8e4z
From Proteopedia
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(New page: '''Unreleased structure''' The entry 8e4z is ON HOLD until Paper Publication Authors: Description: Category: Unreleased Structures) |
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| - | '''Unreleased structure''' | ||
| - | + | ==Co-crystal structure of Chaetomium glucosidase with compound 8== | |
| + | <StructureSection load='8e4z' size='340' side='right'caption='[[8e4z]], [[Resolution|resolution]] 2.37Å' scene=''> | ||
| + | == Structural highlights == | ||
| + | <table><tr><td colspan='2'>[[8e4z]] is a 2 chain structure with sequence from [https://en.wikipedia.org/wiki/Chaetomium_thermophilum_var._thermophilum_DSM_1495 Chaetomium thermophilum var. thermophilum DSM 1495]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=8E4Z OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8E4Z FirstGlance]. <br> | ||
| + | </td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">X-ray diffraction, [[Resolution|Resolution]] 2.37Å</td></tr> | ||
| + | <tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><scene name='pdbligand=BTB:2-[BIS-(2-HYDROXY-ETHYL)-AMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL'>BTB</scene>, <scene name='pdbligand=GOL:GLYCEROL'>GOL</scene>, <scene name='pdbligand=NAG:N-ACETYL-D-GLUCOSAMINE'>NAG</scene>, <scene name='pdbligand=SO4:SULFATE+ION'>SO4</scene>, <scene name='pdbligand=UKF:(2~{R},3~{R},4~{R},5~{S})-1-[6-[[4-(5-cyclobutyl-1,2,4-oxadiazol-3-yl)-2-nitro-phenyl]amino]hexyl]-2-(hydroxymethyl)piperidine-3,4,5-triol'>UKF</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=8e4z FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8e4z OCA], [https://pdbe.org/8e4z PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8e4z RCSB], [https://www.ebi.ac.uk/pdbsum/8e4z PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8e4z ProSAT]</span></td></tr> | ||
| + | </table> | ||
| + | == Function == | ||
| + | [https://www.uniprot.org/uniprot/G0SFD1_CHATD G0SFD1_CHATD] | ||
| + | <div style="background-color:#fffaf0;"> | ||
| + | == Publication Abstract from PubMed == | ||
| + | Enveloped viruses depend on the host endoplasmic reticulum (ER) quality control (QC) machinery for proper glycoprotein folding. The endoplasmic reticulum quality control (ERQC) enzyme alpha-glucosidase I (alpha-GluI) is an attractive target for developing broad-spectrum antivirals. We synthesized 28 inhibitors designed to interact with all four subsites of the alpha-GluI active site. These inhibitors are derivatives of the iminosugars 1-deoxynojirimycin (1-DNJ) and valiolamine. Crystal structures of ER alpha-GluI bound to 25 1-DNJ and three valiolamine derivatives revealed the basis for inhibitory potency. We established the structure-activity relationship (SAR) and used the Site Identification by Ligand Competitive Saturation (SILCS) method to develop a model for predicting alpha-GluI inhibition. We screened the compounds against SARS-CoV-2 in vitro to identify those with greater antiviral activity than the benchmark alpha-glucosidase inhibitor UV-4. These host-targeting compounds are candidates for investigation in animal models of SARS-CoV-2 and for testing against other viruses that rely on ERQC for correct glycoprotein folding. | ||
| - | + | Structure-Based Design of Potent Iminosugar Inhibitors of Endoplasmic Reticulum alpha-Glucosidase I with Anti-SARS-CoV-2 Activity.,Karade SS, Franco EJ, Rojas AC, Hanrahan KC, Kolesnikov A, Yu W, MacKerell AD Jr, Hill DC, Weber DJ, Brown AN, Treston AM, Mariuzza RA J Med Chem. 2023 Feb 23;66(4):2744-2760. doi: 10.1021/acs.jmedchem.2c01750. Epub , 2023 Feb 10. PMID:36762932<ref>PMID:36762932</ref> | |
| - | + | From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.<br> | |
| - | [[Category: | + | </div> |
| + | <div class="pdbe-citations 8e4z" style="background-color:#fffaf0;"></div> | ||
| + | == References == | ||
| + | <references/> | ||
| + | __TOC__ | ||
| + | </StructureSection> | ||
| + | [[Category: Chaetomium thermophilum var. thermophilum DSM 1495]] | ||
| + | [[Category: Large Structures]] | ||
| + | [[Category: Karade SS]] | ||
| + | [[Category: Mariuzza RA]] | ||
Current revision
Co-crystal structure of Chaetomium glucosidase with compound 8
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