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- EMDB-66419: Cryo-EM structure of Fks2 with intact active site -

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Basic information

Entry
Database: EMDB / ID: EMD-66419
TitleCryo-EM structure of Fks2 with intact active site
Map data
Sample
  • Cell: Cryo-EM structure of Fks1 in apo state
    • Protein or peptide: 1,3-beta-glucan synthase component GSC2
  • Ligand: ERGOSTEROL
  • Ligand: Enfumafungin
  • Ligand: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate
Keywordsenfumafungin / 1 / 3-beta-glucan synthase component GSC2 / MEMBRANE PROTEIN
Function / homology
Function and homology information


fungal-type cell wall polysaccharide biosynthetic process / 1,3-beta-glucan synthase / 1,3-beta-D-glucan synthase activity / (1->3)-beta-D-glucan biosynthetic process / 1,3-beta-D-glucan synthase complex / prospore membrane / ascospore wall assembly / cellular bud neck / cell periphery / membrane / plasma membrane
Similarity search - Function
: / 1,3-beta-glucan synthase component FKS1, second domain / Glycosyl transferase, family 48 / 1,3-beta-glucan synthase subunit FKS1-like, domain-1 / 1,3-beta-glucan synthase component / 1,3-beta-glucan synthase subunit FKS1, domain-1 / 1,3-beta-glucan synthase subunit FKS1
Similarity search - Domain/homology
1,3-beta-glucan synthase component GSC2
Similarity search - Component
Biological speciesSaccharomyces cerevisiae (brewer's yeast) / Saccharomyces cerevisiae S288C (yeast)
Methodsingle particle reconstruction / cryo EM / Resolution: 3.41 Å
AuthorsWang LX / Bai L
Funding support China, 1 items
OrganizationGrant numberCountry
National Natural Science Foundation of China (NSFC)32171212 China
CitationJournal: Nat Commun / Year: 2026
Title: Inhibition mechanism of the fungal β-1,3-glucan synthases by triterpenoid antifungal drugs.
Authors: Zi-Long You / Lei Sun / Le-Xuan Wang / Yue-Ran Ni / Rui-Qing Lyu / Dan-Dan Chen / Cai-Hong Yun / Tiefeng Song / Yinggai Song / Lin Bai /
Abstract: β-1,3-glucan synthase is the molecular target for triterpenoid and echinocandin antifungal drugs in clinical. It catalyzes the formation of β-1,3-glucan, which is the primary component of the ...β-1,3-glucan synthase is the molecular target for triterpenoid and echinocandin antifungal drugs in clinical. It catalyzes the formation of β-1,3-glucan, which is the primary component of the fungal cell wall. However, the inhibition mechanism of β-1,3-glucan synthase by triterpenoid drugs remains unclear. In this study, we report cryo-electron microscopy (cryo-EM) structures of Saccharomyces cerevisiae β-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 β-1,3-glucan synthases. Remarkably, the enfumafungin attaches on a single transmembrane helix TM5 of the β-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 β-1,3-glucan synthase.
History
DepositionSep 29, 2025-
Header (metadata) releaseFeb 18, 2026-
Map releaseFeb 18, 2026-
UpdateFeb 18, 2026-
Current statusFeb 18, 2026Processing site: PDBc / Status: Released

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Structure visualization

Supplemental images

emd_66419.png

Downloads & links

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Map

FileDownload / File: emd_66419.map.gz / Format: CCP4 / Size: 512 MB / Type: IMAGE STORED AS FLOATING POINT NUMBER (4 BYTES)
Projections & slices

Image control

Size
Brightness
Contrast
Others
AxesZ (Sec.)Y (Row.)X (Col.)
0.74 Å/pix.
x 512 pix.
= 378.88 Å		0.74 Å/pix.
x 512 pix.
= 378.88 Å		0.74 Å/pix.
x 512 pix.
= 378.88 Å

Surface

Projections

Slices (1/3)

Slices (1/2)

Slices (2/3)

Images are generated by Spider.

