+Open data
-Basic information
Entry | Database: PDB / ID: 7xe4 | ||||||
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Title | structure of a membrane-bound glycosyltransferase | ||||||
Components | 1,3-beta-glucan synthase component FKS1 | ||||||
Keywords | TRANSFERASE / membrane protein / glycosyltransferase | ||||||
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 / fungal-type cell wall biogenesis / cellular bud / ascospore wall assembly / cellular bud tip / fungal-type cell wall ...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 / fungal-type cell wall biogenesis / cellular bud / ascospore wall assembly / cellular bud tip / fungal-type cell wall / actin cortical patch / cellular bud neck / regulation of cell size / positive regulation of endocytosis / cell periphery / mitochondrion / plasma membrane Similarity search - Function | ||||||
Biological species | Saccharomyces cerevisiae (brewer's yeast) | ||||||
Method | ELECTRON MICROSCOPY / single particle reconstruction / cryo EM / Resolution: 3.4 Å | ||||||
Authors | Hu, X.L. / Yang, P. / Zhang, M. / Liu, X.T. / Yu, H.J. | ||||||
Funding support | China, 1items
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Citation | Journal: Nature / Year: 2023 Title: Structural and mechanistic insights into fungal β-1,3-glucan synthase FKS1. Authors: Xinlin Hu / Ping Yang / Changdong Chai / Jia Liu / Huanhuan Sun / Yanan Wu / Mingjie Zhang / Min Zhang / Xiaotian Liu / Hongjun Yu / Abstract: The membrane-integrated synthase FKS is involved in the biosynthesis of β-1,3-glucan, the core component of the fungal cell wall. FKS is the target of widely prescribed antifungal drugs, including ...The membrane-integrated synthase FKS is involved in the biosynthesis of β-1,3-glucan, the core component of the fungal cell wall. FKS is the target of widely prescribed antifungal drugs, including echinocandin and ibrexafungerp. 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 β-1,3-glucan biosynthesis and establish a foundation for developing new antifungal drugs by targeting FKS. | ||||||
History |
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-Structure visualization
Structure viewer | Molecule: MolmilJmol/JSmol |
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-Downloads & links
-Download
PDBx/mmCIF format | 7xe4.cif.gz | 289.9 KB | Display | PDBx/mmCIF format |
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PDB format | pdb7xe4.ent.gz | 231.8 KB | Display | PDB format |
PDBx/mmJSON format | 7xe4.json.gz | Tree view | PDBx/mmJSON format | |
Others | Other downloads |
-Validation report
Summary document | 7xe4_validation.pdf.gz | 1 MB | Display | wwPDB validaton report |
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Full document | 7xe4_full_validation.pdf.gz | 1.1 MB | Display | |
Data in XML | 7xe4_validation.xml.gz | 49.2 KB | Display | |
Data in CIF | 7xe4_validation.cif.gz | 74.3 KB | Display | |
Arichive directory | https://data.pdbj.org/pub/pdb/validation_reports/xe/7xe4 ftp://data.pdbj.org/pub/pdb/validation_reports/xe/7xe4 | HTTPS FTP |
-Related structure data
Related structure data | 33154MC 7yuyC M: map data used to model this data C: citing same article (ref.) |
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Similar structure data | Similarity search - Function & homologyF&H Search |
-Links
-Assembly
Deposited unit |
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1 |
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-Components
-Protein / Sugars , 2 types, 2 molecules F
#1: Protein | Mass: 215076.156 Da / Num. of mol.: 1 / Source method: isolated from a natural source / Source: (natural) Saccharomyces cerevisiae (brewer's yeast) / Strain: ATCC 204508 / S288c / References: UniProt: P38631, 1,3-beta-glucan synthase |
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#2: Polysaccharide | 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose |
-Non-polymers , 6 types, 25 molecules
#3: Chemical | ChemComp-DD9 / #4: Chemical | ChemComp-D10 / #5: Chemical | ChemComp-C14 / | #6: Chemical | ChemComp-HP6 / #7: Chemical | #8: Chemical | ChemComp-XKP / ( | |
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-Details
Has ligand of interest | N |
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-Experimental details
-Experiment
Experiment | Method: ELECTRON MICROSCOPY |
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EM experiment | Aggregation state: PARTICLE / 3D reconstruction method: single particle reconstruction |
-Sample preparation
Component | Name: membrane-bound glycosyltransferase / Type: COMPLEX / Entity ID: #1 / Source: NATURAL |
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Molecular weight | Value: 0.215 MDa / Experimental value: NO |
Source (natural) | Organism: Saccharomyces cerevisiae (brewer's yeast) |
Buffer solution | pH: 7.4 |
Specimen | Embedding applied: NO / Shadowing applied: NO / Staining applied: NO / Vitrification applied: YES |
Vitrification | Cryogen name: ETHANE |
-Electron microscopy imaging
Experimental equipment | Model: Titan Krios / Image courtesy: FEI Company |
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Microscopy | Model: FEI TITAN KRIOS |
Electron gun | Electron source: FIELD EMISSION GUN / Accelerating voltage: 300 kV / Illumination mode: FLOOD BEAM |
Electron lens | Mode: BRIGHT FIELD / Nominal defocus max: 3000 nm / Nominal defocus min: 1100 nm |
Image recording | Electron dose: 50 e/Å2 / Film or detector model: GATAN K3 (6k x 4k) |
-Processing
Software | Name: PHENIX / Version: 1.19.1_4122: / Classification: refinement | ||||||||||||||||||||||||
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CTF correction | Type: PHASE FLIPPING AND AMPLITUDE CORRECTION | ||||||||||||||||||||||||
3D reconstruction | Resolution: 3.4 Å / Resolution method: FSC 0.143 CUT-OFF / Num. of particles: 267574 / Symmetry type: POINT | ||||||||||||||||||||||||
Refine LS restraints |
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