View source for 7xe4


==structure of a membrane-bound glycosyltransferase==
<StructureSection load='7xe4' size='340' side='right'caption='[[7xe4]], [[Resolution|resolution]] 3.40&Aring;' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[7xe4]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Saccharomyces_cerevisiae Saccharomyces cerevisiae]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7XE4 OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7XE4 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]] 3.4&#8491;</td></tr>
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=C14:TETRADECANE'>C14</scene>, <scene name='pdbligand=D10:DECANE'>D10</scene>, <scene name='pdbligand=D12:DODECANE'>D12</scene>, <scene name='pdbligand=DD9:NONANE'>DD9</scene>, <scene name='pdbligand=HP6:HEPTANE'>HP6</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=XKP:(11R,14S)-17-amino-14-hydroxy-8,14-dioxo-9,13,15-trioxa-14lambda~5~-phosphaheptadecan-11-yl+decanoate'>XKP</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=7xe4 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7xe4 OCA], [https://pdbe.org/7xe4 PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7xe4 RCSB], [https://www.ebi.ac.uk/pdbsum/7xe4 PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7xe4 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 ==
The membrane-integrated synthase FKS is involved in the biosynthesis of beta-1,3-glucan, the core component of the fungal cell wall(1,2). FKS is the target of widely prescribed antifungal drugs, including echinocandin and ibrexafungerp(3,4). Unfortunately, the mechanism of action of FKS remains enigmatic and this has hampered development of more effective medicines targeting the enzyme. Here we present the cryo-electron microscopy structures of Saccharomyces cerevisiae FKS1 and the echinocandin-resistant mutant FKS1(S643P). These structures reveal the active site of the enzyme at the membrane-cytoplasm interface and a glucan translocation path spanning the membrane bilayer. Multiple bound lipids and notable membrane distortions are observed in the FKS1 structures, suggesting active FKS1-membrane interactions. Echinocandin-resistant mutations are clustered at a region near TM5-6 and TM8 of FKS1. The structure of FKS1(S643P) reveals altered lipid arrangements in this region, suggesting a drug-resistant mechanism of the mutant enzyme. The structures, the catalytic mechanism and the molecular insights into drug-resistant mutations of FKS1 revealed in this study advance the mechanistic understanding of fungal beta-1,3-glucan biosynthesis and establish a foundation for developing new antifungal drugs by targeting FKS.

Structural and mechanistic insights into fungal beta-1,3-glucan synthase FKS1.,Hu X, Yang P, Chai C, Liu J, Sun H, Wu Y, Zhang M, Zhang M, Liu X, Yu H Nature. 2023 Apr;616(7955):190-198. doi: 10.1038/s41586-023-05856-5. Epub 2023 , Mar 22. PMID:36949198<ref>PMID:36949198</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 7xe4" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Large Structures]]
[[Category: Saccharomyces cerevisiae]]
[[Category: Hu XL]]
[[Category: Liu XT]]
[[Category: Yang P]]
[[Category: Yu HJ]]
[[Category: Zhang M]]