Voxel sizeX=Y=Z: 0.74 Å
Density

Histogram

Histogram (log scale)
Contour LevelBy AUTHOR: 0.15
Minimum - Maximum-0.42921987 - 0.625406
Average (Standard dev.)-0.000025517009 (±0.017549809)
SymmetrySpace group: 1
Details

EMDB XML:

Map geometry
Axis orderXYZ
Origin000
Dimensions512512512
Spacing512512512
CellA=B=C: 378.88 Å
α=β=γ: 90.0 °

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Supplemental data

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Half map: #2

Fileemd_66419_half_map_1.map
Projections & Slices
AxesZYX

Projections

Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Half map: #1

Fileemd_66419_half_map_2.map
Projections & Slices
AxesZYX

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Slices (1/2)
Density Histograms

Histogram

Histogram (log scale)

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Sample components

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Entire : Cryo-EM structure of Fks1 in apo state

EntireName: Cryo-EM structure of Fks1 in apo state
Components
  • Cell: Cryo-EM structure of Fks1 in apo state
    • Protein or peptide: 1,3-beta-glucan synthase component GSC2
  • Ligand: ERGOSTEROL
  • Ligand: Enfumafungin
  • Ligand: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate

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Supramolecule #1: Cryo-EM structure of Fks1 in apo state

SupramoleculeName: Cryo-EM structure of Fks1 in apo state / type: cell / ID: 1 / Parent: 0 / Macromolecule list: #1
Source (natural)Organism: Saccharomyces cerevisiae (brewer's yeast)

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Macromolecule #1: 1,3-beta-glucan synthase component GSC2

MacromoleculeName: 1,3-beta-glucan synthase component GSC2 / type: protein_or_peptide / ID: 1 / Number of copies: 1 / Enantiomer: LEVO / EC number: 1,3-beta-glucan synthase
Source (natural)Organism: Saccharomyces cerevisiae S288C (yeast)
Molecular weightTheoretical: 217.214875 KDa
Recombinant expressionOrganism: Saccharomyces cerevisiae (brewer's yeast)
SequenceString: MSYNDPNLNG QYYSNGDGTG DGNYPTYQVT QDQSAYDEYG QPIYTQNQLD DGYYDPNEQY VDGTQFPQGQ DPSQDQGPYN NDASYYNQP PNMMNPSSQD GENFSDFSSY GPPSGTYPND QYTPSQMSYP DQDGSSGAST PYGNGVVNGN GQYYDPNAIE M ALPNDPYP ...String:
MSYNDPNLNG QYYSNGDGTG DGNYPTYQVT QDQSAYDEYG QPIYTQNQLD DGYYDPNEQY VDGTQFPQGQ DPSQDQGPYN NDASYYNQP PNMMNPSSQD GENFSDFSSY GPPSGTYPND QYTPSQMSYP DQDGSSGAST PYGNGVVNGN GQYYDPNAIE M ALPNDPYP AWTADPQSPL PIEQIEDIFI DLTNKFGFQR DSMRNMFDHF MTLLDSRSSR MSPEQALLSL HADYIGGDTA NY KKWYFAA QLDMDDEIGF RNMKLGKLSR KARKAKKKNK KAMQEASPED TEETLNQIEG DNSLEAADFR WKSKMNQLSP FEM VRQIAL FLLCWGEANQ VRFTPECLCF IYKCASDYLD SAQCQQRPDP LPEGDFLNRV ITPLYRFIRS QVYEIVDGRY VKSE KDHNK VIGYDDVNQL FWYPEGIAKI VMEDGTRLID LPAEERYLKL GEIPWDDVFF KTYKETRSWL HLVTNFNRIW IMHIS VYWM YCAYNAPTFY THNYQQLVDN QPLAAYKWAT AALGGTVASL IQVAATLCEW SFVPRKWAGA QHLSRRFWFL CVIMGI NLG PVIFVFAYDK DTVYSTAAHV VGAVMFFVAV ATLVFFSVMP LGGLFTSYMK KSTRSYVASQ TFTASFAPLH GLDRWMS YL VWVTVFAAKY AESYFFLILS LRDPIRILST TSMRCTGEYW WGNKICKVQP KIVLGLMIAT DFILFFLDTY LWYIVVNT V FSVGKSFYLG ISILTPWRNI FTRLPKRIYS KILATTDMEI KYKPKVLISQ IWNAIIISMY REHLLAIDHV QKLLYHQVP SEIEGKRTLR APTFFVSQDD NNFETEFFPR DSEAERRISF FAQSLSTPIP EPLPVDNMPT FTVLTPHYAE RILLSLREII REDDQFSRV TLLEYLKQLH PVEWDCFVKD TKILAEETAA YENNEDEPEK EDALKSQIDD LPFYCIGFKS AAPEYTLRTR I WASLRSQT LYRTISGFMN YSRAIKLLYR VENPEIVQMF GGNADGLERE LEKMARRKFK FLVSMQRLAK FKPHELENAE FL LRAYPDL QIAYLDEEPP LNEGEEPRIY SALIDGHCEI LENGRRRPKF RVQLSGNPIL GDGKSDNQNH ALIFYRGEYI QLI DANQDN YLEECLKIRS VLAEFEELGI EQIHPYTPGL KYEDQSTNHP VAIVGAREYI FSENSGVLGD VAAGKEQTFG TLFA RTLAQ IGGKLHYGHP DFINATFMTT RGGVSKAQKG LHLNEDIYAG MNAVLRGGRI KHCEYYQCGK GRDLGFGTIL NFTTK IGAG MGEQMLSREY YYLGTQLPID RFLTFYYAHP GFHLNNLFIQ LSLQMFMLTL VNLHALAHES ILCVYDRDKP ITDVLY PIG CYNFHPAIDW VRRYTLSIFI VFWIAFVPIV VQELIERGLW KATQRFFRHI LSLSPMFEVF AGQIYSSALL SDIAVGG AR YISTGRGFAT SRIPFSILYS RFAGSAIYMG SRSMLMLLFG TVAHWQAPLL WFWASLSALI FAPFIFNPHQ FAWEDFFL D YRDYIRWLSR GNNKYHRNSW IGYVRMSRSR VTGFKRKLVG DESEKSAGDA SRAHRTNLIM AEIIPCAIYA AGCFIAFTF INAQTGVKTT DEDRVNSTLR IIICTLAPIV IDIGVLFFCM GLSCCSGPLL GMCCKKTGSV MAGIAHGIAV VVHIVFFIVM WVLEGFSFV RMLIGVVTCI QCQRLIFHCM TVLLLTREFK NDHANTAFWT GKWYSTGLGY MAWTQPTREL TAKVIELSEF A ADFVLGHV ILIFQLPVIC IPKIDKFHSI MLFWLKPSRQ IRPPIYSLKQ ARLRKRMVRR YCSLYFLVLI IFAGCIVGPA VA SAHVPKD LGSGLTGTFH NLVQPRNVSN NDTGSQMSTY KSHYYTHTPS LKTWSTIK

