein_or_peptide / ID: 2 / Number of copies: 1 / Enantiomer: LEVO
Source (natural)Organism: Saccharomyces cerevisiae S288C (yeast)
Molecular weightTheoretical: 25.505799 KDa
Recombinant expressionOrganism: Homo sapiens (human)
SequenceString: MRSSLLTLPK SFLGFMPLYL AVEIVLGISI LNKCSGAYGI LALFTGHPLD FMQWIAYLWS VFTLIVFSQG LYLIHKPNLL VFSQICVLY TIDTISTCFF TLWFTTQWFT LEDTANIDGN NALQSNPIST GKLTERGIDI SKQSATESYE YTMTILITLV S LIFRFYFN ...String:
MRSSLLTLPK SFLGFMPLYL AVEIVLGISI LNKCSGAYGI LALFTGHPLD FMQWIAYLWS VFTLIVFSQG LYLIHKPNLL VFSQICVLY TIDTISTCFF TLWFTTQWFT LEDTANIDGN NALQSNPIST GKLTERGIDI SKQSATESYE YTMTILITLV S LIFRFYFN FILASFVQEL LHHPKYLVDR DDVEQNLKNK PIWKRLWAKS QKGCYKLCKN LLE

UniProtKB: Inositol phosphorylceramide synthase regulatory subunit KEI1

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Macromolecule #3: ~{N}-[(~{Z},2~{S},3~{R})-1,3-bis(oxidanyl)heptadec-4-en-2-yl]dode...

MacromoleculeName: ~{N}-[(~{Z},2~{S},3~{R})-1,3-bis(oxidanyl)heptadec-4-en-2-yl]dodecanamide
type: ligand / ID: 3 / Number of copies: 1 / Formula: UJO
Molecular weightTheoretical: 467.768 Da

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Macromolecule #4: TETRADECANE

MacromoleculeName: TETRADECANE / type: ligand / ID: 4 / Number of copies: 2 / Formula: C14
Molecular weightTheoretical: 198.388 Da
Chemical component information

ChemComp-C14:
TETRADECANE

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Macromolecule #5: (2R)-3-{[(S)-(2-aminoethoxy)(hydroxy)phosphoryl]oxy}-2-(tetradeca...

MacromoleculeName: (2R)-3-{[(S)-(2-aminoethoxy)(hydroxy)phosphoryl]oxy}-2-(tetradecanoyloxy)propyl tetradecanoate
type: ligand / ID: 5 / Number of copies: 1 / Formula: 46E
Molecular weightTheoretical: 635.853 Da
Chemical component information

ChemComp-46E:
(2R)-3-{[(S)-(2-aminoethoxy)(hydroxy)phosphoryl]oxy}-2-(tetradecanoyloxy)propyl tetradecanoate

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Experimental details

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Structure determination

Methodcryo EM
Processingsingle particle reconstruction
Aggregation stateparticle

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Sample preparation

BufferpH: 7.5
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeTFS TALOS
Image recordingFilm or detector model: GATAN K3 (6k x 4k) / Average electron dose: 50.0 e/Å2
Electron beamAcceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 3.0 µm / Nominal defocus min: 1.1 µm

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: INSILICO MODEL
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.5 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC / Number images used: 162123
Initial angle assignmentType: MAXIMUM LIKELIHOOD
Final angle assignmentType: MAXIMUM LIKELIHOOD
FSC plot (resolution estimation)

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