7sto
From Proteopedia
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<StructureSection load='7sto' size='340' side='right'caption='[[7sto]], [[Resolution|resolution]] 3.15Å' scene=''> | <StructureSection load='7sto' size='340' side='right'caption='[[7sto]], [[Resolution|resolution]] 3.15Å' scene=''> | ||
== Structural highlights == | == Structural highlights == | ||
| - | <table><tr><td colspan='2'>[[7sto]] is a 2 chain structure. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=7STO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7STO FirstGlance]. <br> | + | <table><tr><td colspan='2'>[[7sto]] 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=7STO OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=7STO 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=BJ9:1-{(2R,3R,4S,5R)-5-[(S)-{[(2S,3S,4S)-2-amino-5-(carbamoyloxy)-3,4-dihydroxypentanoyl]amino}(carboxy)methyl]-3,4-dihydroxyoxolan-2-yl}-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic+acid+(non-preferred+name)'>BJ9</scene | + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Electron Microscopy, [[Resolution|Resolution]] 3.15Å</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=BJ9:1-{(2R,3R,4S,5R)-5-[(S)-{[(2S,3S,4S)-2-amino-5-(carbamoyloxy)-3,4-dihydroxypentanoyl]amino}(carboxy)methyl]-3,4-dihydroxyoxolan-2-yl}-2,4-dioxo-1,2,3,4-tetrahydropyrimidine-5-carboxylic+acid+(non-preferred+name)'>BJ9</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=7sto FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sto OCA], [https://pdbe.org/7sto PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sto RCSB], [https://www.ebi.ac.uk/pdbsum/7sto PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sto 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=7sto FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=7sto OCA], [https://pdbe.org/7sto PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=7sto RCSB], [https://www.ebi.ac.uk/pdbsum/7sto PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=7sto 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]] |
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Current revision
Chitin Synthase 2 from Candida albicans bound to polyoxin D
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