UniProtKB: 1,3-beta-glucan synthase component GSC2

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Macromolecule #3: ERGOSTEROL

MacromoleculeName: ERGOSTEROL / type: ligand / ID: 3 / Number of copies: 20 / Formula: ERG
Molecular weightTheoretical: 396.648 Da
Chemical component information

ChemComp-ERG:
ERGOSTEROL

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Macromolecule #4: Enfumafungin

MacromoleculeName: Enfumafungin / type: ligand / ID: 4 / Number of copies: 1 / Formula: A1E06
Molecular weightTheoretical: 708.876 Da

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Macromolecule #5: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(tri...

MacromoleculeName: (2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate
type: ligand / ID: 5 / Number of copies: 1 / Formula: POV
Molecular weightTheoretical: 760.076 Da
Chemical component information

ChemComp-POV:
(2S)-3-(hexadecanoyloxy)-2-[(9Z)-octadec-9-enoyloxy]propyl 2-(trimethylammonio)ethyl phosphate / phospholipid*YM

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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: 7.4
VitrificationCryogen name: ETHANE

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Electron microscopy

MicroscopeFEI TECNAI F30
Image recordingFilm or detector model: FEI FALCON IV (4k x 4k) / Average electron dose: 40.0 e/Å2
Electron beamAcceleration voltage: 200 kV / Electron source: FIELD EMISSION GUN
Electron opticsIllumination mode: FLOOD BEAM / Imaging mode: BRIGHT FIELD / Nominal defocus max: 1.8 µm / Nominal defocus min: 0.8 µm
Experimental equipment
Model: Tecnai F30 / Image courtesy: FEI Company

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Image processing

CTF correctionType: PHASE FLIPPING AND AMPLITUDE CORRECTION
Startup modelType of model: NONE
Final reconstructionResolution.type: BY AUTHOR / Resolution: 3.41 Å / Resolution method: FSC 0.143 CUT-OFF / Software - Name: cryoSPARC (ver. 4.6.0) / Number images used: 34524
Initial angle assignmentType: RANDOM ASSIGNMENT
Final angle assignmentType: ANGULAR RECONSTITUTION

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