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Open data
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Basic information
Entry | ![]() | |||||||||
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Title | Chitin Synthase 2 from Candida albicans bound to UDP-GlcNAc | |||||||||
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![]() | chitin synthesis / glycosyltransferase / membrane protein / TRANSFERASE | |||||||||
Function / homology | ![]() chitin synthase / chitin synthase activity / : / cell septum / cell periphery / membrane Similarity search - Function | |||||||||
Biological species | ![]() | |||||||||
Method | single particle reconstruction / cryo EM / Resolution: 3.02 Å | |||||||||
![]() | Ren Z / Chhetri A / Lee S / Yokoyama K | |||||||||
Funding support | 1 items
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![]() | ![]() Title: Structural basis for inhibition and regulation of a chitin synthase from Candida albicans. Authors: Zhenning Ren / Abhishek Chhetri / Ziqiang Guan / Yang Suo / Kenichi Yokoyama / Seok-Yong Lee / ![]() Abstract: Chitin is an essential component of the fungal cell wall. Chitin synthases (Chss) catalyze chitin formation and translocation across the membrane and are targets of antifungal agents, including ...Chitin is an essential component of the fungal cell wall. Chitin synthases (Chss) catalyze chitin formation and translocation across the membrane and are targets of antifungal agents, including nikkomycin Z and polyoxin D. Lack of structural insights into the action of these inhibitors on Chs has hampered their further development to the clinic. We present the cryo-EM structures of Chs2 from Candida albicans (CaChs2) in the apo, substrate-bound, nikkomycin Z-bound, and polyoxin D-bound states. CaChs2 adopts a unique domain-swapped dimer configuration where a conserved motif in the domain-swapped region controls enzyme activity. CaChs2 has a dual regulation mechanism where the chitin translocation tunnel is closed by the extracellular gate and plugged by a lipid molecule in the apo state to prevent non-specific leak. Analyses of substrate and inhibitor binding provide insights into the chemical logic of Chs inhibition, which can guide Chs-targeted antifungal development. | |||||||||
History |
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Structure visualization
Supplemental images |
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Downloads & links
-EMDB archive
Map data | ![]() | 34.8 MB | ![]() | |
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Header (meta data) | ![]() ![]() | 11.1 KB 11.1 KB | Display Display | ![]() |
Images | ![]() | 14.7 KB | ||
Filedesc metadata | ![]() | 5.9 KB | ||
Archive directory | ![]() ![]() | HTTPS FTP |
-Related structure data
Related structure data | ![]() 7stmMC ![]() 7stlC ![]() 7stnC ![]() 7stoC M: atomic model generated by this map C: citing same article ( |
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Similar structure data | Similarity search - Function & homology ![]() |
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Links
EMDB pages | ![]() ![]() |
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Related items in Molecule of the Month |
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Map
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Voxel size | X=Y=Z: 1.08 Å | ||||||||||||||||||||
Density |
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Symmetry | Space group: 1 | ||||||||||||||||||||
Details | EMDB XML:
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-Supplemental data
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Sample components
-Entire : Chitin synthase 2 from Candida albicans bound to UDP-GlcNAc
Entire | Name: Chitin synthase 2 from Candida albicans bound to UDP-GlcNAc |
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Components |
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-Supramolecule #1: Chitin synthase 2 from Candida albicans bound to UDP-GlcNAc
Supramolecule | Name: Chitin synthase 2 from Candida albicans bound to UDP-GlcNAc type: complex / ID: 1 / Parent: 0 / Macromolecule list: #1 |
