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<StructureSection load='7stm' size='340' side='right'caption='[[7stm]], [[Resolution|resolution]] 3.02Å' scene=''> | <StructureSection load='7stm' size='340' side='right'caption='[[7stm]], [[Resolution|resolution]] 3.02Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
<table><tr><td colspan='2'>[[7stm]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7STM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7STM FirstGlance]. <br> | <table><tr><td colspan='2'>[[7stm]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Candida_albicans Candida albicans]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7STM OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7STM FirstGlance]. <br> | ||
</td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3PE:1,2-DIACYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>3PE</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=UD1:URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE'>UD1</scene | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.02Å</td></tr> | ||
<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=3PE:1,2-DIACYL-SN-GLYCERO-3-PHOSPHOETHANOLAMINE'>3PE</scene>, <scene name='pdbligand=MG:MAGNESIUM+ION'>MG</scene>, <scene name='pdbligand=UD1:URIDINE-DIPHOSPHATE-N-ACETYLGLUCOSAMINE'>UD1</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=7stm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7stm OCA], [https://pdbe.org/7stm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7stm RCSB], [https://www.ebi.ac.uk/pdbsum/7stm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7stm ProSAT]</span></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=7stm FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7stm OCA], [https://pdbe.org/7stm PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7stm RCSB], [https://www.ebi.ac.uk/pdbsum/7stm PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7stm ProSAT]</span></td></tr> | ||
</table> | </table> | ||
== Function == | |||
[https://www.uniprot.org/uniprot/CHS2_CANAX CHS2_CANAX] Polymerizes chitin, a structural polymer of the cell wall and septum, by transferring the sugar moiety of UDP-GlcNAc to the non-reducing end of the growing chitin polymer. | |||
<div style="background-color:#fffaf0;"> | <div style="background-color:#fffaf0;"> | ||
== Publication Abstract from PubMed == | == Publication Abstract from PubMed == | ||
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. | 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. | ||
Structural basis for inhibition and regulation of a chitin synthase from Candida albicans.,Ren Z, Chhetri A, Guan Z, Suo Y, Yokoyama K, Lee SY Nat Struct Mol Biol. 2022 Jul | Structural basis for inhibition and regulation of a chitin synthase from Candida albicans.,Ren Z, Chhetri A, Guan Z, Suo Y, Yokoyama K, Lee SY Nat Struct Mol Biol. 2022 Jul;29(7):653-664. doi: 10.1038/s41594-022-00791-x. , Epub 2022 Jul 4. PMID:35788183<ref>PMID:35788183</ref> | ||
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | ||
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__TOC__ | __TOC__ | ||
</StructureSection> | </StructureSection> | ||
[[Category: | [[Category: Candida albicans]] | ||
[[Category: Large Structures]] | [[Category: Large Structures]] | ||
[[Category: Chhetri | [[Category: Chhetri A]] | ||
[[Category: Lee | [[Category: Lee S]] | ||
[[Category: Ren | [[Category: Ren Z]] | ||
[[Category: Yokoyama | [[Category: Yokoyama K]] | ||
Latest revision as of 08:53, 5 June 2024
Chitin Synthase 2 from Candida albicans bound to UDP-GlcNAcChitin Synthase 2 from Candida albicans bound to UDP-GlcNAc
Structural highlights
FunctionCHS2_CANAX Polymerizes chitin, a structural polymer of the cell wall and septum, by transferring the sugar moiety of UDP-GlcNAc to the non-reducing end of the growing chitin polymer. Publication Abstract from PubMedChitin 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. Structural basis for inhibition and regulation of a chitin synthase from Candida albicans.,Ren Z, Chhetri A, Guan Z, Suo Y, Yokoyama K, Lee SY Nat Struct Mol Biol. 2022 Jul;29(7):653-664. doi: 10.1038/s41594-022-00791-x. , Epub 2022 Jul 4. PMID:35788183[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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