9vj4: Difference between revisions
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==Structure of a membrane-bound inositol phosphorylceramide synthase and ceramide complex== | |||
<StructureSection load='9vj4' size='340' side='right'caption='[[9vj4]], [[Resolution|resolution]] 3.50Å' scene=''> | |||
== Structural highlights == | |||
<table><tr><td colspan='2'>[[9vj4]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae_S288C Saccharomyces cerevisiae S288C]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=9VJ4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9VJ4 FirstGlance]. <br> | |||
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.5Å</td></tr> | |||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=46E:(2R)-3-{[(S)-(2-AMINOETHOXY)(HYDROXY)PHOSPHORYL]OXY}-2-(TETRADECANOYLOXY)PROPYL+TETRADECANOATE'>46E</scene>, <scene name='pdbligand=C14:TETRADECANE'>C14</scene>, <scene name='pdbligand=UJO:~{N}-[(~{Z},2~{S},3~{R})-1,3-bis(oxidanyl)heptadec-4-en-2-yl]dodecanamide'>UJO</scene></td></tr> | |||
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=9vj4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9vj4 OCA], [https://pdbe.org/9vj4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9vj4 RCSB], [https://www.ebi.ac.uk/pdbsum/9vj4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9vj4 ProSAT]</span></td></tr> | |||
</table> | |||
== Function == | |||
[https://www.uniprot.org/uniprot/AUR1_YEAST 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.<ref>PMID:10888667</ref> <ref>PMID:19047657</ref> <ref>PMID:19726565</ref> <ref>PMID:9092515</ref> | |||
<div style="background-color:#fffaf0;"> | |||
== 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<ref>PMID:41708645</ref> | |||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |||
[[Category: | </div> | ||
<div class="pdbe-citations 9vj4" style="background-color:#fffaf0;"></div> | |||
== References == | |||
<references/> | |||
__TOC__ | |||
</StructureSection> | |||
[[Category: Large Structures]] | |||
[[Category: Saccharomyces cerevisiae S288C]] | |||
[[Category: Chen JH]] | |||
[[Category: Ke Y]] | |||
[[Category: Yu HJ]] | |||
[[Category: Zhang M]] | |||
Latest revision as of 09:17, 11 March 2026
Structure of a membrane-bound inositol phosphorylceramide synthase and ceramide complex
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