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Source (natural) | Organism: ![]() |
-Macromolecule #1: Chitin synthase
Macromolecule | Name: Chitin synthase / type: protein_or_peptide / ID: 1 / Number of copies: 2 / Enantiomer: LEVO / EC number: chitin synthase |
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Source (natural) | Organism: ![]() |
Molecular weight | Theoretical: 119.298227 KDa |
Recombinant expression | Organism: ![]() ![]() |
Sequence | String: MSYNNPNNSN SHLRPHAYNN SRRDDSDGDE SSIEFLNQRS NTPLTQGTYN YHNTSTNSLN FQQPEPIYRN QTRTSLSDSY YDHPIFDTS QTQIQPPHDN PFTESYEMTD TSYQGNDHHY RTGQPNHLMN PTYNQAFIPH VYDEEDNDEQ EYDQRIQYNQ F QGDHFDLA ...String: MSYNNPNNSN SHLRPHAYNN SRRDDSDGDE SSIEFLNQRS NTPLTQGTYN YHNTSTNSLN FQQPEPIYRN QTRTSLSDSY YDHPIFDTS QTQIQPPHDN PFTESYEMTD TSYQGNDHHY RTGQPNHLMN PTYNQAFIPH VYDEEDNDEQ EYDQRIQYNQ F QGDHFDLA AISYADDESQ SQLDYVPTER VIPEGEEEEE EGETSFEKEP GSETISGPFG EERSFEEPPP QQEVRSKKLT RA TGLNGHL VLDCPVADEL LSKFPDYNPA EKSGGLSREF AFMRYTAVTC GPSNFYRDAY ILRPVHYPIP RQTELMIVIT MYN EDDILL GRTLKGVFKN IKYLESKARS STWGKDSWKK IVVCIVSDGR TKINERAQAL LAGLGVYQEG LAKSRVDDKK VQAH MFEYT TRVGISKVTD DVVKLTTEKV VPVQMLFCLK ETNAKKINSH RWCFQAIGQV LDPKIVVLLD CGTQPSGRSL YELWK EFDR DHRVAGACGE ITTSLKKRQM ITNPLVYGQN FEYKISNILD KPTESSFGFI SVLPGAFSAY RFIALQNDIN GVGPLE KYF KGEFLHSSGE LDPNDDEFQM KHLMLKEEAG IFTSNMYLAE DRILCFELVA KRGCNWLLRY CKSARAETDV PEGLAEF IL QRRRWLNGSF FAAIYSLVHF YKVWTSSHSF GRKIFLHIEF FYQLINLIVS WFSIGSYFLV FRILTTSLGD KALGFAPG K ILSVIFLWLY LASIVTTFVL SFGNKPKGTE KFYVTIVIFF AILMAYMIFA AIFMAVHSIQ DIYRSGTRIT VSLFFQNSE FRDLVVATSS TYALYFLASF LYFEPWHMFT SFVQYILLSP SYVNVLNIYA FCNIDDISWG TKGEVGGKSL GEAKLREDGT FDVSVPISK EQINQSYLDQ LEKIRDPAPP EEKVLVTNTE DYYAFIRSMT VLVWMFTNFV VIALVLETGG FNQFVEATDL A NLKSNRAA VFLTVILWTV AFMALFRFIG CIYYLITRLG REIKASEHAT KANSLEVLFQ GPDYKDDDDK AHHHHHHHHH H UniProtKB: chitin synthase |
-Macromolecule #2: 1,2-Distearoyl-sn-glycerophosphoethanolamine
Macromolecule | Name: 1,2-Distearoyl-sn-glycerophosphoethanolamine / type: ligand / ID: 2 / Number of copies: 8 / Formula: 3PE |
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Molecular weight | Theoretical: 748.065 Da |
Chemical component information | ![]() ChemComp-3PE: |
-Macromolecule #3: MAGNESIUM ION
Macromolecule | Name: MAGNESIUM ION / type: ligand / ID: 3 / Number of copies: 2 / Formula: MG |
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Molecular weight | Theoretical: 24.305 Da |
-Macromolecule #4: URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE
Macromolecule | Name: URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE / type: ligand / ID: 4 / Number of copies: 2 / Formula: UD1 |
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Molecular weight | Theoretical: 607.354 Da |
Chemical component information | ![]() ChemComp-UD1: |
-Experimental details
-Structure determination
Method | cryo EM |
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![]() | single particle reconstruction |
Aggregation state | particle |
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Sample preparation
Buffer | pH: 7.5 |
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Vitrification | Cryogen name: ETHANE |
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Electron microscopy
Microscope | FEI TITAN KRIOS |
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Image recording | Film or detector model: GATAN K3 (6k x 4k) / Average electron dose: 60.0 e/Å2 |
Electron beam | Acceleration voltage: 300 kV / Electron source: ![]() |
Electron optics | Illumination mode: SPOT SCAN / Imaging mode: BRIGHT FIELD / Nominal defocus max: 2.0 µm / Nominal defocus min: 1.0 µm |
Experimental equipment | ![]() Model: Titan Krios / Image courtesy: FEI Company |
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Image processing
Startup model | Type of model: OTHER / Details: From Ab initio |
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Final reconstruction | Applied symmetry - Point group: C2 (2 fold cyclic) / Resolution.type: BY AUTHOR / Resolution: 3.02 Å / Resolution method: FSC 0.143 CUT-OFF / Number images used: 287321 |
Initial angle assignment | Type: MAXIMUM LIKELIHOOD |
Final angle assignment | Type: MAXIMUM LIKELIHOOD |