View source for 9wy1


==Cryo-EM structure of Fks1 in apo state==
<StructureSection load='9wy1' size='340' side='right'caption='[[9wy1]], [[Resolution|resolution]] 3.23&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[9wy1]] is a 1 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=9WY1 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=9WY1 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]] 3.23&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=AV0:(2~{R},3~{R},4~{S},5~{S},6~{R})-2-[(2~{R},3~{S},4~{R},5~{R},6~{R})-6-[2-decyl-2-[[(2~{R},3~{R},4~{R},5~{S},6~{R})-6-(hydroxymethyl)-5-[(2~{R},3~{R},4~{S},5~{S},6~{R})-6-(hydroxymethyl)-3,4,5-tris(oxidanyl)oxan-2-yl]oxy-3,4-bis(oxidanyl)oxan-2-yl]oxymethyl]dodecoxy]-2-(hydroxymethyl)-4,5-bis(oxidanyl)oxan-3-yl]oxy-6-(hydroxymethyl)oxane-3,4,5-triol'>AV0</scene>, <scene name='pdbligand=ERG:ERGOSTEROL'>ERG</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=POV:(2S)-3-(HEXADECANOYLOXY)-2-[(9Z)-OCTADEC-9-ENOYLOXY]PROPYL+2-(TRIMETHYLAMMONIO)ETHYL+PHOSPHATE'>POV</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=9wy1 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=9wy1 OCA], [https://pdbe.org/9wy1 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=9wy1 RCSB], [https://www.ebi.ac.uk/pdbsum/9wy1 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=9wy1 ProSAT]</span></td></tr>
</table>
== Function ==
[https://www.uniprot.org/uniprot/FKS1_YEAST FKS1_YEAST] Alternate catalytic subunit of the 1,3-beta-glucan synthase (GS) complex. Synthesizes 1,3-beta-glucan, a major structural component of the yeast cell wall. Involved in cell wall synthesis, maintenance and remodeling.<ref>PMID:11856368</ref> 
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
beta-1,3-glucan synthase is the molecular target for triterpenoid and echinocandin antifungal drugs in clinical. It catalyzes the formation of beta-1,3-glucan, which is the primary component of the fungal cell wall. However, the inhibition mechanism of beta-1,3-glucan synthase by triterpenoid drugs remains unclear. In this study, we report cryo-electron microscopy (cryo-EM) structures of Saccharomyces cerevisiae beta-1,3-glucan synthase Fks1 and Fks2 in the apo state, the triterpenoid drug enfumafungin-bound state, and an open state. Structural analysis along with mutagenesis reveals the enfumafungin binding site, and the mechanism of the clinical drug-resistant mutations of the beta-1,3-glucan synthases. Remarkably, the enfumafungin attaches on a single transmembrane helix TM5 of the beta-1,3-glucan synthases, reorganizes its nearby lipid environment, and stabilizes the enzyme in a specific basal state with intact active site. Moreover, we elucidate that both the basal state and the open state are essential for FKS's glycosyltransferase activity. Our research also shows that Fks2 is highly conserved with Fks1 in terms of structure, activity, and drug inhibition. These findings provide deep insights into the fungal cell wall synthesis, and will facilitate the development of antifungal drugs targeting beta-1,3-glucan synthase.

Inhibition mechanism of the fungal beta-1,3-glucan synthases by triterpenoid antifungal drugs.,You ZL, Sun L, Wang LX, Ni YR, Lyu RQ, Chen DD, Yun CH, Song T, Song Y, Bai L Nat Commun. 2026 Feb 4. doi: 10.1038/s41467-026-69114-8. PMID:41639077<ref>PMID:41639077</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 9wy1" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae S288C]]
[[Category: Bai L]]
[[Category: You ZL]]