8ele: Difference between revisions

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 <table><tr><td colspan='2'>[[8ele]] 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=8ELE OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=8ELE 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]] 2.6&#8491;</td></tr>
-<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=WM0:(2R,3R,4R,5S)-2-(hydroxymethyl)-1-{[4-({2-nitro-4-[(1R,5S)-3-oxa-8-azabicyclo[3.2.1]octan-8-yl]anilino}methyl)phenyl]methyl}piperidine-3,4,5-triol'>WM0</scene></td></tr>
+<tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat" id="ligandDat"><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=WM0:(2~{R},3~{R},4~{R},5~{S})-2-(hydroxymethyl)-1-[[4-[[[2-nitro-4-[(1~{R},5~{S})-3-oxa-8-azabicyclo[3.2.1]octan-8-yl]phenyl]amino]methyl]phenyl]methyl]piperidine-3,4,5-triol'>WM0</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=8ele FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=8ele OCA], [https://pdbe.org/8ele PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=8ele RCSB], [https://www.ebi.ac.uk/pdbsum/8ele PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=8ele ProSAT]</span></td></tr>
 </table>
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 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 10. doi: 10.1021/acs.jmedchem.2c01750. PMID:36762932<ref>PMID:36762932</ref>
+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&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>