View source for 8izd


==Cryo-EM structure of the C26-CoA-bound Lac1-Lip1 complex==
<StructureSection load='8izd' size='340' side='right'caption='[[8izd]], [[Resolution|resolution]] 3.09&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[8izd]] is a 4 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=8IZD OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8IZD 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]] 3.09&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=6PL:(4S,7R)-4-HYDROXY-N,N,N-TRIMETHYL-9-OXO-7-[(PALMITOYLOXY)METHYL]-3,5,8-TRIOXA-4-PHOSPHAHEXACOSAN-1-AMINIUM+4-OXIDE'>6PL</scene>, <scene name='pdbligand=9NY:~{S}-[2-[3-[[(2~{R})-4-[[[(2~{R},3~{S},4~{R},5~{R})-5-(6-aminopurin-9-yl)-4-oxidanyl-3-phosphonooxy-oxolan-2-yl]methoxy-oxidanyl-phosphoryl]oxy-oxidanyl-phosphoryl]oxy-3,3-dimethyl-2-oxidanyl-butanoyl]amino]propanoylamino]ethyl]+hexacosanethioate'>9NY</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=8izd FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8izd OCA], [https://pdbe.org/8izd PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8izd RCSB], [https://www.ebi.ac.uk/pdbsum/8izd PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8izd ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/LAC1_YEAST LAC1_YEAST] Component of the ceramide synthase complex that catalyzes the transfer of the acyl chain from acyl-CoA to a sphingoid base, with high selectivity toward hexacosanoyl-CoA (C26:0-CoA) (PubMed:11694577, PubMed:15692566). N-acylates sphinganine and phytosphingosine bases to form dihydroceramides and phytoceramides, respectively (PubMed:11694577, PubMed:15692566). Redundant with LAG1. Facilitates ER-to-Golgi transport of GPI-anchored proteins.<ref>PMID:10198056</ref> <ref>PMID:11387200</ref> <ref>PMID:11694577</ref> <ref>PMID:15692566</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
Ceramide synthases (CerS) catalyze ceramide formation via N-acylation of a sphingoid base with a fatty acyl-CoA and are attractive drug targets for treating numerous metabolic diseases and cancers. Here, we present the cryo-EM structure of a yeast CerS complex, consisting of a catalytic Lac1 subunit and a regulatory Lip1 subunit, in complex with C26-CoA substrate. The CerS holoenzyme exists as a dimer of Lac1-Lip1 heterodimers. Lac1 contains a hydrophilic reaction chamber and a hydrophobic tunnel for binding the CoA moiety and C26-acyl chain of C26-CoA, respectively. Lip1 interacts with both the transmembrane region and the last luminal loop of Lac1 to maintain the proper acyl chain binding tunnel. A lateral opening on Lac1 serves as a potential entrance for the sphingoid base substrate. Our findings provide a template for understanding the working mechanism of eukaryotic ceramide synthases and may facilitate the development of therapeutic CerS modulators.

Structure and mechanism of a eukaryotic ceramide synthase complex.,Xie T, Fang Q, Zhang Z, Wang Y, Dong F, Gong X EMBO J. 2023 Dec 11;42(24):e114889. doi: 10.15252/embj.2023114889. Epub 2023 Nov , 13. PMID:37953642<ref>PMID:37953642</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 8izd" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae S288C]]
[[Category: Fang Q]]
[[Category: Gong X]]
[[Category: Xie T]]